Ovary

5.1 ATYPICAL PROLIFERATIVE/BORDERLINE SEROUS TUMOR (APST/SBT) VS. NONINVASIVE LOW-GRADE SEROUS CARCINOMA (LGSC)/NONINVASIVE MICROPAPILLARY SEROUS CARCINOMA

	Atypical Proliferative/Borderline Serous Tumor	Noninvasive Low-Grade Serous Carcinoma/Noninvasive Micropapillary Serous Carcinoma
Age	Mean 49 years	Mean 54 years
Location	Within ovary with or without exophytic surface component; may be confined to surface	Within ovary with or without exophytic surface component; may be confined to ovarian surface
Symptoms	Commonly asymptomatic; may have nonspecific pelvic pain or urinary symptoms	Commonly asymptomatic; may have nonspecific pelvic pain, increasing abdominal girth, bloating, early satiety
Signs	Pelvic/adnexal mass	Pelvic/adnexal mass
Etiology	Unknown; originates from serous-type inclusions, possibly originating from tubal epithelial implantation; KRAS and BRAF mutations	Evolves in a slow, stepwise manner from APST and is related to BRAF/KRAS mutations
Gross and histology	1. Intracystic and exophytic components	1. Intracystic and exophytic components
	2. Hierarchical branching, tufting, and apparent detachment of cell clusters; some micropapillae may be present but not as numerous as in noninvasive LGSC; no invasion (Figs. 5.1.1 5.1.2, 5.1.3, 5.1.4)	2. Nonhierarchical branching with abundant micropapillae (at least five times as long as they are wide); Medusa appearance (Figs. 5.1.6 and 5.1.7); papillary fusion with cribriform pattern (Figs. 5.1.8 and 5.1.9); APST component usually present (quantitative criteria for distinction from APST: pure noninvasive LGSC areas without intervening foci of APST must measure at least 5 mm in greatest extent); no invasion
	3. Tubal-type epithelium, often ciliated, focally with hobnail or dense eosinophilic cytoplasm (Fig. 5.1.5); mild cytologic atypia; may have psammoma bodies; extracellular mucin may be present	3. Tubal-type epithelium, may be ciliated; mild to occasionally moderate cytologic atypia with small prominent nucleoli (Figs. 5.1.9 and 5.1.10); psammoma bodies common; extracellular mucin may be present (Fig. 5.1.10)
	4. 12% have noninvasive peritoneal implants; 1% have invasive implants; those with exophytic component more often with implants (see Chapter 6)	4. Peritoneal implants usually present and majority are invasive (see Chapter 6)
Special studies	Not useful in this differential	Not useful in this differential
Treatment	Salpingo-oophorectomy with staging	TAH-BSO, comprehensive staging +/- debulking; chemotherapy not effective
Prognosis	Benign if confined to ovaries (i.e., without associated peritoneal implants); noninvasive implants confer risk of invasive low-grade serous carcinoma of approximately 16%	Survival >95% if confined to ovaries; if invasive peritoneal implants (i.e., peritoneal involvement with LGSC) present, stages II and III are indolent with 5-/10-year survival approximately 75%/45%, respectively

Figure 5.1.1 Atypical proliferative (borderline) serous tumor with hierarchical branching pattern, tufting, and detachment of cell clusters.

Figure 5.1.2 Atypical proliferative (borderline) serous tumor with hierarchical branching, detachment of cell clusters, and apparent detachment of larger papillary processes.

Figure 5.1.3 Intracystic atypical proliferative (borderline) serous tumor with cyst wall at right lined by single layer of benign-appearing serous epithelium.

Figure 5.1.4 Atypical proliferative (borderline) serous tumor showing ciliated epithelium and apparent detachment of individual cells and cell clusters.

Figure 5.1.5 Atypical proliferative (borderline) serous tumor with detachment of atypical cell clusters.

Figure 5.1.6 Low-power magnification of noninvasive low-grade serous carcinoma (serous borderline tumor with micropapillary features) displaying diffuse micropapillary architecture with “Medusa head” configuration.

Figure 5.1.7 Noninvasive low-grade serous carcinoma (serous borderline tumor with micropapillary features) with large papilla containing elongated micropapillary projections (“Medusa head” appearance). Same case as in Figure 5.1.6, higher magnification.

Figure 5.1.8 Cribriform pattern of noninvasive low-grade serous carcinoma (serous borderline tumor with micropapillary and cribriform features).

Figure 5.1.9 Cribriform and solid noninvasive low-grade serous carcinoma displaying mild nuclear atypia with small prominent nucleoli. Same case as in Figure 5.1.8, higher magnification.

Figure 5.1.10 Cribriform pattern of noninvasive low-grade serous carcinoma. Extracellular mucin is noted.

5.2 ATYPICAL PROLIFERATIVE/BORDERLINE SEROMUCINOUS TUMOR (APSMT) VS. LOW-GRADE SEROMUCINOUS CARCINOMA

	Atypical Proliferative/Borderline Seromucinous Tumor	Low-Grade Seromucinous Carcinoma
Age	Mean 38-40 years	Mean 47 years
Location	Intracystic within ovarian stroma	Within ovarian stroma
Symptoms	Commonly asymptomatic; may have pelvic or abdominal pain or other endometriosis-associated symptoms	Very limited data suggest pelvic pain or other endometriosis-associated symptoms
Signs	Pelvic/adnexal mass	Pelvic/adnexal mass
Etiology	Endometriosis; limited data suggest KRAS and ARID1A mutations present	Likely arise through progression of APSMT, which is derived from endometriosis
Gross and histology	1. Usually unilocular and associated with endometriosis; about one-third bilateral; mean 8 cm	1. Usually confined to ovaries; 16% bilateral; mean 10.5 cm; solid or mixed solid/cystic
	2. Hierarchical branching pattern; invasion absent (Figs. 5.2.1 5.2.2, 5.2.3)	2. Complex papillary, glandular, microglandular and solid patterns (Figs. 5.2.6 5.2.7, 5.2.8); occasional stromal hyalinization; invasion is based on confluent growth; occasional destructive invasion (Fig. 5.2.9); APSMT component usually present
	3. Endocervical-like mucinous epithelium admixed with serous and other cell types (including indifferent-type cells); neutrophils and extracellular mucin usually present; mild atypia, rare mitotic figures (Figs. 5.2.3 5.2.4, 5.2.5)	3. Endocervical-like mucinous cells and eosinophilic indifferent cells; may also contain hobnail, squamous, clear, endometrioid-like, and focal signet ring-like cells; neutrophils and extracellular mucin usually present; mild to focally moderate cytologic atypia with low mitotic activity (Figs. 5.2.9 and 5.2.10)
	4. Rarely associated with peritoneal implants	4. Rarely associated with peritoneal metastases
Special studies	Not useful in this differential	Not useful in this differential
Treatment	USO and staging	Insufficient data to justify difference from other low-grade ovarian carcinomas
Prognosis	Generally benign behavior; cases with implants may be at increased risk for recurrence/progression	Limited data suggest very good prognosis given predominance of stage I

Figure 5.2.1 Atypical proliferative (borderline) seromucinous tumor with hierarchical papillary branching.

Figure 5.2.2 Atypical proliferative (borderline) seromucinous tumor with marked neutrophilic infiltration and edema.

Figure 5.2.3 Atypical proliferative (borderline) seromucinous tumor with pseudostratified epithelium with tufting and occasional neutrophils.

Figure 5.2.4 Atypical proliferative (borderline) seromucinous tumor with papillae lined by single layer of mildly atypical indifferent-type and tubal-type cells with small nucleoli. Some cells display cilia.

Figure 5.2.5 Atypical proliferative (borderline) seromucinous tumor with pseudostratified epithelium with some ciliated cells, mild atypia, prominent neutrophilic infiltrate, and both intracellular and extracellular mucin.

Figure 5.2.6 Low-grade seromucinous carcinoma with confluent papillary pattern.

Figure 5.2.7 Low-grade seromucinous carcinoma with confluent glandular pattern.

Figure 5.2.8 Low-grade seromucinous carcinoma with confluence of glands with cribriforming, in many areas lacking fibrovascular support.

Figure 5.2.9 Low-grade seromucinous carcinoma displaying marked gland crowding, infiltrative pattern of stromal invasion, abundant neutrophils, and extracellular mucin.

Figure 5.2.10 Low-grade seromucinous carcinoma with pseudostratification of mucinous epithelium and mild to focally moderate nuclear atypia. Note presence of neutrophils (upper right).

