Gynecologic Pathology

Condyloma acuminatum
Condyloma acuminatum
Vulvar lesion
Koilocytic atypia (or, koilocytic change)
Koilocytic atypia (or, koilocytic change)
– Enlarged cells with perinuclear cytoplasmic clearing (halos)
– Enlarged or pyknotic nuclei with irregular membranes (raisinoid)
– Binucleate and multinucleate forms are common
HPV 6 and 11
The most common types of HPV associated with condyloma acuminatum of the vulva
p16 INK4a
immunohistochemical stain that assists in excluding aggressive HPV types (e.g., 16, 18, 31, 45)
Most regress spontaneously
Typical clinical history of condyloma acuminatum of the vulva
HPV 16
Most common type of HPV associated with vulvar intraepithelial neoplasia
Vulvar erythroplasia of Queyrat
Vulvar erythroplasia of Queyrat
VIN lesions in mucous membranes of the vulvar vestibule that are often red
Vulvar lichen sclerosis et atrophicus
Vulvar lichen sclerosis et atrophicus
Extramammary Paget disease
Extramammary Paget disease
Vulvar biopsy
– Grade 1: no undifferentiated cells; keratin pearls
– Grade 2: less than 50% undifferentiated cells
– Grade 3: greater than 50% undifferentiated cells
Gynecologic Oncology Group (GOG) grade in vulvar invasive squamous cell carcinoma
Labia
In what part of the vulva does malignant melanoma most often arise?
“Melanoma is a disease of older women”
Most common demographic to have malignant melanoma of the vulva.
Bartholin gland carcinoma
Bartholin gland carcinoma
Vulvar lesion
Older women
Most common demographic to have Bartholin gland carcinoma
This is the adenoid cystic type of Bartholin gland carcinoma
This is the adenoid cystic type of Bartholin gland carcinoma
In which part of the vulva did this lesion arise?
Paget disease of the vulva
Fluorescein is useful in visualizing which vulvar neoplasm before excision of the same?
Uncommonly (10%-20%) associated with underlying malignancy
Mammary Paget disease is usually associated with an underlying malignancy (most commonly DCIS). How about vulvar Paget disease?
Vulvar Paget disease
Vulvar Paget disease
Pink to red eczematous patches with white foci due to hyperkeratosis
Vulvar Paget disease
Vulvar Paget disease
Vulvar biopsy:
– Abnormal cells in the epidermis concentrated in the basal layer but may also be present superficially and in skin appendages
– Intraepithelial tumor cells singly or in small groups
– Large cells with round nuclei often containing large nucleoli
– Pale cytoplasm or vacuolated signet ring cells
Vulvar Paget disease
Vulvar Paget disease
Which vulvar neoplasm has this IHC staining pattern with Her2/neu, CK7, low molecular weight cytokeratin, and CEA?
Generally not associated with HPV
HPV in vulvar Paget disease
Recurrences are frequent because lesions are often more extensive than can be appreciated clinically
Why are recurrences frequent in vulvar Paget disease?
Papillary hidradenoma
Papillary hidradenoma
Vulvar lesion
Papillary hidradenoma
Papillary hidradenoma
Vulvar lesion
Papillary hidradenoma. The papillary and tubular structures have an inner layer of columnar or cuboidal cells and a peripheral layer of myoepithelial cells.
Papillary hidradenoma. The papillary and tubular structures have an inner layer of columnar or cuboidal cells and a peripheral layer of myoepithelial cells.
Vulvar lesion
Papillary hidradenoma.
Papillary hidradenoma.
Vulvar lesion. High power view showing glandular structures which have morphologic and immunohistochemical similarities to the intraductal papilloma of the breast.
Angiomyofibroblastoma
Angiomyofibroblastoma
Vulvar lesion.Spindle-shaped tumor cells with perivascular distribution. A prominent perivascular chronic inflammatory infiltrate is noted.
– Benign spindle cell stroma
– Numerous small vessels
– Perivascular hypercellularity
– Mast cells are usually present
Histology of angiomyofibroblastoma of the vulva
– Vimentin and desmin positive
– Smooth muscle actin (SMA) negative
– S-100 protein negative
Immunophenotype of angiomyofibroblastoma of the vulva
Treated by local excision
Clinical behavior of angiomyofibroblastoma of the vulva
Differential diagnosis includes angiomyofibroblastoma and aggressive angiomyxoma
Differential diagnosis includes angiomyofibroblastoma and aggressive angiomyxoma
Angiomyofibroblastoma of the vulva
Angiomyofibroblastoma of the vulva
Vulvar lesion. Notice the prominent vasculature.
Aggressive angiomyxoma
Aggressive angiomyxoma
Prominent myxoid stroma with small blood vessels is evident in this lesion.
Aggressive angiomyxoma
Aggressive angiomyxoma
Mass in the vulvar region of a 22 year old woman
Aggressive angiomyxoma
Aggressive angiomyxoma
The tumor is composed of bland spindle cells with round or oval nuclei and scant or moderate eosinophilic cytoplasm distributed in a myxoid matrix.
Angiomyofibroblastoma of the vulva
Angiomyofibroblastoma of the vulva
Microscopically, it is composed of numerous thin-walled blood vessels and myofibroblasts in a collagenous matrix. It may have alternating zones of hypo and hypercellularity.
Women of reproductive age
Most common age group for angiomyofibroblastoma of the vulva
Angiomyofibroblastoma has the following features
– More cellular
– Well-defined tumor margins
– Lacks numerous clustered arterioles
Angiomyofibroblastoma of the vulva versus aggressive angiomyxoma an histology
Fibroepithelial polyp of the vagina
Fibroepithelial polyp of the vagina
Vaginal lesion
Soft polyp or papillary mass usually in the lower third of the vagina
Where in the vagina do fibroepithelial polyps tend to occur?
Reproductive-age females. It is hormonally sensitive and may be especially seen during pregnancy
Most common age group for fibroepithelial polyp of the vagina
Fibroepithelial polyp of the vagina
Fibroepithelial polyp of the vagina
Loose fibrovascular stroma underlying an unremarkable squamous mucosa
Fibroepithelial polyp of the vagina
Fibroepithelial polyp of the vagina
– Hormonally-induced localized hyperplasia of the subepithelial stroma.
– The stroma may be hypo- or hypercellular and may show bizarre stellate cells and brisk mitotic activity mimicking a sarcoma
Squamous papilloma
Squamous papilloma
Vaginal lesion. Papillary lesion lined by squamous epithelium.
Vaginal adenosis
Vaginal adenosis
Vaginal lesion. Low-power view demonstrates glandular epithelium at the junction of the mucosa and submucosa or lamina propria in the vagina
Associated with diethylstilbestrol (DES) exposure, most frequently in utero
Clinical scenario most common in vaginal adenosis
Vaginal adenosis
Vaginal adenosis
Clinical finding in a DES daughter
Vaginal adenosis
Vaginal adenosis
Vaginal lesion:
– Mucous columnar epithelium resembling endocervical mucosa replaces squamous lining of vagina
– Mucinous glands are present in the lamina propria
To prevent miscarriages
DES was prescribed to women in the 1940s and 1950s for what purpose?
Clear cell adenocarcinoma of the vagina
Mesonephroid adenocarcinoma of the vagina is the older term for _____.
Often but not always associated with in utero exposure to DES
Clear cell adenocarcinoma of the vagina is often (but not always) associated with what?
Clear cell adenocarcinoma of the vagina
Vaginal adenosis believed to be a precursor lesion of what malignancy?
Clear cell adenocarcinoma of the vagina
Clear cell adenocarcinoma of the vagina
The papillae are lined by large pleomorphic cells showing clear cytoplasm. Focal necrosis is present.
Clear cell adenocarcinoma of the vagina
Clear cell adenocarcinoma of the vagina
The image shows tubules, ductules, and cystic spaces lined by plump cells with clear or eosinophilic cytoplasm.
Clear cell adenocarcinoma of the vagina
Clear cell adenocarcinoma of the vagina
Rhabdomyoma
Rhabdomyoma
Benign vaginal mesenchymal neoplasm. Lack of cytologic atypia, lack of mitotic activity, and the absence of cambium layer .
About 25 case reports
How common is benign rhabdomyoma of the vagina?
Embryonal rhabdomyosarcoma (sarcoma botryoides)
Embryonal rhabdomyosarcoma (sarcoma botryoides)
Vaginal lesion. Superficial attenuated layer of squamous epithelium. Underlying cambium layer composed of small, round to spindled, primitive blue cells with dense hyperchromatic nuclei and minimal cytoplasm.
The sparsely cellular region underlying the cambium layer
Where are the cells with rhabdoid differentiation (the so called “strap cells”) found in a section of vaginal embryonal rhabdomyosarcoma?
– Desmin and muscle-specific actin (MSA) positive
– Myoglobin: more specific but less sensitive than above stains and therefore may be negative
– Vimentin positive in small and large tumor cells
– Cytokeratin negative (positive in benign overlying layer of attenuated epithelium)
IHC in vaginal rhabdomyosarcoma
Chronic endometritis
Chronic endometritis
Reactive changes on an endometrial biopsy from a woman with an IUD.
Simple hyperplasia
Simple hyperplasia
Grade the endometrial hyperplasia
Complex hyperplasia with atypia
Complex hyperplasia with atypia
Grade the endometrial hyperplasia
Inactivation of PTEN tumor suppressor gene is associated with the development of hyperplasia and related cancers
Which tumor suppressor gene is associated with endometrial hyperplasia?
