Papillary Tubal Hyperplasia

Normal Tubal Mucosa

Age

42 years (mean)

Any age

Location

Fallopian tube lumen and mucosa (does not uniformly involve all tubal mucosa)

Fallopian tube

Symptoms

None; may have coexisting ovarian atypical proliferative (borderline) serous tumor

N/A

Signs

None; usually incidental finding; may have coexisting ovarian atypical proliferative (borderline) serous tumor

N/A

Etiology

Not entirely known; possibly due to inflammatory injury of tubal mucosa; a putative precursor of atypical proliferative (borderline) serous tumor, implants, and endosalpingiosis

N/A

Histology

1. More papillary complexity than normal mucosa, varying from slight to marked (Figs. 7.1.17.1.2, 7.1.3)

1. No papillary complexity (Figs. 7.1.77.1.8, 7.1.9)

2. Epithelial stratification, small papillae (with fibrovascular cores) budding from tubal mucosa, and detached epithelial clusters in tubal lumen (Figs. 7.1.17.1.2, 7.1.3, 7.1.4, 7.1.5)

2. No epithelial stratification, small papillae (with fibrovascular cores) budding from tubal mucosa, or detached epithelial clusters in tubal lumen (Figs. 7.1.77.1.8, 7.1.9, 7.1.10)

3. Psammoma bodies [salpingoliths] (either free floating in tubal lumen or present within stroma or epithelium of mucosa) [Figs. 7.1.47.1.5, 7.1.6]

3. No psammoma bodies (salpingoliths)

4. Background tubal mucosa may have salpingitis or distortion of the plical architecture

4. Background tubal mucosa may have salpingitis or distortion of the plical architecture

Special studies

Immunohistochemistry of no help for this differential diagnosis

Immunohistochemistry of no help for this differential diagnosis

Treatment

None needed

N/A

Prognosis

Benign; risk (if any) of subsequent atypical proliferative (borderline) serous tumor unknown

N/A

Fallopian Tube Papilloma

Well-Differentiated Tubal Neoplasm (FIGO Grade 1 Endometrioid Carcinoma/Low-Grade Serous Carcinoma/Atypical Proliferative [Borderline] Serous Tumor)

Age

Premenopausal

Peri- or postmenopausal

Location

Fallopian tube lumen

Fallopian tube (may also have extratubal involvement)

Symptoms

None expected but data limited; may be incidental finding

Symptoms attributable to adnexal mass

Signs

Small intraluminal mass; hydrosalpinx also may be present

Adnexal mass; extratubal involvement may be present

Etiology

Unknown

Stepwise progression from atypical proliferative (borderline) serous tumor to low-grade serous carcinoma with BRAF/KRAS mutations; evolution from endometriosis to endometrioid carcinoma with CTNNB1, PTEN, PIK3CA, and/or ARID1A mutations and/or microsatellite instability

Histology

1. “Adenomatous” appearance with complex, but orderly, papillary pattern (+/- epithelial stratification); no invasion of underlying tissue; overall architecture vaguely resembles normal mucosa but with much more papillary architecture (Figs. 7.2.17.2.2, 7.2.3); no psammoma bodies (salpingoliths)

1. Hierarchical papillary branching and stratification with detached epithelial tufts in atypical proliferative (borderline) serous tumor (Fig. 7.2.5); stromal invasion with micropapillary architecture in low-grade serous carcinoma (Fig. 7.2.6); +/- psammoma bodies in either type of serous tumor

2. Papillae (with branching) have villous appearance and fine fibrovascular cores (Fig. 7.2.3)

2. FIGO grade 1 endometrioid carcinoma can have villoglandular architecture (Fig. 7.2.7)

3. No glandular confluence, solid architecture, squamous differentiation, or endometriosis

3. Endometrioid carcinoma may have glandular confluence, solid areas (<5% of tumor), squamous differentiation, or endometriosis (Figs. 7.2.8 and 7.2.9)