5.3 AUTOIMPLANTS OF ATYPICAL PROLIFERATIVE/BORDERLINE SEROUS TUMOR (APST/SBT) VS. ATYPICAL PROLIFERATIVE/BORDERLINE SEROUS TUMOR WITH MICROINVASION/MICROINVASIVE CARCINOMA

	Autoimplants of Atypical Proliferative/Borderline Serous Tumor	Atypical Proliferative/Borderline Serous Tumor with Microinvasion/Microinvasive Carcinoma
Age	Mean 36 years	Mean 42 years
Location	Exophytic portion of primary ovarian tumor, often between papillae; rarely in intracystic component	Primary ovarian tumor
Symptoms	Commonly asymptomatic; may have nonspecific pelvic pain or urinary symptoms	Commonly asymptomatic; may have nonspecific pelvic pain or urinary symptoms
Signs	Pelvic or adnexal mass	Pelvic or adnexal mass
Etiology	Unknown; possibly arise from detachment of exophytic papillae from APST, perhaps due to infarction, and subsequent reattachment	Unknown; possibly, APST epithelium may undergo mutation (i.e., BRAF), infarction, terminal differentiation, or senescence Size criteria vary for distinction of microinvasion from invasive low-grade serous carcinoma (LGSC): 5 mm is most commonly used upper limit for microinvasion
Gross and histology	1. Two-thirds are multifocal; range in size up to 2.5 cm; 93% have been associated with and resemble desmoplastic peritoneal implants (see Chapter 6); 10% have invasive LGSC (invasive implants) involving the peritoneum Lesional cells present on ovarian surface or within fibrous tissue between large papillae (Fig. 5.3.1) Fibroblastic stroma, often with chronic inflammation, overshadows the epithelial component with which it merges (Figs. 5.3.2 5.3.3, 5.3.4, 5.3.5) and has circumscribed border with underlying tissue. Fibrinous inflammatory exudate often present	1. No gross correlates of microinvasion; stroma of APST may be dense and hyalinized or edematous; rarely cellular and fibroblastic when inflammation or infarction present Lesional cells located within stroma of tumor
	2. Single cells, cell clusters, small, smoothly contoured glands and papillae with mild or moderate atypia without invasive features (Figs. 5.3.2 5.3.3, 5.3.4, 5.3.5); 37% associated with infarcted papillae	2. Eosinophilic type (Figs. 5.3.6 and 5.3.7): epithelial cells with central, bland nuclei and abundant eosinophilic cytoplasm bud into the stromal cores of the papillae singly and in small clusters, occasionally forming glands, often surrounded by a space, which may be lined by flattened cells
	3. 20% of serous borderline tumors with autoimplants have micropapillary features (noninvasive LGSC)	3. Micropapillary type (Figs. 5.3.8 and 5.3.9): solid nests and micropapillae usually surrounded by a space display an infiltrative pattern (“small focus of low-grade carcinoma” or “microinvasive carcinoma” terminology may be used); larger papillae occasionally present and are referred to as “macropapillary” (Figs. 5.3.10 and 5.3.11) In both eosinophilic and micropapillary types, the cytologic features are similar to the noninvasive epithelium lining the papillae
Special studies	Autoimplants presumed to have similar immunoprofile as desmoplastic implants; remainder of tumor same as APST	Microinvasive cells often lose ER, PR, and WT1 expression; Ki 67 proliferation index low; noninvasive eosinophilic cells show similar pattern; otherwise same as APST
Treatment	Same as APST	Same as APST
Prognosis	Limited data; same as APST stratified by implant type	Same as APST when stratified by stage and implant type

Figure 5.3.1 Autoimplant on surface of ovary.

Figure 5.3.2 Autoimplant with a few glands overshadowed by an inflamed fibroblastic stroma resembling a desmoplastic implant (see Chapter 6). Note fibrosis and calcification at upper left.

Figure 5.3.3 Autoimplant. Higher magnification of Figure 5.3.2 showing a few glands embedded in fibroblastic stroma with focal hemorrhage and fibrinous exudate at right.

Figure 5.3.4 Autoimplant with fibroblastic inflamed stroma containing small glands and papillae at upper right.

Figure 5.3.5 Autoimplant. Higher magnification of Figure 5.3.2 showing inflamed fibroblastic stroma covered by fibrinous exudate, with both psammomatous and nonpsammomatous calcifications at left.

Figure 5.3.6 Eosinophilic type of microinvasion displaying glands lined by eosinophilic cells with a hobnail pattern, and single epithelial cells, most of which are surrounded by a space. The nuclei of these eosinophilic cells resemble those of some cells in the overlying noninvasive epithelium.

Figure 5.3.7 Eosinophilic type of microinvasion displaying a single ovoid epithelial cell with eosinophilic cytoplasm in the stroma, surrounded by a space.

Figure 5.3.8 Microinvasive carcinoma displaying micropapillae surrounded by spaces and psammomatous calcification. Note that the qualitative appearance is similar to frankly invasive low-grade serous carcinoma.

Figure 5.3.9 Microinvasive carcinoma displaying micropapillae surrounded by spaces and psammomatous calcification.

Figure 5.3.10 Macropapillary pattern of microinvasive carcinoma (see Section 5.5). Eosinophilic-type microinvasive cells are also present.

Figure 5.3.11 Microinvasive carcinoma and eosinophilic type of microinvasion. Eosinophilic cells (center), micropapillae (left), and a macropapilla (right). Higher magnification of Figure 5.3.10.

5.4 LYMPH NODE “INVOLVEMENT” BY ATYPICAL PROLIFERATIVE/BORDERLINE SEROUS TUMOR (APST/SBT) VS. LYMPH NODE WITH ENDOSALPINGIOSIS

	Lymph Node “Involvement” by Atypical Proliferative/Borderline Serous Tumor	Lymph Node with Endosalpingiosis
Age	Mean 40 years	Wide age range of adults
Location	Nodal sinuses including subcapsular sinus; pelvic and para-aortic groups; rarely seen in other lymph node groups	Intracapsular and within fibrous trabeculae; pelvic and para-aortic groups
Symptoms	No symptoms referable to the nodes	Asymptomatic
Signs	None	None
Etiology	Lymphatic filtration of peritoneal fluid containing exfoliated cells from ovarian tumor surface; alternative possibilities include origin from nodal endosalpingiosis	Associated with salpingitis, APST, and low-grade serous carcinoma; endosalpingiosis is more common in women with low-grade serous tumors compared to women without tumors
Gross and histology	1. Eosinophilic cells resembling those seen in microinvasion, singly and in clusters and small papillae, in sinuses and, in florid cases, in parenchyma (Figs. 5.4.1 and 5.4.2)	1. Simple glands lined by flattened cuboidal to columnar ciliated tubal-type epithelium, usually within node capsule (Figs. 5.4.6 and 5.4.7)
	2. Endosalpingiosis usually present, often closely associated with the eosinophilic cells; endosalpingiotic glands may display intraglandular tufting with detachment of cell clusters (Figs. 5.4.3 5.4.4, 5.4.5)	2. Occasionally with minimal and blunt papillae; isolated eosinophilic cells not present
Special studies	Nodal cells often lose ER, PR, and WT1 expression and have decreased Ki 67 proliferation index in comparison to similar cells in primary APST; other markers same as APST	ER+, PR+, WT1+, PAX8+, CK7+, calretinin-
Treatment	Same as APST	None
Prognosis	Same as APST after correction for implant type	Benign

Figure 5.4.1 Lymph node involvement by atypical proliferative (borderline) serous tumor showing detached papillary clusters.

Figure 5.4.2 Lymph node involvement by ovarian atypical proliferative (borderline) serous tumor showing detached small clusters and individual cells with abundant eosinophilic cytoplasm.

Figure 5.4.3 Lymph node involvement by atypical proliferative (borderline) serous tumor (APST). The lymph node capsule and nodal parenchyma contain endosalpingiotic-type glands showing prominent tufting and cell clusters within glands. Alternatively, this could also represent APST arising within nodal endosalpingiosis.

Figure 5.4.4 Lymph node involvement by atypical proliferative (borderline) serous tumor. The epithelial stratification, including detached cell clusters, exceeds that of endosalpingiosis.

Figure 5.4.5 Lymph node involvement by atypical proliferative (borderline) serous tumor (APST). The nodal parenchyma contains endosalpingiotic-type glands showing prominent tufting and cell clusters within glands, as well as clusters of epithelial cells outside of glands. Alternatively, this could also represent APST arising within nodal endosalpingiosis.

Figure 5.4.6 Endosalpingiosis characterized by two benign glands within the lymph node capsule.

Figure 5.4.7 Higher magnification of Figure 5.4.6 displays benign tubal-type epithelium lacking atypia or mitotic figures.

5.5 MACROPAPILLARY PATTERN OF INVASIVE LOW-GRADE SEROUS CARCINOMA (LGSC) VS. SEROUS ADENOFIBROMA/CYSTADENOFIBROMA

	Macropapillary Pattern of Invasive Low-Grade Serous Carcinoma	Serous Adenofibroma/Cystadenofibroma
Age	Mean 50 years	Mean 61 years; wide age range of adults
Location	Within ovary	Within ovary
Symptoms	Commonly asymptomatic; may have nonspecific pelvic pain, increasing abdominal girth, bloating, and early satiety	Commonly asymptomatic; may have pelvic pain or discomfort
Signs	Pelvic/adnexal mass	Pelvic/adnexal mass
Etiology	Limited data suggest KRAS or BRAF mutations present in macropapillary component	May arise from surface epithelial inclusions and surrounding stroma; epithelium is polyclonal and nonneoplastic in most cases; copy number aberrations (often gain of chromosome 12) may be found in stromal fibroblasts in the majority of cases
Gross and histology	1. Mean size 12 cm; often bilateral; otherwise grossly same as micropapillary LGSC	1. One-third of benign ovarian serous tumors are adenofibromas/cystadenofibromas (remainder are unilocular or multilocular serous cystadenomas without significant fibromatous components); usually solid, often with cystic component
	2. Invasive papillae characteristic of LGSC with papillary structures ≥0.3 cm in diameter, surrounded by a space, usually involving >50% of the tumor (Figs. 5.5.1 5.5.2, 5.5.3, 5.5.4); often seen in combination with usual micropapillary LGSC (Fig. 5.5.5)	2. Broad fibrous papillary processes may be exophytic or endophytic within cysts; rarely, endophytic appearance in noncystic fibrous areas resembles macropapillary pattern of LGSC (Figs. 5.5.6 5.5.7, 5.5.8)
	3. Epithelium bland, cuboidal to columnar, mild atypia, often ciliated, similar to LGSC (Figs. 5.5.3 and 5.5.4); atypical proliferative (borderline) serous tumor component usually present	3. Papillae are lined by benign tubal-type epithelium lacking atypia (Figs. 5.5.8 and 5.5.9); focal small papillary proliferations with minimal stroma may be present
Special studies	Not useful in this differential	Not useful in this differential
Treatment	Same as LGSC	USO or cystectomy
Prognosis	Limited data; likely same as LGSC	Benign

Figure 5.5.1 Invasive low-grade serous carcinoma, macropapillary pattern, displays an infiltrative pattern of papillae of varying sizes, some >3 mm in diameter.