Grade 1: less than 5% of the tumor is composed of solid areas
Grade 2: 5% to 50% of the tumor is composed of solid areas
Grade 3: greater than 50% of the tumor is composed of solid areas
FIGO grading of endometrial endometrioid carcinoma.
Clear cell carcinoma of the endometrium
Clear cell carcinoma of the endometrium
The tumor is composed of sheets of large cells with abundant clear cytoplasm.
Serous carcinoma of the endometrium
Serous carcinoma of the endometrium
Papillary structures lined by pleomorphic cells and invading the surrounding desmoplastic stroma.
– *H*emolytic anemia
– *E*levated *L*iver enzymes
– *L*ow *P*latelets
Symptoms in HELLP syndrome
Characteristic EM finding of dysgerminoma (also seen in seminoma and germinoma).
Characteristic EM finding of dysgerminoma (also seen in seminoma and germinoma).
Wandering (aka, reticular or meandering) nucleolus.
Postmenopausal white women
Postmenopausal white women
Most common patient population in which lichen sclerosus et atrophicus is seen in the vulva?
Histopathology of chronic atrophic vulvitis (lichen sclerosus et atrophicus)
Histopathology of chronic atrophic vulvitis (lichen sclerosus et atrophicus)
– Thinned epidermis with blunting of rete ridges
– Dermal edema or collagenization
– Scattered bandlike lymphocytes underlying abnormal dermis
Another name for lichen sclerosus et atrophicus
Chronic atrophic vulvitis synonym
Even though this is not recognized as a precancerous condition in and of itself, it is associated with a higher than average risk of developing subsequent vulvar carcinoma (1 to 4%) of patients
Cancer risk in lichen sclerosus of the vulva
Most commonly HPV types 6 and 11 (low risk serotypes)
Which types of HPV are associated with condyloma acuminatum of the vulva?
These lesions turn white
What happens to condyloma acuminatum upon application of 3% to 5% acetic acid under colposcopic examination?
– Less than 1 mm invasion below the basement membrane
– Less than 2 cm in greatest diameter
How is microinvasive squamous cell carcinoma of the vulva defined?
– No
– Extramammary Paget disease is a de novo disease either of the epidermis or the skin adnexa
Is extramammary Paget disease associated with underlying malignancy as is mammary Paget disease?
Histopathology of papillary hidradenoma of the vulva
Histopathology of papillary hidradenoma of the vulva
– Identical histology to intraductal papilloma of the breast
– Complex papillary structures showing fine fibrovascular cores and a collagenous stroma
– Inner layer of columnar or cuboidal cells
– Basal layer of flattened myoepithelial cells underlies the epithelium
– Middle aged woman
– 1 to 2 cm vulvar mass
Clinical presentation of papillary hidradenoma of the vulva
Histopathology of aggressive angiomyxoma
Histopathology of aggressive angiomyxoma
– Myxoid stroma with benign spindled fibroblasts and myofibroblasts
– Numerous clustered medium-sized arterioles
– Entrapped fat, neural elements, or glandular elements may be present
– Locally aggressive
– Metastases are rare
Clinical behavior of aggressive angiomyxoma
In utero diethylstilbestrol exposure
In utero diethylstilbestrol exposure
Clinical history associated with clear cell carcinoma of the vagina
Clear cell carcinoma
Clear cell carcinoma
Vaginal malignancy presenting in a “DES daughter”
Histopathology of clear cell carcinoma of the vulva
Histopathology of clear cell carcinoma of the vulva
– Tumor cells are polyhedral with round, atypical nuclei and clear cytoplasm containing glycogen
– Hobnail cell is a characteristic finding (cell with a nucleus that protrudes beyond the boundaries of the cell into a luminal, tubular, or cystic space)
Embryonal rhabdomyosarcoma
What is a synonym for sarcoma botryoides of the vagina?
Girls five years old or younger
Most common age at presentation of embryonal rhabdomyosarcoma (sarcoma botryoides) of the vagina?
Multigravidas during the fourth to sixth decades are the typical patients with polyps
Most common age distribution of an endocervical polyp
Histopathology of cervical polyp
Histopathology of cervical polyp
– Varying amounts of squamous or endocervical epithelium depending on proximity to cervical os
– Stroma consists of dense fibroconnective tissue with thin and thick-walled vessels
– Incidental finding in cervical specimens mostly in women of reproductive age
– May present with postcoital spotting or bleeding
– Associated with history of oral contraceptive use, pregnancy, or postpartum
Typical clinical presentation of microglandular hyperplasia of the cervix
Histopathology of microglandular hyperplasia of the cervix
Histopathology of microglandular hyperplasia of the cervix
• Single or multiple foci of crowded glands have variable amounts of mucin
• Variably sized glands include rare mitotic figures (1 mitotic figure/10 hpf)
• Uniform small round nuclei have even chromatin and some signet ring cells
• Focal squamous metaplasia may be present
• Neutrophils are commonly present in the glandular lumina
• Stroma separating the glands shows acute and chronic inflammatory cells
Microglandular hyperplasia
Name a benign, polypoid cervical lesion associated with oral contraceptive use.
HPV 16
Most common type of HPV seen in SIL is?
In utero diethylstilbestrol exposure.
Clear cell adenocarcinoma of the cervix is often associated with a history of exposure to which drug?
Histopathology of cervical clear cell carcinoma
Histopathology of cervical clear cell carcinoma
— Tubulocystic and solid are the most common patterns
— Papillary, tubular, and trabecular patterns may also be seen
— Tumor cells are polyhedral with round, atypical nuclei and clear cytoplasm containing glycogen
— The hobnail cell is a common and characteristic finding: cell in which the nucleus protrudes beyond the boundaries of the cell into the luminal, tubular, or cystic space
- Can present with post-menopausal bleeding - Benign lesion without any risk of progression to carcinoma - Treated with total hysterectomy to prevent local recurrence
– Can present with post-menopausal bleeding
– Benign lesion without any risk of progression to carcinoma
– Treated with total hysterectomy to prevent local recurrence
What is the clinical significance of adenofibroma of the uterus?
Histology of metastasis in carcinosarcoma of the uterus (also called metaplastic carcinoma of the uterus)
– Early metastases are epithelial
– Late metastases are both epithelial and spindle cell or exclusively spindle cell (sarcomatous overgrowth)
Histopathology of endometrial stromal nodules
Histopathology of endometrial stromal nodules
– Small uniform oval to spindled cells resembling endometrial stromal cells
– Minimal cytologic atypia and generally less than 10 mitotic figures/10 hpf
– Numerous thin-walled vessels evenly spaced among stromal cells and resembling spiral arterioles
– Rare small foci of necrosis, cystic degeneration, foam cells, calcification, decidualization, and sex cord-like structures
• CD10 positive
• Vimentin positive
• Reticulin positive surrounding individual cells
• Cytokeratin negative, except in sex cord elements
• SMA, desmin mostly negative except for stromal myoma
• Epithelial membrane antigen (EMA) negative
IHC in endometrial stromal tumor
– Endometrial stromal sarcoma has endolymphatic invasion.
– It was this histologic finding that inspired the older (now obsolete) name of endometrial stromal sarcoma: “endolymphatic stromal myosis””
What is the key histologic difference between endometrial stromal nodule and endometrial stromal sarcoma?
– The spindle cells around the glandular structures decorate with CD10
– This IHC pattern confirms that the spindle cells are endometrial stroma rather than smooth muscle (which would be concerning for invasion)
Immunohistochemistry in adenomyosis of the endometrium
– Invasive adenocarcinoma will demonstrate malignant glands surrounded by reactive, desmoplastic stroma, an inflammatory stromal response, or both
– Adenocarcinoma in adenomyosis will demonstrate malignant glands surrounded by unremarkable endometrial stroma (can demonstrate this with a CD10 IHC, which stains normal endometrial stroma)
What is the histologic difference between endometrial adenocarcinoma in situ involving adenomyosis and invasive adenocarcinoma?
- These are considered atypical variants - They should be reported out as smooth muscle tumors with uncertain malignant potential (STUMP)
– These are considered atypical variants
– They should be reported out as smooth muscle tumors with uncertain malignant potential (STUMP)
What is the clinical behavior of the epithelioid, bizarre (pictured), and intravenous types of leiomyomatosis?
Epithelioid leiomyoma
Epithelioid leiomyoma
Name the histologic variant of myometrial leiomyoma in this photomicrograph.
Intravenous leiomyomatosis
Intravenous leiomyomatosis
Name the histologic variant of myometrial leiomyoma in this photomicrograph.
Tumors in women older than 35 years of age that show mild cytologic atypia and more than 5 mitotic figures per 10 hpf
Histologic and clinical features that would put an otherwise typical leiomyoma into the “atypical, uncertain malignant potential” category
– Numerous follicular cysts in both ovaries
– Anovulation
– Infertility
– Hirsutism
– Oligomenorrhea
– Obesity
Clinical features of polycystic ovarian syndrome
Polycystic ovarian syndrome
Stein-Leventhal syndrome is a synonym for what?