4. Contains ciliated and secretory cells similar to normal tubal mucosa (Fig. 7.2.4)

4. Tubal-type epithelium will be present in serous tumors; endometrioid carcinoma can have tubal differentiation with ciliated cells although other areas should have classic endometrioid cell types (Fig. 7.2.10)

5. No atypia

5. Some degree of atypia (but not significant) in low-grade serous or endometrioid tumors

6. No mitotic activity

6. Low mitotic index

Special studies

Immunohistochemistry of no help for this differential diagnosis although WT-1 expression is expected

Immunohistochemistry of no help for this differential diagnosis although endometrioid carcinomas usually lack WT-1 expression

Treatment

None needed

Histologic type and stage dependent

Prognosis

Presumably benign (outcome data limited)

Histologic type and stage dependent

Serous Tubal Intraepithelial Carcinoma (STIC)

Nondiagnostic Mucosal Atypia

Age

Usually peri- or postmenopausal

Variable

Location

Tubal mucosa, typically in fimbriated end

Tubal mucosa, +/- fimbriated end

Symptoms

None if an isolated finding; symptoms related to tubal/ovarian/peritoneal high-grade serous carcinoma if concurrently present

None if an isolated finding; symptoms related to an underlying condition leading to salpingectomy

Signs

None if an isolated finding (STIC is microscopic in size and does not create a grossly visible lesion); may be associated with a tubal/ovarian/peritoneal high-grade serous carcinoma

None if an isolated finding (mucosal atypia is microscopic in size and does not create a grossly visible lesion); may be associated with a tubal/ovarian/peritoneal high-grade serous carcinoma

Etiology

Arises from tubal mucosa (presumably as a progression pathway through “p53 signatures” and atypical lesions intermediate between p53 signature and STIC) via TP53 mutations as an early event; +/- BRCA mutations

May be nonneoplastic alteration of reactive/reparative nature or preneoplastic step intermediate between “p53 signature” and STIC; also referred to as tubal intraepithelial lesion in transition and serous tubal intraepithelial lesion

Histology

1. Epithelial stratification; +/- detached clusters (Figs. 7.3.1 and 7.3.2)

1. Can have some degree of epithelial stratification with detached clusters (Figs. 7.3.87.3.9, 7.3.10)

2. Irregular luminal surface (Figs. 7.3.2 and 7.3.3)

2. Can have some degree of irregular luminal surface

3. Nuclear enlargement, nuclear rounding, increased nuclear-to-cytoplasmic ratios, nuclear molding, abnormal chromatin (hyperchromasia, irregularly distributed chromatin, or vesicular chromatin), irregular nuclear membranes, loss of polarity, and/or prominent nucleoli (Figs. 7.3.2 and 7.3.3)

3. Can have some degree of nuclear enlargement, nuclear rounding, increased nuclear-to-cytoplasmic ratios, nuclear molding, abnormal chromatin (hyperchromasia, irregularly distributed chromatin, or vesicular chromatin), irregular nuclear membranes, loss of polarity, and/or prominent nucleoli (Figs. 7.3.9 and 7.3.10)

4. Mitotic activity and/or apoptotic bodies

4. Usually no mitotic activity or apoptotic bodies

5. Loss of ciliated cells

5. Ciliated cells usually present but may be absent

6. Variable combinations of the above features

6. Above features usually not as sufficiently abnormal as in STIC, but morphologic features of mucosal atypia can significantly overlap with the spectrum seen in STIC

Special studies

• p53: abnormal pattern (diffuse moderate-to-strong staining [>75% cells] or complete absence of expression [“null pattern”]) [Figs. 7.3.4 and 7.3.5]

• p53: may have abnormal pattern as in STIC or nonabnormal pattern (focal or patchy staining)

• Ki-67 proliferation index: high (≥10% positive cells) [Figs. 7.3.6 and 7.3.7]