Figure 5.5.2 Invasive low-grade serous carcinoma, macropapillary pattern (same case as Fig. 5.5.1), displays prominent spaces surrounding the papillae.

Figure 5.5.3 Invasive low-grade serous carcinoma, macropapillary pattern, displays minimal atypia and cilia in the serous epithelium lining the papillae.

Figure 5.5.4 Invasive low-grade serous carcinoma, macropapillary pattern, with large papillae lined by serous epithelium with minimal atypia and focal areas with ciliated cells.

Figure 5.5.5 Invasive low-grade serous carcinoma with macropapillae and micropapillae.

Figure 5.5.6 Serous cystadenofibroma with intracystic papillae at top left, and endophytic papillae within the fibrous stroma toward bottom right.

Figure 5.5.7 Serous cystadenofibroma, higher magnification of Figure 5.5.6, showing endophytic papilla.

Figure 5.5.8 Serous cystadenofibroma with papillae in small cyst, lined by benign serous epithelium.

Figure 5.5.9 Serous cystadenofibroma, higher magnification of Figure 5.5.8, with papillae lined by benign serous epithelium.

5.6 HIGH-GRADE SEROUS CARCINOMA VS. LOW-GRADE SEROUS CARCINOMA

	High-Grade Serous Carcinoma	Low-Grade Serous Carcinoma
Age	Mean 60-63 years	Mean 47-57 years
Location	Ovarian surface and within stroma	Ovarian surface and within stroma
Symptoms	Pelvic pain, increasing abdominal girth, bloating, early satiety, urinary symptoms	Pelvic pain, increasing abdominal girth, bloating, early satiety, urinary symptoms
Signs	Pelvic/abdominal mass, ascites	Pelvic/abdominal mass, ascites
Etiology	Majority derive from serous tubal intraepithelial carcinoma (STIC), usually of fimbrial origin; nearly all have TP53 mutations; a substantial proportion have either germline or somatic BRCA1 or BRCA2 mutation or epigenetic silencing of a BRCA gene	Derive from progression of atypical proliferative (borderline) serous tumor (APST) through noninvasive low-grade serous carcinoma; KRAS and BRAF mutations
Gross and histology	1. Ovaries normal sized or slightly enlarged in one-third to one-half of cases with subcentimeter surface nodules; remaining show enlarged solid and/or cystic ovaries, 8-10 cm; fallopian tube fimbriae may be prominent and tumorous and may be splayed across ovarian surface; usually bilateral adnexal involvement and nearly always with peritoneal carcinomatosis or extensive bowel invasion; bilateral adnexa may be obliterated by tumor	1. Intracystic and exophytic components; peritoneal involvement or carcinomatosis usually present
	2. Papillary, glandular, slit-like, and solid patterns, commonly intermixed (Figs. 5.6.1 5.6.2, 5.6.3); less commonly thick urothelial-like papillae (see Section 5.30)	2. Haphazard infiltrative pattern of nests and micropapillae, often surrounded by a space (Figs. 5.6.6 5.6.7, 5.6.8)
	3. Large epithelial cells with marked atypia, often with bizarre nuclear forms (Figs. 5.6.3 5.6.4, 5.6.5); large prominent nucleoli, abundant mitotic activity with abnormal forms; psammoma bodies are usually present but may sometimes be seen only focally	3. Serous (tubal)-type epithelium, occasionally ciliated; mild to occasionally moderate cytologic atypia with small prominent nucleoli (Figs. 5.6.8 5.6.9, 5.6.10); psammoma bodies common (Figs. 5.6.6, 5.6.7, and 5.6.9); mitotic figures are absent or infrequent
	4. STIC is the only morphologically noninvasive component	4. Noninvasive component with nonhierarchical branching, Medusa appearance, papillary fusion (see Section 5.1); APST component often present; ciliated cells more commonly seen in APST component
Special studies	Aberrant p53 expression; p16+ (extensive, often diffuse); Ki 67 index high	p53 wild-type staining pattern; no diffuse p16 expression; Ki 67 index low (mildly elevated)
Treatment	Staging (with debulking when indicated); chemotherapy (in neoaduvant or adjuvant setting)	TAH-BSO, comprehensive staging +/- debulking; chemotherapy not effective
Prognosis	Stage III patients have 5-year survival of 45%-50% if optimally debulked; suboptimal debulking has 20%-30% 5-year survival	Indolent with 5-/10-year survival approximately 75%-80%/45%, respectively, for stage III

Figure 5.6.1 High-grade serous carcinoma displays interanastomosing slit-like spaces and high-grade nuclear atypia.

Figure 5.6.2 High-grade serous carcinoma, same case as Figure 5.6.1, with glands and slit-like spaces lined by markedly atypical epithelium.

Figure 5.6.3 Solid pattern of high-grade serous carcinoma with relatively uniform but high-grade nuclei with large prominent nucleoli and chromatin clumping.

Figure 5.6.4 High-grade serous carcinoma with glands and clustered cells with bizarre nuclear features; focal necrosis and inflamed fibrotic stroma are noted.

Figure 5.6.5 High-grade serous carcinoma (HGSC) with isolated and clustered large cells with abundant eosinophilic cytoplasm and marked nuclear atypia. Isolated cells in the stroma, as seen here, are more commonly seen in treated HGSCs and rare in chemotherapy-naive tumors.

Figure 5.6.6 Low-grade serous carcinoma showing infiltrative pattern of small papillae and numerous psammoma bodies.

Figure 5.6.7 Low-grade serous carcinoma, same case as Figure 5.6.6, composed of micropapillae lined by a single layer of bland cuboidal to columnar epithelium.

Figure 5.6.8 Low-grade serous carcinoma with invasive micropapillae displaying uniform and round nuclei, evenly dispersed chromatin, and small nucleoli. Mitotic figures are not seen.

Figure 5.6.9 Low-grade serous carcinoma with psammomatous calcification within the cores of several papillae; note mild atypia with small prominent nucleoli.

Figure 5.6.10 Low-grade serous carcinoma (same case as Fig. 5.6.8) with small and medium-sized papillae and focal glandular differentiation. Note low-grade atypia and uniform nuclei.

5.7 HIGH-GRADE SEROUS CARCINOMA (HGSC) WITH ATYPICAL PROLIFERATIVE (BORDERLINE) SEROUS TUMOR-LIKE PATTERN VS. ATYPICAL PROLIFERATIVE/BORDERLINE SEROUS TUMOR (APST)

	High-Grade Serous Carcinoma with Atypical Proliferative (Borderline) Serous Tumor-Like Pattern	Atypical Proliferative/Borderline Serous Tumor
Age	Postmenopausal	Mean 49 years
Location	Within ovaries	Within ovary with or without exophytic surface component; may be confined to surface
Symptoms	Pelvic pain, increasing abdominal girth, bloating, early satiety, urinary symptoms	Commonly asymptomatic; may have nonspecific pelvic pain or urinary symptoms
Signs	Pelvic/abdominal mass, ascites	Pelvic/adnexal mass
Etiology	TP53 missense mutation in one case reported; however, TP53 mutations are expected	Unknown; originates from serous-type inclusions, possibly originating from tubal epithelial implantation; KRAS and BRAF mutations
Gross and histology	1. Bilateral, intracystic tumors	1. Intracystic and exophytic components
	2. Hierarchical papillary branching resembling APST architecture (Figs. 5.7.1 5.7.2, 5.7.3, 5.7.4)	2. Hierarchical branching, tufting, and apparent detachment of cell clusters; no invasion (Figs. 5.7.7 5.7.8, 5.7.9, 5.7.10)
	3. Typical high-grade cytology of serous carcinoma (Figs. 5.7.5 and 5.7.6) with high mitotic index	3. Tubal-type epithelium, ciliated, focally with hobnail or dense eosinophilic cytoplasm; mild cytologic atypia (Figs. 5.7.9 and 5.7.10); may have psammoma bodies; low mitotic index
	4. This high-grade “noninvasive” pattern is occasionally seen focally in otherwise typical HGSC but is pure in <0.5% of HGSC	4. 12% have noninvasive peritoneal implants; those with exophytic component more often with implants
Special studies	Aberrant p53 staining pattern; p16+ (extensive, often diffuse); Ki 67 index high	p53 wild-type staining pattern; no diffuse p16 expression; Ki 67 index low
Treatment	Staging (with debulking when indicated), chemotherapy (in adjuvant or neoadjuvant setting)	Salpingo-oophorectomy with staging
Prognosis	Patient described was alive and well after 6 years; expected outcome should be similar to classic high-grade serous carcinoma	Benign if confined to ovaries (i.e., without associated peritoneal implants); noninvasive implants confer risk of invasive low-grade serous carcinoma of approximately 16%

Figure 5.7.1 High-grade serous carcinoma with atypical proliferative (borderline) serous tumor-like pattern characterized by hierarchical branching without obvious stromal invasion.

Figure 5.7.2 High-grade serous carcinoma with atypical proliferative (borderline) serous tumor-like pattern with hierarchical branching, tufting, and detachment of cell clusters. There is no obvious stromal invasion.

Figure 5.7.3 High-grade serous carcinoma with atypical proliferative (borderline) serous tumor-like pattern, same case as Figure 5.7.1, showing epithelial proliferation, detachment of cell clusters, focal bridging of surface papillae, and no invasion of the stromal cores of the papillae.