– Most cases show an increased LH:FSH ratio
– Occasional cases will show hyperprolactinemia
Chemistry in polycystic ovarian (aka, Stein-Leventhal) syndrome
Gross appearance of polycystic ovaries
Gross appearance of polycystic ovaries
– Both ovaries are 2 to 5 times normal size
– Multiple superficial cysts
– Central homogeneous stroma lacking corpora lutea or albicantia
Histology of the cysts in polycystic ovarian (aka, Stein-Leventhal) syndrome
Histology of the cysts in polycystic ovarian (aka, Stein-Leventhal) syndrome
– Multiple follicular cysts lined by an inner non-luteinized granulosa and an outer hyperplastic theca interna (follicular hyperthecosis)
– Corpora lutea are usually absent
CD10 stains the endometrial stroma
CD10 stains the endometrial stroma
IHC that may be helpful in endometriosis
– Low grade and high grade lesions have differing genetic associations
– Low grade: Most commonly K-ras or _BRAF_ mutations (65% of lesions) with rare TP53 mutations (~8%)
– High grade: Most have TP53 mutations (70%), while K-ras or Braf mutations are rare (~1%)
Molecular pathogenesis of ovarian cancers
Serous carcinoma
What is the most common malignant ovarian neoplasm?
65%
Rate of bilaterality in ovarian serous carcinoma
– Vimentin positive
– CA-125 positive
– More than 60% of high-grade tumors and less than 10% of low-grade tumors positive for p53 over expression
– WT-1 (Wilms tumor-1) positive
IHC in serous carcinoma
– Squamous differentiation is commonly associated with endometrioid carcinoma and rarely with serous carcinoma
– Psammoma bodies are rare in endometrioid carcinomas but are found in serous carcinoma
Some histologic differences between endometrioid carcinoma and serous carcinoma of the ovary
– Most often associated with an appendiceal mucocele
– Extensive mucinous ascites
– Cystic epithelial implants on the peritoneal surfaces
– Intra-abdominal adhesions
Anatomic findings in pseudomyxoma peritonei
– Occurring in postmenopausal women: peak incidence in sixth decade
– Poor prognosis
What is the typical patient associated with carcinosarcoma of the uterus or ovary?
Young women: peak incidence in first and second decades
In which age group does one typically find immature teratomas of the ovary?
Endodermal sinus tumor
Synonym for yolk sac tumor
– Clear cell carcinoma
– Endometrioid carcinoma
Which two histologic subtypes of ovarian epithelial carcinomas are associated with ovarian and pelvic endometriosis?
Transitional (urothelial) cells
Transitional (urothelial) cells
What cell type comprises Brenner tumors?
Usually occur in the seventh decade
In which age group are borderline and transitional cell (Brenner) carcinomas of the ovary seen?
- Atypical urothelial-like cells in poorly defined nests with no stromal invasion (invasion would make carcinoma) -
– Atypical urothelial-like cells in poorly defined nests with no stromal invasion (invasion would make carcinoma)
– “Atypical” = nuclear hyperchromasia, nuclear enlargement, and nuclear pleomorphism
– May have papillary areas lined by multilayer epithelium
– Focal necrosis
Histologic findings that make a Brenner tumor into a borderline transitional cell tumor
Nuclear grooving
Nuclear grooving
What nuclear feature is often seen in Brenner tumors?
- Borderline has no stromal invasion, by definition - Carcinoma has destructive stromal invasion with desmoplasia - May have islands of atypical cells floating in pools of mucin in transitional cell carcinoma
– Borderline has no stromal invasion, by definition
– Carcinoma has destructive stromal invasion with desmoplasia
– May have islands of atypical cells floating in pools of mucin in transitional cell carcinoma
How to distinguish borderline transitional cell tumor of the ovary from transitional cell carcinoma of the ovary?
- Ascites - Hydrothorax (usually right sided) - Ovarian fibroma (can have other solid ovarian tumors, too, but most common is fibroma)
– Ascites
– Hydrothorax (usually right sided)
– Ovarian fibroma (can have other solid ovarian tumors, too, but most common is fibroma)
What are the components of Meigs syndrome?
- Stromal nodule has lower cellularity - Stromal nodule has minimal cytologic atypia and generally less than 10 mitotic figures/10 hpf - Stromal nodule does not have lymphovascular invasion (a prominent feature of low-grade endometrial stromal sarcoma)
– Stromal nodule has lower cellularity
– Stromal nodule has minimal cytologic atypia and generally less than 10 mitotic figures/10 hpf
– Stromal nodule does not have lymphovascular invasion (a prominent feature of low-grade endometrial stromal sarcoma)
Histologic difference between endometrial stromal nodule (benign) and endometrial stromal sarcoma (malignant).
CD10
What immunohistochemical marker stains endometrial stroma and benign endometrial stromal nodule?
Endometrial stromal nodule
Endometrial stromal nodule
A large well-circumscribed mass shows a tan cut surface, scattered cysts and an extensive area of infarction.
Low-grade endometrial stromal sarcoma
Low-grade endometrial stromal sarcoma
Endometrial malignancy associated with extensive plugs of tumor within lymphovascular spaces. This is why the older name for this tumor is “endolymphatic stromal myosis.”
Low-grade endometrial stromal sarcoma
Low-grade endometrial stromal sarcoma
A tan to yellow mass with a slightly irregular margin is associated with tan worm-like plugs of tumor distending vascular spaces.
High-grade stromal sarcoma has: - Marked cytologic atypia - Atypical mitotic figures and necrosis
High-grade stromal sarcoma has:
– Marked cytologic atypia
– Atypical mitotic figures and necrosis
Histologic difference between high-grade (pictured) and low-grade stromal sarcoma.
50% 5-year survival
Clinical behavior of high-grade endometrial stromal arcoma
High-grade stromal sarcoma does not have worm-like vascular plugs
Gross pathological difference between high-grade and low-grade endometrial stromal sarcoma
Myometrial adenomyosis
Myometrial adenomyosis
– Islands of endometrial glands surrounded by endometrial stroma within the myometrium, or endometrial stroma exclusively
– Often the glands appear inactive, and hemosiderin is generally absent
Epithelioid leiomyoma. This should be reported out as a STUMP.
Epithelioid leiomyoma. This should be reported out as a STUMP.
Name the leiomyoma of the myometrium: the tumor is composed of round to polygonal cells. Focally the tumor cells show clear cytoplasm.
Bizarre (symplastic) leiomyoma
Bizarre (symplastic) leiomyoma
Name the leiomyoma of the myometrium: large atypical cells show hyperchromatic nuclei with chromatin smudging.
Leiomyosarcoma
Leiomyosarcoma
Myometrial tumor with interlacing bundles of pleomorphic spindle cells with large nuclei, prominent nucleoli, and mitotic figures
– Mitotic activity is less than 5 mitotic figures/10 hpf
– No coagulative necrosis or cellular pleomorphism
Histologic difference between cellular leiomyoma and leiomyosarcoma.
– Mitotic activity is less than 5 mitotic figures/10 hpf
– No coagulative necrosis or cellular pleomorphism
Histologic difference between bizarre (symplastic) leiomyoma and leiomyosarcoma.
Mitotically active leiomyoma
– Occurs in women younger than 35 years
– Cytologic atypia and necrosis are absent
– Mitotic activity more than 5 mitotic figures/10 hpf, perhaps up to 20 mitotic figures/10 hpf
Mitotic activity generally greater than 5 to 10 mitotic figures/hpf
Mitotic activity in leiomyosarcoma
Negative in leiomyoma because smooth muscle doesn’t stain for CD10, only endometrial stromal cells stain for CD10
CD10 in leiomyomas
Leiomyomas are hormonally responsive; that is, most shrink after menopause
What happens to leiomyomas after menopause?
Mitotically active leiomyoma:
– Women younger than 35
– Smaller than leiomyosarcoma and well circumscribed
– Absence of necrosis, cytologic atypia, and vascular invasion
Some differences between leiomyosarcoma and mitotically active leiomyoma
Adenomatoid tumor
Adenomatoid tumor
Myometrial tumor
features of mesothelial cells, including long and slender microvilli, intracellular lumina, and intracytoplasmic filaments in bundles
EM of adenomatoid tumor of the uterus
Follicular cyst
Follicular cyst
Ovarian cyst. The cyst wall is lined by an inner layer of granulosa cells and an outer layer of theca interna cells.
- Small and round with scanty cytoplasm - Hyperchromatic nuclei with occasional grooves
– Small and round with scanty cytoplasm
– Hyperchromatic nuclei with occasional grooves
What are granulosa cells in a follicular cyst of the ovary?
Larger with abundant cytoplasm and mixed with vessels (b in photomicrograph).
Larger with abundant cytoplasm and mixed with vessels (b in photomicrograph).
What are the theca interna cells of an ovarian follicular cyst?
numerous follicular cysts in both ovaries, anovulation, infertility, hirsutism, oligomenorrhea, and obesity
Polycystic ovarian syndrome (aka, Stein-Leventhal syndrome)
Histopathology of polycystic ovarian syndrome (aka, Stein-Leventhal syndrome)
Histopathology of polycystic ovarian syndrome (aka, Stein-Leventhal syndrome)
– Multiple follicular cysts lined by an inner non-luteinized granulosa and an outer hyperplastic luteinized theca interna (follicular hyperthecosis)
– Corpora lutea are usually absent
Hyperandrogenism with chronic anovulation in women with no other cause
What is the important clinical laboratory finding polycystic ovarian syndrome?
Substantially elevated estrogen production because of the peripheral conversion of androgens to estrogens
In polycystic ovarian (aka, Stein-Leventhal) syndrome, is estrogen production norma, increased, or decreased?
