Uterus

Abstract

This chapter is an overview of frequently used markers in the differential diagnosis of both common and less common tumors of the uterine cervix and corpus, with a focus on the effective markers employed to differentiate adenocarcinoma of the endocervix versus endometrium, low-grade versus high-grade endometrial neoplasms, benign versus malignant mimics of cervical and endometrial lesions. Other useful panels in the differential diagnosis of undifferentiated tumors of the uterine corpus and gestational trophoblastic lesions in addition to the less common carcinomas of the cervix are also addressed. There are 47 tables in this chapter with immunohistochemical markers answering questions that may arise when examining hematoxylin and eosin-stained sections. A summary of useful and frequently used markers with potential pitfalls is also provided. The effective diagnostic panels of antibodies for several entities are highlighted in several tables.

Frequently Asked Questions

• 1. Summary of applications and limitations of useful markers (Table 20.1)

• 2. Summary of useful markers in common tumors (Table 20.2)

• 3. Markers for normal and non-neoplastic lesions of the cervix (Table 20.3)

• 4. Markers for normal and non-neoplastic lesions of the endometrium (Table 20.4)

• 5. Markers for cervical high-grade squamous intraepithelial lesion (Table 20.5)

• 6. Markers for in situ endocervical adenocarcinoma (Table 20.6)

• 7. Markers for invasive squamous cell carcinoma of cervix (Table 20.7)

• 8. Markers for invasive endocervical (mucinous) and endometrioid adenocarcinoma of cervix (Table 20.8)

• 9. Markers for in situ and invasive gastric-type endocervical adenocarcinoma (Table 20.9)

• 10. Markers for in situ and invasive intestinal-type endocervical adenocarcinoma (Table 20.10)

• 11. Markers for minimal deviation adenocarcinoma of the cervix (Table 20.11)

• 12. Markers for small cell poorly differentiated carcinoma of the uterine cervix (Table 20.12)

• 13. Markers for mesonephric adenocarcinoma of cervix (Table 20.13)

• 14. Markers for endometrioid adenocarcinoma of the endometrium (Table 20.14)

• 15. Markers for benign hyperplasia and endometrioid intraepithelial neoplasia (Table 20.15)

• 16. Markers for serous carcinoma of the endometrium and putative precursors EIC (Table 20.16)

• 17. Markers for uterine serous papillary carcinoma and ovarian serous papillary carcinoma (Table 20.17)

• 18. Markers for clear cell carcinoma of the endometrium (Table 20.18)

• 19. Markers for carcinosarcoma of the endometrium (Table 20.19)

• 20. Markers for atypical polypoid adenomyoma (Table 20.20)

• 21. Markers for stromal nodule and low-grade endometrial stromal sarcoma (Table 20.21)

• 22. Markers for high-grade endometrial stromal sarcoma (Table 20.22)

• 23. Markers for undifferentiated uterine sarcoma (Table 20.23)

• 24. Markers for low-grade Müllerian adenosarcoma (stromal component) (Table 20.24)

• 25. Markers for uterine smooth muscle tumors (Table 20.25)

• 26. Markers for adenomatoid tumor (Table 20.26)

• 27. Markers for PEComas (Table 20.27)

• 28. Markers for uterine tumor resembling ovarian sex cord tumor (Table 20.28)

• 29. Markers for gestational trophoblastic lesions (Table 20.29)

• 30. Differentiating high-grade SIL of cervix from benign mimics and low-grade SIL (Table 20.30)

• 31. Differentiating in situ adenocarcinoma of cervix from endometriosis (Table 20.31)

• 32. Differential diagnosis of cervical microglandular hyperplasia (Table 20.32)

• 33. Endocervical versus low-grade endometrial adenocarcinoma (Table 20.33)

• 34. Differentiating epithelioid trophoblastic tumor and cervical squamous cell carcinoma (Table 20.34)

• 35. Differentiating adenoid cystic, adenoid basal, basaloid squamous cell, and small cell neuroendocrine carcinomas (Table 20.35)

• 36. Arias-Stella reaction and clear cell carcinoma of endometrium (Table 20.36)