Figure 5.7.4 High-grade serous carcinoma with atypical proliferative (borderline) serous tumor-like pattern, same case as Figure 5.7.2. Epithelial proliferation with stratification and detachment of cell clusters.

Figure 5.7.5 High-grade serous carcinoma with atypical proliferative (borderline) serous tumor-like pattern, same case as Figure 5.7.2. The cytologic features of high-grade serous carcinoma are more evident at high magnification; nuclear enlargement, hyperchromasia, prominent nucleoli, and a few mitotic figures are seen.

Figure 5.7.6 High-grade serous carcinoma with atypical proliferative (borderline) serous tumor-like pattern (same case as Figs. 5.7.1 and 5.7.3); high-grade cytologic features with epithelial stratification, nuclear enlargement, hyperchromasia, and occasional mitotic figures.

Figure 5.7.7 Atypical proliferative (borderline) serous tumor with hierarchical branching pattern. Stromal invasion is absent.

Figure 5.7.8 Atypical proliferative (borderline) serous tumor with epithelial stratification, tufting, and focal detachment of cell clusters.

Figure 5.7.9 Atypical proliferative (borderline) serous tumor displaying epithelial tufting, a hobnail-like pattern, and mild cytologic atypia. Cilia are present.

Figure 5.7.10 Atypical proliferative (borderline) serous tumor displaying mild cytologic atypia, prominent eosinophilic cytoplasm, and detached individual cells and cell clusters. Mitotic figures are not seen.

5.8 HIGH-GRADE SEROUS CARCINOMA VS. CARCINOSARCOMA (MALIGNANT MULLERIAN MIXED TUMOR; MMMT)

	High-Grade Serous Carcinoma	Carcinosarcoma (Malignant Mullerian Mixed Tumor; MMMT)
Age	Mean 60-63 years	Mean 65-66 years
Location	Ovarian surface and within stroma	Ovarian surface and within stroma
Symptoms	Pelvic pain, increasing abdominal girth, bloating, early satiety, urinary symptoms	Pelvic pain, increasing abdominal girth, bloating, early satiety, urinary symptoms
Signs	Pelvic/abdominal mass, ascites	Pelvic/abdominal mass, ascites
Etiology	Majority derive from serous tubal intraepithelial carcinoma, usually of fimbrial origin; nearly all have TP53 mutations; a substantial proportion have either germline or somatic BRCA1 or BRCA2 mutation or epigenetic silencing	Majority derive from serous tubal intraepithelial carcinoma, usually of fimbrial origin; nearly all have TP53 mutations
Gross and histology	1. Ovaries normal sized or slightly enlarged in one-third to one-half of cases with subcentimeter surface nodules; remaining show enlarged solid and/or cystic ovaries, 8-10 cm; fallopian tube fimbriae may be prominent and tumorous and may be splayed across ovarian surface; usually bilateral adnexal involvement and nearly always with peritoneal carcinomatosis or extensive bowel invasion	1. Ovaries normal sized or slightly enlarged in one-third to one-half of cases with subcentimeter surface nodules; remaining show enlarged solid and/or cystic ovaries, 8-10 cm; fallopian tube fimbriae may be prominent and tumorous and may be splayed across ovarian surface; usually bilateral adnexal involvement and nearly always with peritoneal carcinomatosis or extensive bowel invasion
	2. Papillary, glandular, slit-like, and solid patterns, commonly intermixed (Figs. 5.8.1 5.8.2, 5.8.3, 5.8.4, 5.8.5); less commonly thick urothelial-like papillae (see Section 5.30)	2. Epithelial component usually displays high-grade serous patterns with papillary, glandular, and solid patterns, commonly intermixed (Figs. 5.8.6 5.8.7, 5.8.8); endometrioid patterns may be present
	3. Large epithelial cells with marked atypia, often with bizarre nuclear forms (Figs. 5.8.3 5.8.4, 5.8.5); large prominent nucleoli and abundant mitotic activity with abnormal forms	3. Large epithelial cells with marked atypia, often with bizarre nuclear forms; large prominent nucleoli and abundant mitotic activity with abnormal forms
	4. Sarcomatous component absent; carcinomatous component may on occasion have spindle cell features (see Section 5.17)	4. Sarcomatous component with high-grade spindle cell differentiation with high mitotic activity and marked cytologic atypia; myxoid or small cell areas may be present; heterologous elements commonly present (>50%), most often cytologically malignant cartilage, rhabdomyoblasts, occasionally osteoid, and liposarcoma (Fig. 5.8.9)
Special studies	Aberrant p53 expression, CK7+, p16+ (diffuse), WT1+, CAM5.2+, BER-EP4+, PAX8+	Epithelial component: aberrant p53 expression, CK7+, p16+ (diffuse), WT1+, CAM5.2+, BER-EP4+; sarcomatous component generally has similar profile but may stain more weakly or focally for epithelial markers; PAX8 often negative in sarcomatous component
Treatment	Staging (with debulking when indicated), chemotherapy (in neoadjuvant or adjuvant setting)	Staging (with debulking when indicated), chemotherapy (in neoadjuvant or adjuvant setting)
Prognosis	Stage III patients have 5-year survival of 45%-50% if optimally debulked; suboptimal debulking has 20%-30% 5-year survival	Stage III patients have 5-year survival of 20%-25%

Figure 5.8.1 High-grade serous carcinoma with poorly differentiated solid and glandular patterns with slit-like spaces.

Figure 5.8.2 High-grade serous carcinoma with poorly differentiated glandular pattern. Note slit-like spaces (arrow).

Figure 5.8.3 High-grade serous carcinoma with glands lined by high-grade epithelium infiltrating a spindle cell stroma lacking significant atypia in the spindle cells.

Figure 5.8.4 High-grade serous carcinoma with high-grade nuclear atypia.

Figure 5.8.5 High-grade serous carcinoma with marked nuclear atypia, glands, and slit-like spaces.

Figure 5.8.6 Carcinosarcoma with broad papillae composed of highly cellular spindle cell stroma; the papillae are lined by high-grade malignant epithelial cells.

Figure 5.8.7 Carcinosarcoma, same case as Figure 5.8.6, with marked atypia of spindle cell stroma with markedly enlarged hyperchromatic nuclei.

Figure 5.8.8 Carcinosarcoma with malignant stroma containing tumor giant cells with bizarre hyperchromatic nuclei, and high-grade malignant glands resembling high-grade serous carcinoma.

Figure 5.8.9 Carcinosarcoma with heterologous chondrosarcomatous and liposarcomatous components.

5.9 HIGH-GRADE SEROUS CARCINOMA VS. HIGH-GRADE ENDOMETRIOID CARCINOMA

	High-Grade Serous Carcinoma	High-Grade Endometrioid Carcinoma
Age	Mean 60-63 years	Mean 55-58 years
Location	Ovarian surface and within stroma	Within ovary
Symptoms	Pelvic pain, increasing abdominal girth, bloating, early satiety, urinary symptoms	Pelvic pain, increasing abdominal girth, bloating, early satiety, vaginal bleeding, urinary symptoms
Signs	Pelvic/abdominal mass, ascites	Pelvic/abdominal mass, ascites
Etiology	Majority derive from serous tubal intraepithelial carcinoma (STIC), usually of fimbrial origin; nearly all have TP53 mutations; a substantial proportion have either germline or somatic BRCA1 or BRCA2 mutation or epigenetic silencing	Endometriosis; germline hMLH1 or hMSH2 mutation (Lynch syndrome) in a small subset; PTEN, β-catenin (CTNNB1), KRAS, ARID1A, and PIK3CA mutations; a subset of cases may have TP53 mutations
Gross and histology	1. Ovaries normal sized or slightly enlarged in one-third to one-half of cases with subcentimeter surface nodules; remaining show enlarged solid and/or cystic ovaries, 8-10 cm; fallopian tube fimbriae may be prominent and tumorous and may be splayed across ovarian surface; usually bilateral adnexal involvement and nearly always with peritoneal carcinomatosis or extensive bowel invasion	1. Usually unilateral, stage I in almost half; mean size 15 cm; cystic or cystic and solid; cysts contain dark brown viscous fluid (old blood +/- mucus); papillary or nodular growths arise from cyst lining
	2. Papillary, glandular, slit-like, and solid patterns, commonly intermixed (Figs. 5.9.1 5.9.2, 5.9.3, 5.9.4, 5.9.5); less commonly thick urothelial-like papillae	2. Poorly differentiated areas may have solid growth with infiltrative pattern of glands, cribriform growth, nests, and solid masses with jagged edges (Figs. 5.9.6 5.9.7, 5.9.8); architecturally well-differentiated areas with confluent glandular epithelial proliferation and/or cribriform growth resembling endometrial endometrioid carcinoma are often present (Fig. 5.9.7)
	3. Large epithelial cells with marked atypia, often with bizarre nuclear forms (Figs. 5.9.4 and 5.9.5); large prominent nucleoli, abundant mitotic activity with abnormal forms	3. Columnar epithelium with sharp luminal gland margins in architecturally well-differentiated areas (Fig. 5.9.9); may display variable range of nuclear atypia/mitotic activity, including enlarged, round to ovoid nuclei with hyperchromasia, prominent nucleoli, and high mitotic index in both glandular and solid areas
	4. STIC is the only noninvasive component present	4. Squamous differentiation in half (Fig. 5.9.10); adenofibromatous component often present; associated endometriosis is present in majority and often shows atypia, hyperplasia, and other features reflecting origin within endometriotic cyst or associated atypical proliferative (borderline) endometrioid tumor; sex cord-like differentiation may be present (Fig. 5.9.8)
Special studies	• Aberrant p53 expression; p16+ (extensive, often diffuse), WT1+	• p53 may show aberrant staining pattern in a subset; no diffuse p16 expression; WT1 usually (-)
	• No loss of staining for DNA mismatch repair proteins (MLH1, PMS2, MSH2, and/or MSH6)	• Loss of staining for DNA mismatch repair proteins (MLH1, PMS2, MSH2, and/or MSH6) in a subset
Treatment	Staging (with debulking when indicated), chemotherapy (in adjuvant or neoadjuvant setting)	Staging (with debulking when indicated), chemotherapy (in adjuvant or neoadjuvant setting) except for low-grade stage IA/B; hormonal suppression may be used for recurrence
Prognosis	Stage III patients have 5-year survival of 45%-50% if optimally debulked; suboptimal debulking has 20%-30% 5-year survival	Stage I >90% survival; stage-stratified analyses show somewhat better prognosis compared to high-grade serous carcinoma in advanced stage

Figure 5.9.1 High-grade serous carcinoma with solid, papillary, and glandular patterns.