Stromal hyperthecosis
Stromal hyperthecosis
Luteinization of stromal cells not attached to the follicles, arranged singly and in clusters
What do the luteinized stromal cells of stromal hyperthecosis look like?
What do the luteinized stromal cells of stromal hyperthecosis look like?
Luteinized stromal cells are oval or round with eosinophilic or vacuolated cytoplasm and round, plump nuclei
Pregnancy luteoma
Pregnancy luteoma
Solid proliferation of polygonal luteinized cells with abundant eosinophilic granular cytoplasm.
Endometriosis
Defined as the presence of endometrial tissue outside the uterine corpus
Endometriosis
Endometriosis
Pelvic cavity biopsy
CD10 highlights endometrial stroma
IHC in endometriosis
– Papillary serous cystadenoma has an inner lining with small polypoid excrescences and an underlying cystic component
– Serous cystadenomas have a smooth wall to the cyst
Gross differences between a papillary serous cystadenoma and a serous cystadenoma
Benign papillary serous cystadenoma
Benign papillary serous cystadenoma
Single layer of cuboidal cells in a cystic lesion of the ovary
25% to 35%
Rate of bilaterality in serous borderline tumors
Looks just like benign papillary serous cystadenoma of the ovary grossly
Looks just like benign papillary serous cystadenoma of the ovary grossly
What do the gross findings of borderline serous tumor resemble?
Serous borderline tumor
Serous borderline tumor
The tumor is entirely exophytic and shows numerous branching papillary fronds. Note the absence of stromal invasion.
Serous borderline tumor
Serous borderline tumor
Complexity of branching papillae, nuclear stratification and moderate atypia
Serous borderline tumor
Serous borderline tumor
Tumor shows abundant eosinophilic cytoplasm and moderate cytologic atypia. Mitoses are usually uncommon.
Serous borderline tumor
Serous borderline tumor
Hierarchical branching pattern of papillae. The tips of papillae have cell clusters that appear detached. Occasional mitotic figures can be seen.
Weak or negative (pictured) p53 staining essentially excludes high-grade serous carcinoma
Weak or negative (pictured) p53 staining essentially excludes high-grade serous carcinoma
The utility of p53 IHC in distinguishing between borderline serous tumor and serous carcinoma.
Positive staining (pictured) is thought to be associated more with serous carcinoma. Positivity essentially excludes borderline serous tumor.
Positive staining (pictured) is thought to be associated more with serous carcinoma. Positivity essentially excludes borderline serous tumor.
The utility of p53 IHC in distinguishing between borderline serous tumor and serous carcinoma.
Wilms tumor protein
What is the product of the WT-1 gene called?
– This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a subset of patients with Wilms tumor, the gene’s namesake.
– This is why it IHC for this protein is often positive in gynecologic malignancies
What is the function of the Wilms tumor protein (the product of the WT-1 gene)?
Invasive implants (not called metastases because doesn't affect prognosis).
Invasive implants (not called metastases because doesn’t affect prognosis).
Omentectomy in a patient with ovarian borderline serous tumor.
Serous carcinoma (aka, malignant serous tumor) of the ovary
What is the most common malignant ovarian neoplasm?
Peak incidence between 40 and 70 years
What is the most common age of presentation for serous carcinoma (aka, malignant serous tumor) of the ovary?
CA-125
What serum tumor marker is typically elevated in serous carcinoma (aka, malignant serous tumor) of the ovary?
~65% of cases are bilateral
Rate of bilaterality of serous carcinoma (aka, malignant serous tumor) of the ovary.
WT-1 IHC is usually positive for nuclear staining in this group of tumors
WT-1 IHC is usually positive for nuclear staining in this group of tumors
Nuclear stain useful in diagnosing primary urogenital tract neoplasms that shows this pattern of staining
Serous carcinoma (aka, malignant serous tumor) of the ovary
Serous carcinoma (aka, malignant serous tumor) of the ovary
Ovarian tumor.
– Cellular tumor with obvious invasion (desmoplasia).
– Characteristic hyperchromatic nuclei and atypical mitoses
– Vimentin positive
– CA-125 positive
– More than 60% of high-grade tumors and less than 10% of low-grade tumors positive for p53
– WT-1 positive
IHC in serous carcinoma (aka, malignant serous tumor) of the ovary
Up to 75% to 85% of mucinous ovarian tumors are benign
Are the majority of mucinous ovarian tumors benign, borderline, or malignant?
Benign mucinous tumor
What is the most common ovarian epithelial tumor seen in pregnancy?
Bilateral in only 2% to 4% of cases
Rate of bilaterality in benign mucinous tumor of the ovary
Benign mucinous tumor of the ovary
Ovarian cystic neoplasm
Benign mucinous tumor of the ovary
Benign mucinous tumor of the ovary
Cysts, papillary structures, and cryptlike structures are lined by a single layer of columnar cells with clear, apical mucin and small basally located nuclei (picket-fence-like) or intestinal-type epithelium with goblet cells
Mucinous cysts
Mucinous cysts
Which of the two main types of ovarian cysts (mucinous or serous) are more commonly multilocular?
CK7 is usually positive in benign mucinous tumors of the ovary
IHC that is useful in teasing apart colonic mucosa from the epithelial lining of mucinous cystic lesion of the ovary. Why you would ever need to do this is beyond me, but I threw it in anyway, just for giggles.
This ovarian tumor is associated with
– Dermoid cysts in 3% to 5% of cases
– Appendiceal mucoceles
– Pseudomyxoma peritonei
Other conditions that can be associated with benign mucinous tumor of the ovary.
Borderline mucinous tumor has more solid areas
Borderline mucinous tumor has more solid areas
On gross examination, what is one important difference between benign and borderline mucinous tumors of the ovary?
By definition, mucinous borderline tumors (MBT) show greater degree of cell proliferation and nuclear atypia (as seen here) than benign tumors, but without stromal invasion. Borderline and benign areas of this MBT are juxtaposed on the opposing sides of a papillae in this image.
The subdivision of ovarian mucinous tumors into benign, borderline, and malignant is based on the degree of cell proliferation, nuclear atypia, and the presence or absence of stromal invasion. Which one is pictured here?
Mucinous borderline tumor of the ovary. The focus with borderline morphology shows moderate nuclear atypia and occasional mitotic figures.
Mucinous borderline tumor of the ovary. The focus with borderline morphology shows moderate nuclear atypia and occasional mitotic figures.
Ovarian mass
Mucinous borderline tumor, intestinal type, showing columnar cells with abundant eosinophilic cytoplasm, stratified atypical nuclei, and occasional mitotic figures. Intestinal subtype makes up almost 85% of mucinous borderline tumors of the ovary.
Ovarian neoplasm
– This is supposed to be a borderline mucinous neoplasm of the ovary. Good luck figuring that out from this gross picture
– Important to thoroughly sample tumor to exclude areas of invasive malignant tumor
What important thing should the budding pathologist keep in mind when grossing this mucinous tumor of the ovary?
– CEA
– CA 19-9
– Inhibin
– CA 125
What are some serum tumor markers that are elevated in mucinous carcinoma (aka, malignant mucinous tumor) of the ovary?
Mucinous borderline tumor, intestinal type, composed almost entirely of goblet cells. This field shows benign morphology.
Mucinous borderline tumor, intestinal type, composed almost entirely of goblet cells. This field shows benign morphology.
Ovarian tumor
Endocervical-like mucinous borderline tumors (EMBT) account for approximately 15% of mucinous borderline tumors. They are seen in somewhat younger age-group than intestinal type and often associated with endometriosis. They show papillary architecture with atypical cells lining stromal papillae.
Ovarian mass
Endocervical-like mucinous borderline tumor
Endocervical-like mucinous borderline tumor
The atypical cells lining the cyst wall have abundant eosinophilic cytoplasm and form small cellular papillae infiltrated by neutrophils. Neutrophils are also usually present in the luminal mucin.
Mucinous cystadenocarcinoma (aka, malignant mucinous tumor) of the ovary
Mucinous cystadenocarcinoma (aka, malignant mucinous tumor) of the ovary
This ovarian mass had a cyst wall that showed papillae and cribriform glands lined by highly atypical cells with frequent mitoses. The underlying stroma was penetrated by nests of malignant cells with desmoplastic response.
Mucinous cystadenocarcinoma with confluent glands and high-grade nuclear features
Mucinous cystadenocarcinoma with confluent glands and high-grade nuclear features
This ovarian cystic mass had areas of stromal invasion.
WT-1 is positive in serous carcinoma of the ovary but is negative in endometrioid adenocarcinoma
Utility of WT-1 in distinguishing between serous and endometrioid carcinoma of the ovary.
Breast and gastrointestinal tract
Most common primary tissues of origin of Krukenberg tumors
– Vimentin negative
– Cytokeratin 7 and 20 positive
– CEA: positive cytoplasmic staining
IHC in ovarian mucinous cystadenocarcinoma (aka, malignant mucinous tumor)
- Metastatic mucin-secreting adenocarcinoma with signet ring cells originating from an extragenital source - Contains goblet cells in the stroma and is usually bilateral
– Metastatic mucin-secreting adenocarcinoma with signet ring cells originating from an extragenital source
– Contains goblet cells in the stroma and is usually bilateral
Krukenberg tumor
Lungs
Lungs
Most common place of metachronous metastases in ovarian mucinous cystadenocarcinoma (aka, malignant mucinous tumor)
CA 125
Serum tumor marker that is elevated in most cases of endometrioid adenocarcinoma of the ovary.