• Ki-67 proliferation index: may have high Ki-67 as in STIC or low index (<10% positive cells)

• To qualify for a diagnosis of STIC, must have significant atypia, abnormal p53 pattern, and high Ki-67 index

• Atypical lesions not qualifying as STIC do not fulfill all three criteria (significant atypia, abnormal p53 pattern, and high Ki-67 index)

Treatment

Limited data, but chemotherapy usually not administered

None

Prognosis

Favorable for isolated STIC, but data in literature are limited (short follow-up, limited number of cases, and existing data heavily weighted toward BRCA germline-mutated rather than sporadic cases); however, a subset of women are at risk for subsequent development of high-grade serous carcinoma (short-term risk appears low for BRCA germline-mutated cases)

Unknown but expected favorable outcome

Serous Tubal Intraepithelial Carcinoma (STIC)

Mucosal Transitional Cell Metaplasia

Age

Usually peri- or postmenopausal

Usually peri- or postmenopausal

Location

Tubal mucosa, typically in fimbriated end

Tubal mucosa, typically in fimbriated end

Symptoms

None if an isolated finding; symptoms related to tubal/ovarian/peritoneal high-grade serous carcinoma if concurrently present

Incidental finding

Signs

None if an isolated finding (STIC is microscopic in size and does not create a grossly visible lesion); may be associated with a tubal/ovarian/peritoneal high-grade serous carcinoma

Incidental finding (microscopic in size; does not create a grossly visible lesion)

Etiology

Arises from tubal mucosa (presumably as a progression pathway through “p53 signatures” and atypical lesions intermediate between p53 signature and STIC) via TP53 mutations as an early event; +/- BRCA mutations

Not applicable; transitional cell metaplasia is commonly found at the fallopian tube-peritoneal junction and may be a normal finding

Histology

1. Epithelial stratification; +/- detached clusters (Figs. 7.4.17.4.2, 7.4.3, 7.4.4, 7.4.5, 7.4.6)

1. Epithelial stratification (Figs. 7.4.77.4.8, 7.4.9)

2. Irregular luminal surface (Figs. 7.4.3, 7.4.5, and 7.4.6)

2. Smooth luminal surface (Figs. 7.4.7 and 7.4.8)

3. Nuclear enlargement, nuclear rounding, increased nuclear-to-cytoplasmic ratios, nuclear molding, abnormal chromatin (hyperchromasia, irregularly distributed chromatin, or vesicular chromatin), irregular nuclear membranes, loss of polarity, and/or prominent nucleoli (Figs. 7.4.47.4.5, 7.4.6)

3. Round to oval and uniform nuclei with pale chromatin, longitudinal nuclear grooves, and abundant cytoplasm; no atypia (Figs. 7.4.8 and 7.4.9)

4. Mitotic activity and/or apoptotic bodies

4. No mitotic activity or apoptotic bodies

5. Loss of ciliated cells

5. Usually lack ciliated cells

6. Variable combinations of the above features

6. Does not show combination of morphologic findings seen in STIC

Special studies

• p53: abnormal pattern (diffuse moderate-to-strong staining [>75% cells] or complete absence of expression [“null pattern”])

• No abnormal p53 pattern

• Ki-67 proliferation index: high (≥10% positive cells)

• No increased Ki-67 index

• To qualify for a diagnosis of STIC, must have significant atypia, abnormal p53 pattern, and high Ki-67 index

• Does not fulfill all three criteria for STIC (significant atypia, abnormal p53 pattern, and high Ki-67 index)

Treatment

Limited data, but chemotherapy usually not administered

None

Prognosis

Favorable for isolated STIC, but data in literature are limited (short follow-up, limited number of cases, and existing data heavily weighted toward BRCA germline-mutated rather than sporadic cases); however, a subset of women are at risk for subsequent development of high-grade serous carcinoma (short-term risk appears low for BRCA germline-mutated cases)

Benign