Figure 5.9.2 High-grade serous carcinoma with intraglandular papillary pattern with necrosis.

Figure 5.9.3 High-grade serous carcinoma with high-grade nuclear atypia (higher magnification of Fig. 5.9.2). The gland at the left resembles an endometrioid-type gland but displays the same high-grade atypia seen in the papillary areas.

Figure 5.9.4 High-grade serous carcinoma infiltrating a desmoplastic stroma with bizarre nuclear features and necrosis.

Figure 5.9.5 High-grade serous carcinoma. Higher magnification of Figure 5.9.4 with marked nuclear atypia and large prominent nucleoli.

Figure 5.9.6 High-grade endometrioid carcinoma showing solid pattern.

Figure 5.9.7 Cribriform pattern of high-grade endometrioid carcinoma.

Figure 5.9.8 High-grade endometrioid carcinoma with sex cord-like pattern (see Section 5.16).

Figure 5.9.9 High-grade endometrioid carcinoma. Note the cuboidal to columnar cells with flat luminal edges. The degree of atypia is not as severe as in high-grade serous carcinoma.

Figure 5.9.10 High-grade endometrioid carcinoma with squamous differentiation. This area of the tumor is better differentiated than in other areas.

5.10 ATYPICAL PROLIFERATIVE (BORDERLINE) MUCINOUS TUMOR (APMT) VS. APMT WITH INTRAEPITHELIAL CARCINOMA

	Atypical Proliferative (Borderline) Mucinous Tumor (APMT)	APMT with Intraepithelial Carcinoma
Age	Mean 50 years	Mean 50 years
Location	Within ovary	Within ovary
Symptoms	Pelvic/abdominal pain and increasing abdominal girth	Pelvic/abdominal pain and increasing abdominal girth
Signs	Large pelvic/abdominal mass	Large pelvic/abdominal mass
Etiology	Arise in mucinous cystadenomas; KRAS mutations; rarely BRAF mutations	Arise in mucinous cystadenomas; KRAS mutations; rarely BRAF mutations
Gross and histology	1. Nearly always unilateral, mean size 22 cm; grossly similar to mucinous cystadenomas, with large, mucin-filled cysts; papillary growths sometimes arise in cyst walls	1. Nearly always unilateral, mean size 22 cm; grossly similar to mucinous cystadenomas, with large, mucin-filled cysts; papillary growths sometimes arise in cyst walls
	2. Architectural complexity with glandular crowding and cystic areas with epithelial stratification, intraglandular papillary growth, and detached epithelial clusters (Figs. 5.10.1 and 5.10.2); mucinous epithelial lining displays abundant basophilic or eosinophilic cytoplasm with grade 1-2 atypia; areas of cystadenoma with small basal nuclei may be present; proliferative areas with atypical architecture and cytology constitute >10% of the tumor, displaying nuclear enlargement, mild hyperchromasia, prominent nucleoli, and pseudostratification, often with mitotic figures (Figs. 5.10.2 and 5.10.3)	2. Architectural complexity with glandular crowding and cystic areas with epithelial stratification, intraglandular papillary growth, and detached epithelial clusters (Figs. 5.10.4 and 5.10.5); mucinous epithelial lining displays abundant basophilic or eosinophilic cytoplasm; areas of cystadenoma with small basal nuclei; areas of grade 3 atypia are present, displaying unequivocal cytologic features of malignancy with nuclear enlargement, hyperchromasia, prominent nucleoli, pseudostratification, and often with mitotic figures (Figs. 5.10.5 and 5.10.6)
	3. Tumors should be well sampled to exclude invasion	3. Tumors should be well sampled to exclude invasion
Special studies	Of no use for this differential diagnosis	Of no use for this differential diagnosis
Treatment	USO	USO
Prognosis	Benign	Rare cases recur or metastasize; virtually 100% survival if well sampled (two blocks/centimeter maximum diameter) and metastatic carcinoma to the ovary is rigorously excluded

Figure 5.10.1 Atypical proliferative (borderline) mucinous tumor with cystic architecture and epithelial stratification/intraglandular papillary growth.

Figure 5.10.2 Atypical proliferative (borderline) mucinous tumor with mild nuclear pseudostratification and cytologic atypia with small prominent nucleoli.

Figure 5.10.3 Atypical proliferative (borderline) mucinous tumor. The nuclear features are insufficient for intraepithelial carcinoma.

Figure 5.10.4 Atypical proliferative (borderline) mucinous tumor with intraepithelial carcinoma. The architecture is similar to atypical proliferative (borderline) mucinous tumor without intraepithelial carcinoma.

Figure 5.10.5 Atypical proliferative (borderline) mucinous tumor with intraepithelial carcinoma. The epithelium is stratified with cells showing high-grade atypia, enlarged and prominent nucleoli, and occasional mitotic figures. Note the loss of mucin compared with Figure 5.10.3.

Figure 5.10.6 Atypical proliferative (borderline) mucinous tumor with intraepithelial carcinoma. The cells show round and large vesicular nuclei with prominent nucleoli.

5.11 ATYPICAL PROLIFERATIVE (BORDERLINE) MUCINOUS TUMOR (APMT) WITH MICROINVASION VS. APMT WITH GLAND RUPTURE

	Atypical Proliferative (Borderline) Mucinous Tumor (APMT) with Microinvasion	APMT with Gland Rupture
Age	Mean 50 years	Mean 50 years
Location	Within ovary	Within ovary
Symptoms	Pelvic/abdominal pain, increasing abdominal girth	Pelvic/abdominal pain, increasing abdominal girth
Signs	Large pelvic/abdominal mass	Large pelvic/abdominal mass
Etiology	APMT arises in mucinous cystadenomas; KRAS mutations; rarely BRAF mutations; pathogenesis of microinvasion unclear	APMT arises in mucinous cystadenomas; KRAS mutations; rarely BRAF mutations; gland rupture may be due to infarction or possibly due to intraoperative manipulation
Gross and histology	1. Nearly always unilateral, mean size 22 cm; grossly similar to mucinous cystadenomas, with large, mucin-filled cysts; papillary growths sometimes arise in cyst walls	1. Nearly always unilateral, mean size 22 cm; grossly similar to mucinous cystadenomas, with large, mucin-filled cysts; papillary growths sometimes arise in cyst walls
	2. Architectural complexity with glandular crowding and cystic areas with epithelial stratification, intraglandular papillary growth, and detached epithelial clusters; mucinous epithelial lining displays abundant basophilic or eosinophilic cytoplasm with grade 1-2 atypia (grade 3 atypia warrants a designation of intraepithelial carcinoma, with marked nuclear enlargement, hyperchromasia, and prominent nucleoli, often with mitotic figures); proliferative areas with atypical architecture and cytology constitute >10% of the tumor; areas of cystadenoma with small basal nuclei may be present	2. Architectural complexity with glandular crowding and cystic areas with epithelial stratification, intraglandular papillary growth, and detached epithelial clusters; mucinous epithelial lining displays abundant basophilic or eosinophilic cytoplasm with grade 1-2 atypia (grade 3 atypia warrants a designation of intraepithelial carcinoma, with marked nuclear enlargement, hyperchromasia, and prominent nucleoli, often with mitotic figures); proliferative areas with atypical architecture and cytology constitute >10% of the tumor; areas of cystadenoma with small basal nuclei may be present
	3. Microinvasion is characterized by budding of single and small nests of atypical mucinous epithelium haphazardly into the stroma; each focus <5 mm in diameter; multiple foci of microinvasion permissible; stromal reaction may be myxoid or fibrous, sometimes with mucin dissection in stroma; mucin granulomas often present (Figs. 5.11.1 5.11.2, 5.11.3, 5.11.4, 5.11.5); per the 2014 WHO Classification, cases with marked cytologic atypia should be classified as “microinvasive carcinoma,” but the exact criteria for distinction from microinvasion are ill defined	3. Areas of gland rupture display mucin dissection through the stroma (pseudomyxoma ovarii) (Figs. 5.11.6 5.11.7, 5.11.8) and inflammation (Figs. 5.11.8 and 5.11.9); mucin granulomas characterized by clustered foamy macrophages are often present and may also contain lymphocytes and multinucleated giant cells; isolated or clustered mucinous epithelial cells or disrupted glands may be present within the stroma (Fig. 5.11.7); features of infarction may be present; stromal reaction may be fibrous
	4. Tumors should be well sampled to exclude more extensive areas of invasion	4. Tumors should be well sampled to exclude invasion
Special studies	Not useful in this differential	Not useful in this differential
Treatment	USO	USO
Prognosis	Rare cases recur or metastasize; virtually 100% survival if well sampled (two blocks/centimeter maximum diameter) and metastatic carcinoma to the ovary is rigorously excluded	Benign

Figure 5.11.1 Atypical proliferative (borderline) mucinous tumor with microinvasion displays a haphazard infiltrative pattern of angulated glands in a reactive desmoplastic stroma. Noninvasive component is at left.