~30% are bilateral. That is to say, most of these ovarian tumors are unilateral.
What percentage of ovarian endometrioid carcinomas are bilateral?
Endometrioid adenoma of the ovary
Endometrioid adenoma of the ovary
Ovarian mass. The glands resemble normal endometrium. Stroma is moderately cellular. Many of these tumors arise from endometriosis
Endometrioid adenoma of the ovary
Endometrioid adenoma of the ovary
This ovarian mass is lined by cuboidal or columnar epithelium lacking cytologic atypia. Note the resemblance of glands to normal endometrial lining.
Endometrioid borderline tumor
Endometrioid borderline tumor
This ovarian tumor has numerous endometrioid glands scattered in a cellular stroma. Squamous metaplasia is readily evident.
Endometrioid carcinoma
Endometrioid carcinoma
Malignant glands are separated by abundant stroma.
Endometrioid carcinoma, well differentiated (FIGO grade 1)
Endometrioid carcinoma, well differentiated (FIGO grade 1)
The glands are more closely packed in this ovarian mass
Squamous metaplasia is seen in as many as 50% of ovarian endometrioid carcinomas. Such tumors have also been referred to as adenoacanthomas.
Squamous metaplasia is seen in as many as 50% of ovarian endometrioid carcinomas. Such tumors have also been referred to as adenoacanthomas.
Which ovarian malignant neoplasm often has squamous metaplasia?
Squamous metaplasia is seen in as many as 50% of ovarian endometrioid carcinomas. Such tumors have also been referred to as adenoacanthomas.
Squamous metaplasia is seen in as many as 50% of ovarian endometrioid carcinomas. Such tumors have also been referred to as adenoacanthomas.
Which ovarian malignant neoplasm often has squamous metaplasia?
– Endometrioid carcinoma
– Clear cell carcinoma
What are the two most common malignant tumors rising adjacent to or within endometriosis?
Chondrosarcoma
Most common heterologous element seen in carcinosarcoma (aka, MMMT) of the ovary
Clear cell adenofibroma of the ovary
Clear cell adenofibroma of the ovary
This is a rare benign ovarian tumor consisting of glands lined by cuboidal or flattened cells with clear cytoplasm. The glands are separated by fibroblastic stroma.
Clear cell adenofibroma of the ovary
Clear cell adenofibroma of the ovary
Ovarian mass. Dilated glands may create a sponge-like appearance in gross specimens. The lining epithelial cells have abundant clear cytoplasm and lack atypia.
Clear cell adenofibroma of the ovary
Clear cell adenofibroma of the ovary
Ovarian mass. The glands are lined by flattened clear epithelium and separated by fibroblastic stroma.
Borderline clear cell adenofibroma of the ovary
Borderline clear cell adenofibroma of the ovary
Ovarian mass
Clear cell carcinoma of the ovary
Clear cell carcinoma of the ovary
Clear cytoplasm is seen in this ovarian malignancy
Papillary clear cell carcinoma of the ovary
Papillary clear cell carcinoma of the ovary
Ovarian malignancy
Glycogen inclusion
Glycogen inclusion
What makes the clear cells clear in clear cell carcinoma of the ovary?
Clear cell carcinoma of the ovary
Clear cell carcinoma of the ovary
Ovarian malignancy. Low-power view demonstrates a papillary pattern with hobnail-shaped and pleomorphic clear cells.
– Fibroma
-Thecoma
– Granulosa cell tumors
– Sclerosing stromal tumor
– Sertoli cell tumor
– Sertoli-Leydig tumor
– Gynandroblastoma
– Stromal luteoma
– Leydig cell tumor
A list of ovarian sex cord-stromal tumors, just for completeness
Ovarian fibroma
What is the most common sex cord-stromal tumor of the ovary?
Ovarian fibroma
Ovarian fibroma
Name the ovarian mass on the left
- This is an ovarian fibroma - In can be part of Meigs syndrome (ovarian fibroma, ascites, hydrothorax - usually right sided)
– This is an ovarian fibroma
– In can be part of Meigs syndrome (ovarian fibroma, ascites, hydrothorax – usually right sided)
Name the ovarian lesion and its syndromic association.
Greater than 90% of this benign ovary tumors are bilateral at presentation
What percent of ovarian fibromas are bilateral?
Ovarian fibroma
Ovarian fibroma
Ovarian mass. Intersecting bundles of spindle cells, often in a storiform pattern. Diffuse edema is common.
Ovarian fibroma
Ovarian fibroma
Bilateral ovarian mass.
Ovarian fibrothecoma
Ovarian fibrothecoma
Ovarian mass that is in the middle of the spectrum between two other histological patterns
Ovarian fibrothecoma
Ovarian fibrothecoma
Ovarian mass
Ovarian thecoma
Ovarian thecoma
Lobulated, solid, yellow tumor sometimes with cystic change (pictured), hemorrhage and necrosis
– Typical thecoma:sheets and bundles of swollen, lipid-laden, theca-like cells
– Luteinized thecoma: show luteinized stromal cells and luteinized theca-like cells with abundant clear or eosinophilic cytoplasm and central, round nuclei
Two histologic patterns of thecoma
Typical ovarian thecoma
Typical ovarian thecoma
This ovarian tumor is composed predominantly of plump spindle cells with pale cytoplasm. Focally, the tumor cells have vacuolated cytoplasm.
Luteinized ovarian thecoma
Luteinized ovarian thecoma
Luteinized stromal cells and luteinized theca-like cells (with abundant clear or eosinophilic cytoplasm)
Luteinized ovarian thecoma
Luteinized ovarian thecoma
Luteinized stromal cells and luteinized theca-like cells (with abundant clear or eosinophilic cytoplasm)
– Lipid
– The theca are the estrogen (a cholesterol hormone) producing cells in the ovary
What makes the clearing that is seen in theca-like cell cytoplasm in ovarian thecomas?
Middle aged to older women
Age group of adult granulosa cell tumor
Granulosa cell tumors can secrete estrogen, so they can stimulate the endometrium into hyperplasia. In less than 5% of cases, this leads to endometrial carcinoma. So, whenever a patient is diagnosed with adult granulosa cell tumor, she also needs and endometrial biopsy.
What dread complication is occasionally associated with adult granulosa cell tumor.
Adult granulosa cell tumor
Adult granulosa cell tumor
Solid, soft, yellow-tan to gray tumor with cystic areas and hemorrhage
Adult granulosa cell tumor
Adult granulosa cell tumor
Ovarian tumor with “coffee bean” nuclei features:
– Angulated to round
– Often with prominent nuclear folds
Call-Exner bodies
Call-Exner bodies
The distinguishing morphologic feature of microfollicular pattern of adult granulosa cell tumor
Insular pattern of adult granulosa cell tumor
Insular pattern of adult granulosa cell tumor
Which pattern of adult granulosa cell tumor is made up of islands of granulosa cells divided by fibrous trabeculae?
Trabecular pattern of granulosa cell tumor
Trabecular pattern of granulosa cell tumor
Which pattern of granulosa cell tumor comprises cords of neoplastic cells?
Call-Exner bodies
Call-Exner bodies
The distinguishing morphologic feature of microfollicular pattern of adult granulosa cell tumor
Water silk pattern (moire) of adult granulosa cell tumor
Water silk pattern (moire) of adult granulosa cell tumor
Which pattern of adult granulosa cell tumor has cells arranged in undulated rows?
– Vimentin, inhibin, and calretinin positive
– EMA, cytokeratin 7, desmin negative
IHC in adult granulosa cell tumor of the ovary
First three decades of life
Age group most commonly presenting with juvenile granulosa cell tumor of the ovary
Juvenile granulosa cell tumor
Juvenile granulosa cell tumor
most are unilateral, yellow-tan, with cysts, hemorrhage and necrosis
Juvenile granulosa cell tumor
Juvenile granulosa cell tumor
Features solid sheets of cells mixed with small immature follicles of varying sizes and shapes containing secretions
Juvenile granulosa cell tumor
Juvenile granulosa cell tumor
Granulosa cells have round, hyperchromatic, ungrooved nuclei with abundant eosinophilic or clear, vacuolated cytoplasm; luteinization is frequent
Adult granulosa cell tumor has the following features:
– Follicles are more regular in size and shape and contain eosinophilic basement membrane material with degenerating nuclei
– Cells have scanty cytoplasm, and extensive luteinization is absent
– Nuclei are pale, angular to round, and often grooved, with variable mitotic activity
Histologic features that help distinguish between adult and juvenile granulosa cell tumor.
Most tumors are benign; surgical resection usually is curative
Clinical behavior of juvenile granulosa cell tumors
Rare, benign, occurring mostly in first three decades, with a peak incidence in second decade
Most common age of presentation of sclerosing stromal tumors of the ovaries
Sclerosing stromal tumor of the ovary
Sclerosing stromal tumor of the ovary
Ovarian tumor:
– Moderately cellular pseudolobules with numerous thin-walled vessels
– Pseudotubules are composed of fibroblasts and lipid-laden, vacuolated cells separated by edematous connective tissue or dense collagenous stroma
Sclerosing stromal tumor of the ovary
Sclerosing stromal tumor of the ovary
Ovarian tumors with pseudotubules and pseudolobules
Ovarian Sertoli cell tumor
Ovarian Sertoli cell tumor
Ovarian mass. The tumor is composed of closely packed tubules lined by cuboidal to columnar epithelial cells. Notice the lack of nuclear atypia.