• 37. Endometrial adenocarcinoma and carcinosarcoma (MMMT) (Table 20.37)

• 38. Clear cell carcinoma versus malignant mimics with clear cytoplasm (glycogen-rich squamous cell carcinoma, clear cell sarcoma, metastatic renal cell carcinoma, and yolk sac tumor) (Table 20.38)

• 39. Endometrial serous versus endometrioid versus clear cell adenocarcinoma (Table 20.39)

• 40. Useful markers in the differential diagnosis of endometrial undifferentiated carcinoma (Table 20.40)

• 41. Differentiating leiomyosarcoma and endometrial stromal sarcoma (Table 20.41)

• 42. Differentiating leiomyosarcoma and PEComa (Table 20.42)

• 43. Differentiating leiomyosarcoma, gastrointestinal stromal tumor, inflammatory myofibroblastic tumor, and spindle cell rhabdomyosarcoma (Table 20.43)

• 44. Complete hydatidiform mole and partial hydatidiform mole (Table 20.44)

• 45. Epithelioid trophoblastic tumor and poorly differentiated endometrial adenocarcinoma (Table 20.45)

• 46. Differentiating placental site trophoblastic tumors and mimics (exaggerated placental site, epithelioid trophoblastic tumor, choriocarcinoma, epithelioid smooth muscle tumor, and metastatic carcinoma) (Table 20.46)

• 47. Summary of common markers of primary uterine carcinoma and the more common metastatic carcinomas (Table 20.47)

Table 20.1 Summary of applications and limitations of useful markers

Table 20.2 Summary of useful markers in common tumors (most commonly used markers are shaded)

Table 20.3 Markers for normal and non-neoplastic lesions of the cervix

Fig. 20.1

Mesonephric remnant hyperplasia (a), with diffuse positive vimentin (b), and luminal CD10 positivity (c). References: [1, 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18, 47, 48]

Table 20.4 Markers for normal and non-neoplastic lesions of the endometrium

Fig. 20.2

Endometrial squamous metaplasia with lack of CEA staining (a), patchy staining pattern with p16 (b), and lack of staining with vimentin in the metaplastic foci (c). References: [5, 8, 10, 17, 49]

Table 20.5 Markers for cervical high-grade squamous intraepithelial lesion

Fig. 20.3

High-grade SIL on hematoxylin and eosin (H&E) (a), with full thickness and intense nuclear staining with p16 (b), and increased Ki-67 proliferative index involving upper layers (c). References: [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18, 47, 48, 50]

Table 20.6 Markers for in situ endocervical adenocarcinoma

Fig. 20.4

Adenocarcinoma in situ of the endocervix on H&E (a), with CEA positive staining (b), diffuse and intense p16 nuclear and cytoplasmic staining (c), and increased Ki-67 proliferative index (d). References: [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18, 51]

Table 20.7 Markers for invasive squamous cell carcinoma of the cervix

Table 20.8 Markers for invasive endocervical (mucinous) and endometrioid adenocarcinoma of cervix

Fig. 20.5

Invasive endocervical adenocarcinoma on H&E (a), with p16 diffuse and intense positive staining (b) and positive inclusions by in situ hybridization for HPV (c). References: [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18, 52]

Table 20.9 Markers for in situ and invasive gastric-type endocervical adenocarcinoma

Table 20.10 Markers for in situ and invasive intestinal-type endocervical adenocarcinoma

Table 20.11 Markers for minimal deviation adenocarcinoma of the cervix

Table 20.12 Markers for small cell poorly differentiated carcinomas of the uterine cervix

Table 20.13 Markers for mesonephric adenocarcinoma of cervix

Fig. 20.6

Mesonephric carcinoma on H&E (a) and positive vimentin (b). References: [67,68,69,70]

Table 20.14 Markers for endometrioid adenocarcinoma of the endometrium

Fig. 20.7

Intense vimentin staining in endometrioid adenocarcinoma. References: [1, 34, 61, 71,72,73,74,75,76,77,78,79,80]