Figure 5.11.2 Same case as Figure 5.11.1 displaying infiltrative glands with moderate cytologic atypia.

Figure 5.11.3 Atypical proliferative (borderline) mucinous tumor with microinvasion with several irregularly shaped glands in a reactive stroma.

Figure 5.11.4 Atypical proliferative (borderline) mucinous tumor with microinvasion, same case as Figure 5.11.3, displaying moderate cytologic atypia.

Figure 5.11.5 Atypical proliferative (borderline) mucinous tumor with microinvasion shows a cluster of small glands with an infiltrative pattern in the center; noninvasive component is seen at top and bottom.

Figure 5.11.6 Atypical proliferative (borderline) mucinous tumor with gland rupture at low magnification shows large pools of mucin dissecting the stroma (pseudomyxoma ovarii).

Figure 5.11.7 Atypical proliferative (borderline) mucinous tumor with a solitary disrupted gland accompanied by mucin dissection. Note chronic inflammation and numerous foamy macrophages surrounding space at top left.

Figure 5.11.8 High magnification of stromal reaction to gland rupture with mucin dissection showing edema and chronic inflammation; disrupted glandular epithelium partially lines space.

Figure 5.11.9 Round glands within site of rupture are associated with marked acute and chronic inflammation.

5.12 ATYPICAL PROLIFERATIVE (BORDERLINE) MUCINOUS TUMOR (APMT), INTESTINAL TYPE VS. INVASIVE MUCINOUS CARCINOMA, PRIMARY OVARIAN

	Atypical Proliferative (Borderline) Mucinous Tumor, Intestinal Type	Invasive Mucinous Carcinoma, Primary Ovarian
Age	Mean 50 years	Mean 50 years
Location	Within ovary	Within ovary
Symptoms	Pelvic/abdominal pain, increasing abdominal girth	Pelvic/abdominal pain, increasing abdominal girth
Signs	Large pelvic/abdominal mass	Large pelvic/abdominal mass
Etiology	Arise in mucinous cystadenomas; KRAS mutations; rarely BRAF mutations	Arise from mucinous cystadenomas through APMT; KRAS mutations; rarely BRAF mutations
Gross and histology	1. Nearly always unilateral, mean size 22 cm; grossly similar to mucinous cystadenomas, with large, mucin-filled cysts; papillary growths sometimes arise in cyst walls	1. Nearly always unilateral, mean size 21 cm; 90% stage I; grossly similar to mucinous cystadenomas and APMT, with large, mucinfilled cysts; papillary growths sometimes arise in cyst walls
	2. Architectural complexity with glandular crowding and cystic areas with epithelial stratification, intraglandular papillary growth, and detached epithelial clusters. Mucinous epithelial lining displays abundant basophilic or eosinophilic cytoplasm with grade 1-2 atypia (grade 3 atypia warrants a designation of intraepithelial carcinoma, with marked nuclear enlargement, hyperchromasia, and prominent nucleoli, often with mitotic figures); proliferative areas with atypical architecture and cytology constitute >10% of the tumor. Areas of cystadenoma with small basal nuclei may be present (Figs. 5.12.1 5.12.2, 5.12.3, 5.12.4, 5.12.5); tumors should be well sampled to exclude invasion	2. Complex papillary and/or glandular growth (including back-to-back glands without intervening stroma and/or presence of anastomosing epithelium) exceeding that seen in APMT reflects invasion in the confluent/expansile pattern (Figs. 5.12.6 5.12.7, 5.12.8); less commonly, a haphazard infiltrative pattern of small and moderately sized mucinous glands, nests, and single cells reflect destructive stromal invasion (Figs. 5.12.9 and 5.12.10); a background of cystadenoma/APMT may be present (≥5 mm of confluent/invasive growth is required for distinguishing carcinoma from APMT); mucinous epithelial lining displays abundant basophilic or eosinophilic cytoplasm; invasive areas may display range of atypia (grade 1-3)
Special studies	Not useful in this differential	Not useful in this differential
Treatment	USO	Staging (with debulking when indicated) (omission of lymph nodes acceptable); chemotherapy (in neoaduvant or adjuvant setting) except for stage IA/B low-grade tumors
Prognosis	Benign	95% survival for stage I; advanced stage, which is rare, has dismal prognosis

Figure 5.12.1 Atypical proliferative (borderline) mucinous tumor showing multicystic appearance and epithelial stratification. Glands in stroma at the bottom of the photograph represent tangential sectioning of the base of the mucinous tumor rather than invasive carcinoma.

Figure 5.12.2 Atypical proliferative (borderline) mucinous tumor (same case as Fig. 5.12.1) with glands separated by unaltered fibromatous stroma.

Figure 5.12.3 Atypical proliferative (borderline) mucinous tumor displaying villous architecture.

Figure 5.12.4 Atypical proliferative (borderline) mucinous tumor with moderate cytologic atypia and focal detachment of cell clusters.

Figure 5.12.5 Atypical proliferative (borderline) mucinous tumor with intestinal-type mucinous epithelium with goblet cells and mild cytologic atypia.

Figure 5.12.6 Mucinous carcinoma displaying confluent pattern of invasion, which is best appreciated at low magnification.

Figure 5.12.7 Mucinous carcinoma with confluent/expansile pattern of invasion appreciated at low magnification.

Figure 5.12.8 Mucinous carcinoma (confluent pattern) displaying intestinal-type mucinous epithelium with complex glandular and papillary pattern.

Figure 5.12.9 Mucinous carcinoma with haphazard infiltrative pattern of rounded and angulated glands of varying sizes. When this pattern is encountered in an ovarian mucinous tumor, a metastasis with secondary ovarian involvement must be excluded.

Figure 5.12.10 Same case as Figure 5.12.9 showing moderate cytologic atypia in the infiltrative mucinous glands.

5.13 ATYPICAL PROLIFERATIVE (BORDERLINE) ENDOMETRIOID TUMOR (APET) VS. ENDOMETRIOID CARCINOMA, FIGO GRADE 1

	Atypical Proliferative (Borderline) Endometrioid Tumor	Endometrioid Carcinoma, FIGO Grade 1
Age	Mean 53 years	Mean 55-58 years
Location	Within ovary	Within ovary
Symptoms	Pelvic/abdominal pain, vaginal bleeding	Pelvic pain, increasing abdominal girth, bloating, early satiety, vaginal bleeding, urinary symptoms
Signs	Pelvic mass; over a third have endometrial hyperplasia or carcinoma	Pelvic/abdominal mass, ascites
Etiology	Endometriosis; CTNNB1 mutation in cases associated with carcinoma	Endometriosis; germline hMLH1 or hMSH2 mutation (Lynch syndrome); PTEN, β-catenin (CTNNB1), KRAS, ARID1A, and PIK3CA mutation
Gross and histology	1. Mean 9 cm; 95% unilateral, 2% with peritoneal implants; solid or cystic, often with old blood reflecting endometriosis	1. Usually unilateral, stage I in almost half; mean 15 cm; cystic or cystic and solid; cysts contain dark brown viscous fluid (old blood +/- mucus); papillary or nodular growths arise from cyst lining
	2. Two major growth patterns: adenofibromatous pattern displays crowded, often back-to-back endometrioid glands (Figs. 5.13.1 5.13.2, 5.13.3); intracystic papillary/glandular pattern resembles endometrial hyperplasia or grade 1 carcinoma	2. Architecturally well differentiated with confluent glandular epithelial proliferation resembling endometrial endometrioid carcinoma; cribriform (Figs. 5.13.4 5.13.5, 5.13.6, 5.13.7), villoglandular, and occasionally solid patterns; less commonly with infiltrative pattern of glands and nests. Confluence or invasion exceeds 5 mm
	3. Glands and papillae are lined by tall columnar cells with sharp luminal margins, mild to moderate cytologic atypia, round to ovoid nuclei, and sparse mitotic activity (Fig. 5.13.3)	3. Tall columnar epithelium with sharp luminal gland margins, round to ovoid nuclei with hyperchromasia, and prominent nucleoli (Figs. 5.13.6 and 5.13.7); mitotic activity variable, often high
	4. Endometriosis is commonly present, and features often suggest an origin in the endometriosis. Squamous (morular) metaplasia is commonly seen	4. Squamous differentiation in half; adenofibromatous component often present; associated endometriosis is present in majority and often shows atypia, hyperplasia, and other features reflecting origin within endometriotic cyst or associated APET
	5. There may be glandular confluence or microinvasion, which does not exceed 5 mm	5. Secretory, ciliated, and sertoliform variants may occur
Special studies	Not useful in this differential	Not useful in this differential
Treatment	BSO +/- TAH	Staging (with debulking when indicated), chemotherapy except for low-grade stage IA/B; hormonal suppression often used for recurrence
Prognosis	<1% recur; no deaths reported	Stage I >90% survival; stage-stratified analyses show somewhat better prognosis compared to high-grade serous carcinoma in advanced stage

Figure 5.13.1 Atypical proliferative (borderline) endometrioid tumor displays an adenofibromatous appearance with gland crowding but lacking confluence.

Figure 5.13.2 Atypical proliferative (borderline) endometrioid tumor, same case as Figure 5.13.1, with crowded endometrioid glands.

Figure 5.13.3 Atypical proliferative (borderline) endometrioid tumor, same case as Figure 5.13.1, with mild cytologic atypia of endometrioid epithelium.