IHC for inhibin in a Sertoli-Leydig cell tumor
IHC for inhibin in a Sertoli-Leydig cell tumor
This Sertoli-Leydig cell tumor shows strong cytoplasmic positivity for which IHC marker?
Ovarian Sertoli cell tumor
Ovarian Sertoli cell tumor
Hollow tubules are lined by cuboidal, columnar cells with moderate to abundant pale, occasionally eosinophilic, cytoplasm, and rare to absent nuclear atypia and mitoses
Sertoli-Leydig cell tumor
Androgen-secreting ovarian tumor that may occur at any age; peak incidence in the second decade
Well differentiated Sertoli-Leydig cell tumor
Well differentiated Sertoli-Leydig cell tumor
Ovarian tumor. Hollow or solid tubular pattern with round, oval, elongated, or irregular tubules in a fibrous stroma mixed with clusters of Leydig cells.
Well differentiated Sertoli-Leydig cell tumor
Well differentiated Sertoli-Leydig cell tumor
Ovarian tumor with two cell types, one of which forms tubules, embedded in a fibrous stroma
Intermediate differentiation Sertoli-Leydig cell tumor
Intermediate differentiation Sertoli-Leydig cell tumor
Tubules are less well differentiated that the well differentiated version; more cellular overall; round nuclei with prominent nucleoli
Intermediate differentiation Sertoli-Leydig cell tumor
Intermediate differentiation Sertoli-Leydig cell tumor
Tubules are less well differentiated that the well differentiated version; more cellular overall; round nuclei with prominent nucleoli
Sertoli-Leydig cell tumor
Ovarian mass that can cause erythrocytosis from androgen production
Women of child bearing age
Most common age group affected by ovarian sex cord tumor with annular tubules
One third of cases are associated with Peutz-Jegher syndrome
What syndrome is associated with ovarian sex cord tumor with annular tubules
Ovarian sex cord tumor with annular tubules
Ovarian sex cord tumor with annular tubules
This ovarian tumor is characterized by simple and complex annular tubules encircling hyaline material; simple tubules are shaped like a ring.
Ovarian sex cord tumor with annular tubules
Ovarian sex cord tumor with annular tubules
Ovarian tumor. Epithelial rings are lined by cells that have abundant pale cytoplasm oriented toward the center of the ring and a peripheral nucleus.
Benign, incidental finding at autopsy or surgery when seen in patients with Peutz-Jegher syndrome
Typical clinical presentation of ovarian sex cord tumor with annular tubules
Ovarian stromal luteoma
Ovarian mass. Round nodules of lutein cells that, by definition, are confined within ovarian stroma
Brenner tumor
Brenner tumor
Ovarian mass
Ovarian adult granulosa cell tumor
Ovarian adult granulosa cell tumor
Ovarian mass
Usually benign
Clinical behavior of Leydig cell tumor of the ovary
Ovarian Leydig cell tumor
Ovarian Leydig cell tumor
Ovarian tumor. Sheets, cords, or clusters of polyhedral cells with abundant eosinophilic, finely granular cytoplasm, which may contain small lipid vacuoles. By definition, elongated eosinophilic crystals of Reinke are present in the cytoplasm; however, these may not be obvious
Ovarian Leydig cell tumor
Ovarian Leydig cell tumor
Unilateral, well-circumscribed, solid, usually less than 5 cm in diameter located near the hilum with hemorrhage frequently present
Ovarian dysgenesis
Ovarian dysgerminoma is more common in women with a history of _____.
Peak incidence in second and third decades
Age group most commonly presenting with ovarian dysgerminoma
Ovarian dysgerminoma
Ovarian dysgerminoma
Uniform clusters, nests, and cords of large, round cells with abundant, clear, glycogen-rich cytoplasm, separated by lymphocyte-infiltrated fibrous stroma
Ovarian dysgerminoma
Which ovarian tumor can have non-caseating granulomas and multinucleate syncytiotrophoblastic giant cells?
Gross appearance of ovarian dysgerminoma
Gross appearance of ovarian dysgerminoma
Ovarian tumor. External surface is smooth and gray-white; cut surface is lobulated, gray-white, with hemorrhage or necrotic areas giving it a yellow, pink, or tan color.
– Placental alkaline phosphatase (PLAP) and vimentin positive
– Cytokeratin is usually negative and EMA is negative
IHC in ovarian dysgerminoma
Endodermal sinus tumor
Another name for malignant yolk sac tumor of the ovary
Ovarian yolk sac tumor
Ovarian yolk sac tumor
Ovarian tumor. Reticular pattern of small cystic spaces lined by cells with clear cytoplasm containing glycogen or lipid.
Schiller-Duval bodies
Schiller-Duval bodies
Characteristic finding of in yolk sac tumor (endodermal sinus tumor): glomeruloid, epithelial-lined space containing a polypoid projection covered by cuboidal to columnar cells with a single central vessel
Hepatoid type
Subtype of yolk sac tumor that mimics hepatocellular carcinoma
Embryonal carcinoma of the ovary
Embryonal carcinoma of the ovary
Ovarian neoplasm. Solid, papillary, or glandular pattern with sheets and nests of malignant large ovoid or polygonal cells forming syncytiotrophoblastic giant cells in a fibrotic stroma.
Ovarian choriocarcinoma
Ovarian choriocarcinoma
Ovarian neoplasm with both cytotrophoblasts and syncytiotrophoblasts.
Elevated serum ?-HCG
Tumor marker associated with ovarian choriocarcinoma
Ovarian choriocarcinoma
Usually a part of a mixed germ cell tumor
immature teratoma of the ovary
immature teratoma of the ovary
Small round blue and immature neural cells with rosettes associated with neuropil and mucinous glands.
Children
Age group that present with pure immature teratoma of the ovary
Almost always found in phenotypic women with an underlying gonadal disorder, like pure gonadal dysgenesis or complete androgen insensitivity syndrome
Patient population that develops gonadoblastoma
Ovarian gonadoblastoma
Ovarian gonadoblastoma
Ovarian mass in a woman with gonadal dysgenesis. The image shows clusters with admixture of germ cells and sex-cord type cells separated by abundant fibrous stroma and calcified areas.
Ovarian gonadoblastoma
Ovarian gonadoblastoma
The germ cells in _____ are similar to those seen in dysgerminoma ? with abundant clear cytoplasm. Note the calcification to the right.
Ovarian gonadoblastoma
Ovarian gonadoblastoma
Ovarian tumor in a woman with gonadal dysgenesis that shows abundant hyalinized basement membrane material in and around the cell nests.
Pure gonadoblastoma is a benign tumor; however, it’s clinical course may be complicated by the development of a malignancy (usually Dysgerminoma) in the germ cell component.
Clinical course of gonadoblastoma.
Ovarian hypercalcemic small cell carcinoma
Ovarian hypercalcemic small cell carcinoma
Ovarian mass in a young woman presenting with symptoms of hypercalcemia.
– Generally noncontributory
– Undifferentiated tumor negative for neuroendocrine markers, inhibin, and CEA
IHC in hypercalcemic small cell carcinoma of the ovary
Ovarian masses are metastatic tumors in less than 10% of cases
What percentage of ovarian masses represent metastatic disease?
Krukenberg tumor
Krukenberg tumor
Ovarian mass
Chlamydia species or Neisseria gonorrhoeae followed by polymicrobial infection
Most common causes of acute and chronic salpingitis
Salpingitis isthmica nodosa
Salpingitis isthmica nodosa
– Out pouchings of tubal epithelium in the thickened muscle wall of the fallopian tube
– Small nests or cysts with tubal epithelium lining spaces surrounded by a muscle coat
Salpingitis isthmica nodosa
Glands have been shown to connect to tubal lumen
_____ is analogous to adenomyosis in the uterus.
Gross picture of a complete mole
Gross picture of a complete mole
Complete mole
Most common form of gestational trophoblastic disease.
Serum HCG continues to rise after 14 weeks of gestation, when the HCG normally drops.
What serum marker is indicative of complete (hydatidiform) mole?
Complete mole
Complete mole
– All villi are abnormal; most are enlarged and rounded with cystic swelling
– Central cisternae, or empty spaces without vessels in the center of the villi, are readily identified
-Irregular diffuse circumferential proliferation of trophoblasts instead of normal, even, perivillous distribution
– Absence of fetal parts, including nucleated red blood cells
Hydatidiform mole. Can demonstrate cytologic atypia of the hypertrophic syncytiotrophoblasts.
Hydatidiform mole. Can demonstrate cytologic atypia of the hypertrophic syncytiotrophoblasts.
Evacuation and curettage from a uterus that was disproportionate large for gestational age
About 2% of complete molar pregnancies
What percentage of complete molar gestations are followed by choriocarcinoma?
Partial mole
Partial mole
– Edematous villi with irregular, scalloped borders admixed with normal-appearing villi
– Trophoblast proliferation is focal, as opposed to circumferential in CM
– Fetal vessels often contain nucleated red blood cells
Exaggerated placental site
Exaggerated placental site
Endometrial biopsy from patient that had abnormal uterine bleeding after successfully delivering a normal baby. Invasion of myometrium by cytologically unremarkable intermediate trophoblasts.