Table 20.15 Markers for benign hyperplasia and endometrioid intraepithelial neoplasia

Fig. 20.8

Endometrioid intraepithelial neoplasia (EIN) present in the lower half of the image on H&E (a), with absent PAX2 expression (b), and with absent PTEN expression (c)

Table 20.16 Markers for serous carcinoma of the endometrium and putative precursors EIC

Table 20.17 Markers for uterine serous papillary carcinoma and ovarian serous papillary carcinoma

Table 20.18 Markers for clear cell carcinoma of the endometrium

Table 20.19 Markers for carcinosarcoma of the endometrium^a–c

Table 20.20 Markers for atypical polypoid adenomyoma (most commonly used shaded)

Table 20.21 Markers for stromal nodule and low-grade endometrial stromal sarcoma^a,b

Table 20.22 Markers for high-grade endometrial stromal sarcoma^a,b

Table 20.23 Markers for undifferentiated uterine sarcoma^a

Table 20.24 Markers for low-grade Müllerian adenosarcoma^a (stromal component)

Table 20.25 Markers for uterine smooth muscle tumors

Table 20.26 Markers for adenomatoid tumor

Table 20.27 Markers for PEComas

Table 20.28 Markers for uterine tumor resembling ovarian sex cord tumor

Table 20.29 Markers for gestational trophoblastic lesions

Table 20.30 Differentiating high-grade SIL from benign mimics and low-grade SIL

Table 20.31 Differentiating in situ adenocarcinoma of cervix and endometriosis or tubal-endometrial metaplasia

Table 20.32 Differential diagnosis of cervical microglandular hyperplasia

Table 20.33 Endocervical versus low-grade endometrial adenocarcinoma^a

Table 20.34 Differentiating epithelioid trophoblastic tumor and cervical squamous cell carcinoma

Table 20.35 Differentiating adenoid cystic (ACC), adenoid basal (ABC), basaloid squamous cell (BSCC), and small cell neuroendocrine (SCNEC) carcinomas^a

Table 20.36 Arias-Stella reaction and clear cell carcinoma of endometrium^a

Table 20.37 Endometrial adenocarcinoma and carcinosarcoma (MMMT)^a

Table 20.38 Clear cell carcinoma (CCC) versus malignant mimics with clear cytoplasm [glycogen-rich squamous cell carcinoma (GRSCC), clear cell sarcoma (CCS), metastatic renal cell carcinoma (MCCRCC), and yolk sac tumor (YST)]

Table 20.39 Endometrial serous versus endometrioid versus clear cell adenocarcinoma

Table 20.40 Useful markers in the differential diagnosis of endometrial undifferentiated carcinoma (UC)

Table 20.41 Differentiating leiomyosarcoma and endometrial stromal sarcoma (ESS)

Table 20.42 Differentiating leiomyosarcoma and PEComa

Table 20.43 Differentiating leiomyosarcoma (LMS), gastrointestinal stromal tumor (GIST), inflammatory myofibroblastic tumor (IMT), and spindle cell rhabdomyosarcoma (RHABDO)

Table 20.44 Complete hydatidiform and partial hydatidiform mole

Table 20.45 Epithelioid trophoblastic tumor and poorly differentiated endometrial adenocarcinoma

Table 20.46 Differentiating placental site trophoblastic tumor and mimics [exaggerated placental site, epithelioid trophoblastic tumor, choriocarcinoma, epithelioid smooth muscle tumor, metastatic carcinoma, and malignant melanoma]

Fig. 20.9

Exaggerated placental site on H&E (a) with negative Ki-67 (b) compared to choriocarcinoma on H&E (c) that demonstrates extremely very high Ki-67 proliferative index (d). References: [141,142,143,144,145,146,147,148,149,150,151]

Table 20.47 Summary of common markers of primary uterine carcinoma and the more common metastatic carcinomas (recommended markers highlighted)

Note for All Tables:

“+” – usually greater than 70% of cases are positive; “−” – less than 5% of cases are positive; “+ or −” – usually more than 50% of cases are positive; “− or +” – less than 50% of cases are positive.