Figure 5.13.4 Low-grade endometrioid carcinoma with infiltrative pattern of cribriform glands.

Figure 5.13.5 Low-grade endometrioid carcinoma with cribriform pattern showing sharp luminal margins and moderate cytologic atypia.

Figure 5.13.6 Same case as Figure 5.13.5 displaying moderate cytologic atypia.

Figure 5.13.7 Same case as Figure 5.13.4 displaying sharp luminal margins and mild to moderate cytologic atypia.

5.14 ENDOMETRIOID CARCINOMA VS. METASTATIC COLONIC CARCINOMA

	Endometrioid Carcinoma	Metastatic Colonic Carcinoma
Age	Mean 55-58 years	Mean 48 years from undiagnosed colon cancers; mean 61 years from known colon cancers
Location	Within ovary	Within ovary and on ovarian surface
Symptoms	Pelvic pain, increasing abdominal girth, bloating, early satiety, vaginal bleeding, urinary symptoms	Pelvic/abdominal pain; a few patients have blood in stool
Signs	Pelvic/abdominal mass, ascites	Pelvic/abdominal mass; serum CA125 or CEA may be elevated; primary colonic tumor may be undiagnosed
Etiology	Endometriosis; germline hMLH1 or hMSH2 mutation (Lynch syndrome); PTEN, β–catenin (CTNNB1), KRAS, ARID1A, and PIK3CA mutations	Metastasis from primary colorectal carcinoma with secondary involvement of ovary A subset can be associated with Lynch syndrome
Gross and histology	1. Usually unilateral, stage I in almost half; mean 15 cm; cystic or cystic and solid; cysts contain dark brown viscous fluid (old blood with mucus); papillary or nodular growths arise from cyst lining	1. Mean 13-14 cm, 40% bilateral; typically cystic; not infrequently unilateral and >10 cm
	2. Most are architecturally well differentiated with confluent glandular epithelial proliferation resembling endometrial endometrioid carcinoma; cribriform, villoglandular, and occasionally solid patterns; less commonly with infiltrative pattern of glands, nests, and solid masses with jagged edges (Figs. 5.14.1 5.14.2, 5.14.3, 5.14.4)	2. Confluent invasive well-differentiated glandular architecture with garland pattern of dirty necrosis; may have infiltrating pattern of invasion with desmoplasia; tumor on ovarian surface and/or nodular growth within parenchyma (Figs. 5.14.6 5.14.7, 5.14.8, 5.14.9)
	3. Tall columnar epithelium with sharp luminal gland margins, round to ovoid nuclei with hyperchromasia, prominent nucleoli (Figs. 5.14.3 5.14.4, 5.14.5); mitotic activity variable, often high; necrosis may occasionally be present (Figs. 5.14.1 5.14.2, 5.14.3, 5.14.4); mucinous differentiation can be present	3. May be typical or mucinous type of colon carcinoma; typical type most often mimics endometrioid carcinoma (Figs. 5.14.8 5.14.9, 5.14.10)
	4. Squamous differentiation in half; adenofibromatous component often present; associated endometriosis is present in majority and often shows atypia, hyperplasia, and other features reflecting origin within endometriotic cyst or associated atypical proliferative (borderline) endometrioid tumor	4. No squamous differentiation
	5. Secretory, ciliated, and sertoliform variants may occur	5. No secretory, ciliated, or sertoliform differentiation
Special studies	CK7 patchy or diffuse; CK20 negative, focal, or patchy (extent of CK7 > CK20); CDX-2 negative (may be [+] in a component with mucinous differentiation); ER/PR+; usually PAX8+	CK20 usually diffuse; CDX-2 usually diffuse; minority are CK7+ (ascending colon and poorly differentiated tumors); in general, extent of CK20 > CK7; ER/PR-, PAX8-
Treatment	Staging (with debulking when indicated); chemotherapy (in neoaduvant or adjuvant setting) except for low-grade stage IA/B; hormonal suppression often used for recurrence	As per advanced-stage colon carcinoma
Prognosis	Stage I >90% survival	The median survival for stage IV colon carcinoma can be over 2 years, particularly when isolated metastases (usually liver) can be completely resected

Figure 5.14.1 Endometrioid carcinoma displaying a haphazard infiltrative pattern of rounded, ovoid, and focally angulated islands of cribriform glands.

Figure 5.14.2 Low-grade endometrioid carcinoma with infiltrative pattern of smoothly contoured islands of cribriform glands. Necrosis is present within the larger glands toward top left.

Figure 5.14.3 Endometrioid carcinoma. Same case as Figure 5.14.1 showing tall columnar stratified epithelium closely resembling endometrial endometrioid carcinoma. Necrosis is present within glands.

Figure 5.14.4 Low-grade endometrioid carcinoma. Same case as Figure 5.14.2 with cribriform glands lined by tall columnar epithelium with sharp luminal margins. Necrosis is present in the center.

Figure 5.14.5 Endometrioid carcinoma with round to ovoid nuclei with moderate atypia.

Figure 5.14.6 Low magnification of metastatic colonic carcinoma showing discrete nodules of carcinoma with focal garland pattern of necrosis left of center.

Figure 5.14.7 Metastatic colonic adenocarcinoma with lower left field displaying abundant dirty necrosis and irregular gland aggregates at top right.

Figure 5.14.8 Same case as Figure 5.14.7 showing cribriform colonic-type glands associated with extracellular mucin and necrosis.

Figure 5.14.9 Same case as Figure 5.14.6 showing garland pattern with central dirty necrosis, surrounded by undulating malignant colonic-type epithelium.

Figure 5.14.10 Same case as Figure 5.14.7 showing goblet cells typical of colonic adenocarcinoma, moderate to severe atypia, and necrosis.

5.15 ENDOMETRIOID CARCINOMA VS. MUCINOUS CARCINOMA, PRIMARY OVARIAN

	Endometrioid Carcinoma	Mucinous Carcinoma, Primary Ovarian
Age	Mean 55-58 years	Mean 50 years
Location	Within ovary	Within ovary
Symptoms	Pelvic pain, increasing abdominal girth, bloating, early satiety, vaginal bleeding, urinary symptoms	Pelvic/abdominal pain, increasing abdominal girth
Signs	Pelvic/abdominal mass, ascites	Large pelvic/abdominal mass
Etiology	Endometriosis; germline hMLH1 or hMSH2 mutation (Lynch syndrome); PTEN, β–catenin (CTNNB1), KRAS, ARID1A, and PIK3CA mutations	Arise from mucinous cystadenomas through atypical proliferative (borderline) mucinous tumors (APMT); KRAS mutations; rarely BRAF mutations
Gross and histology	1. Usually unilateral, stage I in almost half; mean 15 cm; cystic or cystic and solid; cysts contain dark brown viscous fluid (old blood +/- mucus); papillary or nodular growths arise from cyst lining	1. Nearly always unilateral, mean size 21 cm; 90% stage I; grossly similar to mucinous cystadenomas and APMT, with large, mucinfilled cysts; papillary growths sometimes arise in cyst walls
	2. Most are architecturally well differentiated with confluent glandular epithelial proliferation resembling endometrial endometrioid carcinoma; cribriform, villoglandular, and occasionally solid patterns (Figs. 5.15.1 5.15.2, 5.15.3); less commonly with infiltrative pattern of glands, nests, and solid masses with jagged edges	2. Most are architecturally well differentiated with complex papillary and glandular growth; the extent and complexity reflect invasion in the confluent/expansile pattern (Figs. 5.15.4 5.15.5, 5.15.6); less commonly, a haphazard infiltrative pattern of small- and moderately sized mucinous glands, nests, and single cells reflects destructive stromal invasion; ≥5 mm of confluent or invasive growth is required for a diagnosis of carcinoma
	3. Tall columnar epithelium with sharp luminal gland margins, round to ovoid nuclei with hyperchromasia, and prominent nucleoli (Fig. 5.15.3); mitotic activity variable, often high; foci of intracellular and extracellular mucin may occasionally be present	3. Mucinous epithelial lining displays abundant basophilic or eosinophilic cytoplasm (Figs. 5.15.6 and 5.15.7); areas of cystadenoma display small basal nuclei; in other areas, there is a spectrum of atypia present from mild to severe, with nuclear enlargement, hyperchromasia, prominent nucleoli, and pseudostratification, often with numerous mitotic figures; extracellular mucin is often seen within glands
	4. Squamous differentiation in half (Fig. 5.15.2); adenofibromatous component may be present; associated endometriosis is present in majority and often shows atypia, hyperplasia, and other features reflecting origin within endometriotic cyst or associated atypical proliferative (borderline) endometrioid tumor	4. Endometriosis may occasionally be present; adenofibromatous background and squamous differentiation absent
	5. Secretory, ciliated, and sertoliform variants may occur	5. No secretory, ciliated, or sertoliform differentiation
Special Studies	• ER/PR+; PAX8 usually (+)	• ER/PR- (very focal weak staining is seen occasionally); PAX8 usually (-) but can be (+) in a subset of cases
	• Loss of staining for DNA mismatch repair proteins (MLH1, MSH2, PMS2, MSH6) in a subset
Treatment	Staging (with debulking when indicated); chemotherapy (in neoaduvant or adjuvant setting) except for low-grade stage IA/B; hormonal suppression may be used for recurrence	Staging (with debulking when indicated) (omission of lymph nodes acceptable); chemotherapy (in neoaduvant or adjuvant setting) except for low-grade stage IA/B tumors; appendectomy
Prognosis	Stage I >90% survival	95% survival for stage I; advanced stage, which is rare, has dismal prognosis

Figure 5.15.1 Endometrioid carcinoma with confluent pattern displaying cribriform architecture.