Most are triploid due to two sperm fertilizing one ovum
Pathogenesis of partial mole
Placental Site Trophoblastic Tumor
Placental Site Trophoblastic Tumor
Endometrial biopsy after delivery of normal pregnancy. Predominance of intermediate trophoblasts that split the myometrial fibers.
Most follow normal pregnancy or missed abortion. Not associated with molar pregnancy.
Clinical context of placental site trophoblast tumor
– Medium-sized cells with single nucleus, opaque cytoplasm, and no vacuoles
– Cells may be atypical and mitotically active with irregular cell borders
What do intermediate trophoblasts look like?
– Most are benign
– 10% to 15% are malignant
Clinical behavior of placental site trophoblastic tumor
Treated with hysterectomy
What is the therapy for placental site trophoblastic tumor?
Endometrial hyperplasia because the golden-yellow color of this fibrothecoma indicates that it is potentially a hormone producing tumor.
Endometrial hyperplasia because the golden-yellow color of this fibrothecoma indicates that it is potentially a hormone producing tumor.
A 54-year-old patient underwent resection of this ovarian mass. What concurrent clinical condition is likely?
Coagulative necrosis
Coagulative necrosis
The single feature that is the most worrisome for leiomyosarcoma
From the surface of the epithelium to the deepest portion of the tumor
How is the Breslow depth of melanoma measured?
From the the adjacent basement membrane of the closest dermal papilla.
How is the thickness of squamous cell carcinoma evaluated?
– Most common: squamous cell carcinoma
– Second most common: malignant melanoma (8%-10% of vulvar cancers)
What are the two most common vulvar cancers?
- Vulvar Paget disease - CK7+, CK20?, CEA+, GCDFP-15+ (aka, BRST-2+), HMB-45?, uroplakin III?
– Vulvar Paget disease
– CK7+, CK20?, CEA+, GCDFP-15+ (aka, BRST-2+), HMB-45?, uroplakin III?
Diagnosis and IHC profile of this vulvar lesion.
Cervical tunnel cluster
Cervical tunnel cluster
Benign cervical process that shows tightly packed glands with mucin production.
In contrast to minimal deviation adenocarcinoma (aka, adenoma malignum), cervical tunnel clusters show a striking lobular configuration and the glands are uniform without complex architecture, appreciable cytologic atypia, or mitotic activity.
How to distinguish cervical tunnel clusters from minimal deviation adenocarcinoma (aka, adenoma malignum) of the uterine cervix.
Carcinoembryonic antigen (CEA)
Carcinoembryonic antigen (CEA)
A marker of colonic mucosa that is also a marker of mucinous epithelium in ovarian tumors.
Never. Immature teratomas always arise de novo.
How often do immature teratomas arise out of mature teratomas?
Squamous cell carcinoma
What is the most common malignancy that arises from mature cystic teratomas?
Gonadoblastoma
Gonadoblastoma
Gonadoblastoma
Gonadoblastoma
– Nests of primordial germ cells intimately admixed with sex cord elements that resemble immature Sertoli and granulosa cells.
– The granulosa-like cells surround spaces filled with eosinophilic basement material.
Dysgerminoma
What malignancy can grow out ovarian gonadoblastoma
S-100 positive
IHC in granular cell tumors of the vulva (or any other body part, for that matter)
Stromal invasion or lack thereof
What is the most useful histologic characteristic in distinguishing borderline (benign) papillary lesion of the ovary from malignant serous lesion of the ovary?
Intrauterine device This is actinomyces
Intrauterine device
This is actinomyces
This patient most likely has a history of _____.
Papillary serous cystadenofibroma
Papillary serous cystadenofibroma
Ovarian neoplasm
Arias Stella reaction
Arias Stella reaction
– Hypersecretory endometrium
– Complex glands with frequent intraluminal epithelial infoldings and increased secretions
– Cells can have a hobnail appearance
Sexual abuse
Vulvar intraepithelial neoplasia in a child should cause one to entertain suspicions of _____.
Differentiated vulvar intraepithelial neoplasia
Which type of vulvar intraepithelial neoplasia is associated with the following:
– Unrelated to HPV
– Older patients
– It is felt to be of greater risk for progression to invasion than the more common basaloid or warty HPV-related VIN lesions
The transformation zone of the cervix
Most squamous intraepithelial lesions of the cervix arise from:
3 mm
Maximum thickness that an invasive squamous cell carcinoma of the cervix can have and still be considered “microinvasive carcinoma.”
Serous carcinoma of the uterus
Which type of uterine carcinoma is not related to unopposed estrogen?
has histologically benign glands in a malignant stroma
Müllerian adenosarcoma of the uterus:
– Follicle cyst
– Corpus luteum cyst
– Hyperractio luteinalis
– Luteoma of pregnancy
A list of non-neoplastic causes of ovarian masses
Benign cystic teratoma
What is the most common germ cell tumor of the ovary?
Complete moles
Do partial moles or complete moles have more pronounced trophoblast proliferation?
Differentiated VIN is likely to show nuclear staining with p53, while squamous cell hyperplasia should not.
Utility of IHC in distinguishing between differentiated VIN and squamous cell hyperplasia.
– p57KIP paternally imprinted
– Will be present in partial mole (since it includes maternal genes)
– Will be absent in complete mole (since it has only paternal genetic material)
IHC used in distinguishing between complete and partial mole.
p16
Increased staining for _____ supports HPV-related dysplasia.
Endocervical polyp with reactive cells
Endocervical polyp with reactive cells
Cervical biopsy
Perhaps the most common are stage III or IV adenocarcinomas of the ovary and fallopian tube, which make their way to the cervix and vagina via the endometrial cavity.
Most common primary tumor that metastasizes to the cervix and vagina.
Serous carcinoma of the fallopian tube
Most common primary gynecologic tumor in patients with a BRCA1 or BRCA2 mutation.
Sixth to seventh decades
Peak age of serous carcinoma of the ovary
More than 80%
Proportion of patients with serous carcinoma that have an elevated CA-125
Gross description of serous carcinomas
Gross description of serous carcinomas
Solid and cystic tumors that frequently show areas of necrosis and hemorrhage
Serous carcinoma
Serous carcinoma
Ovarian mass. High grade lesions are characterized by complex, branching papillae and glands forming narrow, slit-like spaces with destructive stromal invasion. Can have solid growth.
– Positive: CK7, WT-1, Ber-EP4, and CD15
– Negative: CK20
Ovarian serous carcinoma IHC
CK7 positive; CK20 negative
CK7 and CK20 profile in ovarian serous carcinoma
Endometrioid carcinomas are rarely positive for WT1 in contrast to serous carcinomas
Immunohistochemistry in distinguishing between endometrioid carcinoma and serous carcinoma of the female reproductive tract.
Serous carcinoma
Which common gynecologic malignancy is positive on WT1 on ICH?
Endometrium
If serous carcinoma involves both the ovaries and the endometrium, what is the most likely primary source?
SKT11
Which gene is frequently mutated in minimal deviation mucinous adenocarcinoma (aka, adenoma malignum) of the cervix? Hint: it is the same gene that is mutated in Peutz-Jeghers syndrome.
Minimal deviation mucinous adenocarcinoma of the cervix
Minimal deviation mucinous adenocarcinoma of the cervix
Most, and rarely all, of the tumor is composed of tall mucinous epithelium which closely resembles normal endocervical columnar epithelium but lack the *characteristic cytologic features of malignancy*.
Serous neoplasm of low malignant potential
Serous neoplasm of low malignant potential
Alternative name for serous borderline tumor of the ovary
Serous borderline tumor
Gross finding of an ovarian cystic neoplasm shows “cauliflower-like” papillary projections.
Serous borderline tumor lack destructive stromal invasion
Main histologic difference between serous borderline tumor and serous carcinoma of the ovary
Positive in Ewing sarcoma and granulosa cell tumor
Tumors most commonly associated with CD99 staining
– Endometrial stromal sarcoma is CD10 positive (negative for other 2)
– Leiomyosarcoma is caldesmon and desmon positive and CD10 variable
IHC panel that can help in distinguishing endometrial stromal sarcoma from leiomyosarcoma
t(7;17) resulting in the fusion gene JAZF1-JJAZ1
What is the most common recurring cytogenetic aberration in endometrial stromal sarcomas?
Site-dependent expression of WT-1 in serous carcinoma of the female reproductive tract
Nuclear WT-1 immunoexpression is found in high-grade serous carcinoma of the ovary, tubes, and peritoneum; however, uterine serous carcinoma generally lacks WT-1.
Endometrioid adenocarcinoma of the ovary
Ovarian malignancy that is positive for CK 7, EMA, ER, and PR; negative for inhibin and calretinin.
– Colorectal carcinoma: generally has dirty necrosis and is CK20 positive
– Ovarian endometrioid carcinoma: not much necrosis and is CK7 positive
There may be significant histologic overlap between primary ovarian endometrioid carcinoma and colorectal carcinoma metastatic to the ovary. How can the two be differentiated?
Patients with Sertoli-Leydig cell tumors are on the average 25 years younger
Patients with Sertoli-Leydig cell tumors are on the average 25 years younger
Sertoli-Leydig cell tumor (pictured) and ovarian endometrioid adenocarcinoma can have overlapping histologic features. What hint in the clinical information can help distinguish the two?
Immunoprofile of endometrial clear cell carcinoma
Immunoprofile of endometrial clear cell carcinoma
Positive for cytokeratin 7, Cam 5.2, 34?E12, carcinoembryonic antigen, Leu-M1 (aka, CD15), vimentin, Bcl-2, p53, and CA-125. CK20 and PRs are negative, whereas expression of ER and Her2/neu is variable.
Endometrial clear cell carcinoma; doesn't have to have clear cells only
Endometrial clear cell carcinoma; doesn’t have to have clear cells only
Large polygonal cells with abundant cytoplasm and large, atypical nuclei.
Tubulocystic pattern
Tubulocystic pattern
Which pattern of endometrial clear cell carcinoma is represented in the photomicrograph?
Endometrial clear cell carcinoma
Endometrial clear cell carcinoma
The diagnosis of _____ in the gynecologic tract is based more on the presence of the classic architectural patterns of this entity than the presence of clear cells.
Difference in the molecular pathology of endometrial endometrioid carcinoma and endometrial serous carcinoma.
Microsatellite instability and mutations in the PTEN, ?-catenin, and K-ras genes have been widely associated with EEC,40,41 whereas p53 mutations have been identified in most endometrial serous carcinomas.
Undifferentiated carcinoma of the uterus
Undifferentiated carcinoma of the uterus
Malignancy of the lower uterine segment forming sheets of monomorphic cells, often with abundant necrosis.
FIGO 3 endometrioid carcinoma is composed of nests of cohesive cells in contrast with undifferentiated carcinoma, which characteristically displays a dyshesive or less cohesive growth pattern.
FIGO 3 endometrioid carcinoma is composed of nests of cohesive cells in contrast with undifferentiated carcinoma, which characteristically displays a dyshesive or less cohesive growth pattern.
Important histologic difference between FIGO grade 3 endometrioid endometrial adenocarcinoma and undifferentiated endometrial carcinoma (pictured).
Undifferentiated endometrial carcinoma
Undifferentiated endometrial carcinoma
The presence of myxoid features with rhabdoid cells in an endometrial neoplasm that otherwise comprises sheets of monomorphic malignant cells.
Undifferentiated endometrial carcinoma
Which endometrial malignancy is most associated with DNA mismatch repair gene mutations (like hMLH1), ie, Lynch syndrome?
Undifferentiated carcinoma of the endometrium
What uterine malignancy is associated with hypermethylation of the hMLH1 gene promoter?
Peritheliomatous growth pattern
Peritheliomatous growth pattern
When necrosis is extensive, the viable tumor cells may condense around blood vessels. This pattern is called _____.
Mitotically active leiomyoma (mitotic count has no bearing on prognosis)
Mitotically active leiomyoma (mitotic count has no bearing on prognosis)
Uterine smooth muscle tumor with a mitotic index of up to 20/10 hpf.
Leiomyoma with atypia (aka, symplastic leiomyoma)
Leiomyoma with atypia (aka, symplastic leiomyoma)
Leiomyomas with atypia (ancient change like in schwannoma), without other worrisome features (ie, necrosis or increased mitotic rate).
Coagulative necrosis
Coagulative necrosis
This kind of necrosis in uterine smooth muscle tumors is characterized by ghost outlines of necrotic cells and an abrupt (not sclerotic) transition from viable to necrotic (as is seen in hyalinized infarct necrosis). This kind of necrosis portends a worse outcome.
p16
What is cyclin-dependent kinase inhibitor 2a also known as?
Endometrial stromal tumor
Endometrial stromal tumor
Endometrial stromal neoplasm in which the tumor cells have uniform round hyperchromatic nuclei and scanty cytoplasm.
Normal endometrial stromal cells with no staining of the endometrial epithelial cells. As such, endometrial stromal tumors are usually positive for CD10.
Normal endometrial stromal cells with no staining of the endometrial epithelial cells. As such, endometrial stromal tumors are usually positive for CD10.
What does CD10 stain in the endometrial samples?
There is diffuse strong staining of tumor cell nuclei for WT-1 in all parts of endometrial stomal tumor.
There is diffuse strong staining of tumor cell nuclei for WT-1 in all parts of endometrial stomal tumor.
WT-1 staining in endometrial stromal tumor.
Endometrial stromal sarcoma
Endometrial stromal sarcoma
Stromal neoplastic cells invade underlying normal myometrium.
Endometrial stromal nodule (*not* endometrial stromal sarcoma)
Endometrial stromal nodule (*not* endometrial stromal sarcoma)
Endometrial stromal proliferation with smooth, pushing, *non-infiltrative* borders.
t(7;17)(p15q21) that results in a JAZF1/JJAZ1 gene fusion
Most common cytogenetic abnormality in endometrial stromal tumors and endometrial stromal sarcomas.
Thecoma
Thecoma
Ovarian neoplasm composed of sheets or nodular aggregates of plump to spindle cells with paler vacuolated cytoplasm. The plump cells resemble the cecum interna cells of the developing follicles.
Positive for vimentin, inhibin, calretinin, and CD10, but negative for cytokeratin and EMA.
Immunohistochemical features of ovarian thecoma.
Oil red O shows the lipid vacuole
What histochemical stain can help with the diagnosis of thecoma?
Stromal luteoma, Leydig cell tumor, and steroid cell tumor, not otherwise specified.
What are the 3 steroid cell tumors of the ovary, which are comprised of hormone-producing cells?
Positive for inhibin and calretinin; rare focal positivity for pancytokeratin.
Immunophenotype of stromal luteomas.
Leydig cell tumor
Leydig cell tumor
Ovarian steroid cell tumor that is characterized by the presence of Reinke crystals.
Hilus cell tumor (less common type) and non-hilar tumor (very rare), based on location and presents cell of origin.
What are the 2 general classifications of Leydig cell tumors?
Leydig cell tumor
Leydig cell tumor
Fibrinoid replacement of the blood vessel walls is associated with which to steroid tumor of the ovary?
Leydig cell tumors
Leydig cell tumors
Reinke crystals are present in the cytoplasm of which steroid cell tumor of the ovary?
Leydig cell tumors
Leydig cell tumors
Reinke crystals are present in the cytoplasm of which steroid cell tumor of the ovary?
The diagnosis of a hilus cell (Leydig cell) tumor can be favored, even if crystal-free, if it is juxtaposed to the hilar nerve fibers of the ovary.
Even though Reinke crystals are required for a definitive diagnosis of a hilus cell tumor, a diagnosis can still be made without crystals the following criteria is met.
Hexagonal
General shape of Reinke crystals on ultrastructural cross section.
By the presence of Reinke crystals.
How can Leydig cell tumors be distinguished from stromal luteomas?
Steroid tumors that do not have diagnostic features of either stromal luteoma or Leydig cell tumor.
Steroid cell tumor, not otherwise specified, comprises 50% of all steroid cell tumors. What are they?
The vast majority present with the virilization (androgenic manifestations).
What is the most common manifestation of a steroid cell tumor, not otherwise specified?
Positive for CK 7 and negative for inhibin and CK 20
Positive for CK 7 and negative for inhibin and CK 20
What is the immunophenotype of ovarian clear cell carcinoma?
Solid, tubular cystic, tubulopapillary, and papillary. The papillary morphology is pictured.
Solid, tubular cystic, tubulopapillary, and papillary. The papillary morphology is pictured.
What are the 4 different histomorphologic we’ll growth patterns seen in clear cell carcinoma of the ovary?
Glycogen (which is PAS positive and diastase sensitive).
What substance in the cytoplasm of clear cell carcinomas of the ovary makes the cells clear?
Leydig cell tumors are much more frequently located in the hilar region of the ovary, with smaller size the has Reinke crystals. Leydig cell tumors also occur in older age steroid cell tumors, NOS.
What are the main histologic weighs to distinguish between Leydig cell tumors of the ovary and steroid cell tumors, NOS.
Sertoli cell tumors
Sertoli cell tumors
Which ovarian neoplasm is typically composed of well formed although or solid tubules lined by columnar to cuboidal cells with moderate to abundant eosinophilic or vacuolated cytoplasm and round to oval regular nuclei with nuclear grooves?
Beta-catenin
Nuclear over-expression of _____ has recently been demonstrated in 40% to 60% of low-grade endometrial stromal sarcomas, but not in uterine smooth muscle tumors.
Yellow with solid and cystic areas
Yellow with solid and cystic areas
What is the cut surface appearance, grossly, of granuloa cell tumor of the ovary?
Calretinin and inhibin
Which combination of immunohistochemical markers is considered sensitive markers for adult granulosa cell tumor?
Reticulin staining demonstrating distinct fibers surrounding large groups of cells helps to distinguish adult granulosa cell tumor from cellular fibroma and from thecoma.
What is the difference in reticulin staining in adult granulosa cell tumor versus fibroma and thecoma?
Yes
Is a following immunohistochemical pattern compatible with an adult granulosa cell tumor? Positive for pancytokeratin, negative for epithelial membrane antigen, positive for calretinin, positive for WT-1?
Clinical stage
What is the most important prognostic factor in adult granulosa cell tumor?
Embryonal carcinoma
Generally strongly and diffusely positive for cytokeratin, PLAP, CD30, and OCT4. Usually negative for EMA.
D2-40 and CD117
Which markers, typically not thought of as ovarian markers, are positive in dysgerminoma (as well as seminoma of the testicle)?
While PLAP and OCT3/4 are positive in both, CD30 is positive only in embryonal carcinoma.
How can PLAP, OCT3/4, and CD30 be used to distinguish between embryonal carcinoma and dysgerminoma?

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