Figure 5.15.2 Endometrioid carcinoma showing infiltrating glandular pattern, squamous differentiation, and desmoplastic stroma.

Figure 5.15.3 Endometrioid carcinoma displaying invasive cribriform glands with tall columnar epithelium and sharp luminal margins resembling endometrial endometrioid adenocarcinoma.

Figure 5.15.4 Confluent or expansile pattern of invasive mucinous carcinoma with complex and interconnecting glands and exclusion of stroma.

Figure 5.15.5 Confluent pattern of invasive mucinous carcinoma with very minimal intervening stroma and abundant intracytoplasmic mucin.

Figure 5.15.6 Mucinous carcinoma displaying abundant amphophilic to eosinophilic cytoplasm in cribriform glands.

Figure 5.15.7 Same case as Figure 5.15.6 displaying moderate cytologic atypia and both intracellular and extracellular mucin.

5.16 ENDOMETRIOID CARCINOMA, SERTOLIFORM VARIANT VS. SERTOLI CELL TUMOR

	Endometrioid Carcinoma, Sertoliform Variant	Sertoli Cell Tumor
Age	60-70 years	Mean 30 years
Location	Within ovary	Within ovary
Symptoms	Pelvic pain, increasing abdominal girth, bloating, early satiety, vaginal bleeding, urinary symptoms	Pelvic/abdominal pain, swelling, vaginal bleeding
Signs	Pelvic/abdominal mass; postmenopausal bleeding; may have virilization	40% have estrogenic manifestations
Etiology	Endometriosis; PTEN, β-catenin (CTNNB1), KRAS, ARID1A, and PIK3CA mutations	Rarely seen in patients with Peutz-Jeghers syndrome; DICER1 mutations
Gross and histology	1. Predominantly solid, focally cystic; 10% bilateral; mean 13.6 cm; most commonly stage I	1. Unilateral, stage I, mean 8-9 cm
	2. Solid or hollow slender anastomosing cords with stratified appearance, merge with tubules; low-grade nuclear features (in general, the level of nuclear atypia is greater than that seen in Sertoli cell tumor); occasionally, secretions may be present within gland lumens; abundant fibromatous stroma, occasionally with calcification; stroma often luteinized (Figs. 5.16.1 and 5.16.2)	2. Uniform tubular pattern; hollow tubules lined by tall cuboidal or columnar cells; solid tubules may be elongated, round, or ovoid; closely packed solid tubules may mimic diffuse sheets; less commonly cords, trabecular, and spindled patterns (Figs. 5.16.6 5.16.7, 5.16.8, 5.16.9); no secretions within tubule lumens
	3. Areas of usual low-grade endometrioid carcinoma typically merge with sertoliform areas; mucin may be present at apical cell borders; occasional cilia may be seen (Figs. 5.16.3 5.16.4, 5.16.5)	3. Bland round to ovoid uniform nuclei, pale to eosinophilic cytoplasm, mitotically inactive (Fig. 5.16.10); rare lipid-rich and oxyphilic variants
	4. Background endometriosis, squamous differentiation, or adenofibromatous component may be present (Fig. 5.16.3)	4. No endometriosis in the background; squamous differentiation is not seen
Special studies	• CK7+, EMA+, ER/PR+, usually PAX8+	• CK7-, EMA-, ER/PR+, PAX8- (other cytokeratin stains are nonspecific as they can be positive in Sertoli cell tumor)
	• WT1, inhibin, and calretinin are usually (-) but may be focally (+) or strong (+) in small minority; SF-1 negative	• WT1+, SF-1+, inhibin+, calretinin+
	• Loss of staining for DNA mismatch repair proteins (MLH1, MSH2, PMS2, MSH6) in a subset of cases
Treatment	Limited data; presumed same as usual endometrioid carcinoma (staging (with debulking when indicated), chemotherapy (in adjuvant or neoadjuvant setting) except for stage IA/IB low-grade tumors; hormonal suppression may be used for recurrence)	USO
Prognosis	Based on limited data, same as stage-stratified usual endometrioid carcinoma	Usually benign

Figure 5.16.1 Endometrioid carcinoma, sertoliform variant, displaying solid nests and cords resembling Sertoli cell tumor.

Figure 5.16.2 Endometrioid carcinoma, sertoliform variant (same case as Fig. 5.16.1), displaying cords of columnar cells with elongated, ovoid nuclei.

Figure 5.16.3 Endometrioid carcinoma, usual type, showing a haphazard infiltrative pattern of variably sized glands, which focally show squamous differentiation.

Figure 5.16.4 Endometrioid carcinoma, usual type, showing cribriform features and tall columnar epithelium lining glands with sharp luminal margins.

Figure 5.16.5 Endometrioid carcinoma, usual type, with columnar epithelium lining glands with sharp luminal margins.

Figure 5.16.6 Sertoli cell tumor with nodular groups of smoothly contoured nests and islands.

Figure 5.16.7 Sertoli cell tumor displaying crowded small tubules and cords with well-oriented basal nuclei.

Figure 5.16.8 Sertoli cell tumor with crowded tubules and some degree of architectural complexity.

Figure 5.16.9 Sertoli cell tumor with back-to-back tubules mimicking a confluent pattern of endometrioid carcinoma.

Figure 5.16.10 Sertoli cell tumor with open and solid tubules lined by columnar cells with round to ovoid nuclei and pale cytoplasm (same case as Fig. 5.16.9).

5.17 ENDOMETRIOID CARCINOMA WITH SPINDLED SQUAMOUS COMPONENT VS. CARCINOSARCOMA (MMMT)

	Endometrioid Carcinoma with Spindled Squamous Component	Carcinosarcoma (MMMT)
Age	Mean 61 years	Mean 65-66 years
Location	Within ovary	Ovarian surface and within stroma
Symptoms	Pelvic pain/dysmenorrhea	Pelvic pain, increasing abdominal girth, bloating, early satiety, urinary symptoms
Signs	Pelvic mass	Pelvic/abdominal mass, ascites
Etiology	Endometriosis; PTEN, β-catenin (CTNNB1), KRAS, ARID1A, and PIK3CA mutations	Majority derive from serous tubal intraepithelial carcinoma, usually of fimbrial origin; nearly all have TP53 mutations
Gross and histology	1. Mean 13 cm, solid and cystic, about one-third stage I	1. Ovaries normal sized or slightly enlarged in one-third to one-half of cases with subcentimeter surface nodules; remaining show enlarged solid and/or cystic ovaries, 8-10 cm; fallopian tube fimbriae may be prominent and tumorous and may be splayed across ovarian surface; usually bilateral adnexal involvement and nearly always with peritoneal carcinomatosis or extensive bowel invasion
	2. Extensive spindle cell component, usually >50% of tumor, in nests, creating a lobulated appearance; less commonly, diffuse spindle cell pattern; may display whorls and focal palisading (Figs. 5.17.1 5.17.2, 5.17.3); squamous component may incite a foreign body-type giant cell reaction	2. Epithelial component usually displays high-grade serous patterns with papillary, glandular, and solid patterns, commonly intermixed; less commonly thick urothelial-like papillae; endometrioid patterns may be present (Figs. 5.17.6 5.17.7, 5.17.8)
	3. Typical endometrioid glands present in all cases; in half, discrete component of typical low-grade endometrioid carcinoma (Figs. 5.17.3 5.17.4, 5.17.5); half have sertoliform areas	3. Large epithelial cells with marked atypia, often with bizarre nuclear forms; large prominent nucleoli (Fig. 5.17.8) and abundant mitotic activity with abnormal forms
	4. Nuclear features of the spindle cells similar to those of the endometrioid glands, generally low grade (Fig. 5.17.4); usually low mitotic index	4. Sarcomatous component with high-grade spindle cell differentiation with high mitotic activity, marked cytologic atypia (Figs. 5.17.8 5.17.9, 5.17.10); myxoid or small cell areas may be present; heterologous elements commonly present (>50%), most often cytologically malignant cartilage, rhabdomyoblasts, occasionally osteoid, and liposarcoma
Special studies	• CK7+, ER/PR+, EMA+; WT1, and p16 are usually (-) but may be focally (+) or strongly (+) in small minority; usually nonaberrant pattern of p53 expression	• Epithelial component: aberrant p53 expression; CK7+, p16+ (diffuse), WT1+, CAM5.2+, and ER+ in majority; sarcomatous component generally has similar profile but may stain more weakly or focally for epithelial markers
	• Loss of staining for DNA mismatch repair proteins (MLH1, MSH2, PMS2, MSH6) in a subset of cases
Treatment	Staging (with debulking when indicated); chemotherapy (in neoaduvant or adjuvant setting) except for low-grade stages IA/IB; hormonal therapy may be used for recurrences	Staging (with debulking when indicated); chemotherapy (in neoaduvant or adjuvant setting)
Prognosis	Presumed similar to usual endometrioid carcinoma: stage I >90% survival; stage-stratified analyses show somewhat better prognosis compared to high-grade serous carcinoma in advanced stage	Stage III patients have 5-year survival of 20%-25%

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Tags: Differential Diagnoses in Surgical Pathology: Gynecologic Tract

Sep 25, 2018 | Posted by drzezo in PATHOLOGY & LABORATORY MEDICINE | Comments Off

Basicmedical Key

Fastest Basicmedical Insight Engine

Ovary

Like this:

Related

Stay updated, free articles. Join our Telegram channel

Full access? Get Clinical Tree

Basicmedical Key

Fastest Basicmedical Insight Engine

Ovary

Share this:

Like this:

Related

Related posts:

Stay updated, free articles. Join our Telegram channel

Full access? Get Clinical Tree