Cervical small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC) are uncommon but highly aggressive neoplasms. From a diagnostic point of view, there may be problems both in distinguishing these from other neoplasms and in confirming a cervical origin. This is important as management is critically dependent on the correct histologic diagnosis. We undertook a detailed immunohistochemical analysis of a relatively large series of primary cervical SCNEC (n=13) and LCNEC (n=8). Cases were stained with AE1/3, chromogranin, CD56, synaptophysin, PGP9.5, TTF1, p16, p63, CK7, CK20, neurofilament, and CD99. CK20 and neurofilament staining was undertaken to investigate whether some of these neoplasms might exhibit a Merkel cell immunophenotype and CD99 staining to assess whether there is immunohistochemical overlap with neoplasms in the Ewing family of tumors (EFT). For all markers, staining was classified as negative, 1+ (<10% cells immunoreactive), 2+ (10 to 50% cells immunoreactive), or 3+ (>50% cells immunoreactive). Eleven and 6 SCNEC and LCNEC, respectively were positive with AE1/3. Chromogranin, CD56, synaptophysin, and PGP9.5 were positive in 11, 19, 19, and 9 cases, respectively. Altogether 15 cases (71%) (11 SCNEC, 4 LCNEC) exhibited nuclear positivity, often diffuse, with TTF1. All but 1 case was diffusely positive with p16. p63 was positive in 9 cases, including 5 with diffuse nuclear immunoreactivity. Ten and 4 neoplasms were positive with CK7 and CK20, respectively. Neurofilament was positive in 7 tumors. The 4 neoplasms that were CK20 positive were stained with the monoclonal antibody CM2B4, generated against an antigenic epitope on the Merkel cell polyomavirus T antigen; all were negative. CD99 was positive in 6 cases. In 2 cases, adjacent foci of adenocarcinoma in situ (AIS) contained scattered individual chromogranin positive cells, raising the possibility that some cervical neuroendocrine carcinomas arise from neuroendocrine cells in AIS. Four of 13 cases of pure AIS also contained scattered chromogranin positive cells. Our results illustrate that a proportion of cervical neuroendocrine carcinomas are negative with broad spectrum cytokeratins and some of the commonly used neuroendocrine markers. TTF1 positivity is extremely common and may be a useful marker of a neuroendocrine carcinoma. It is of no value in exclusion of a pulmonary primary. p16 is almost always positive in cervical neuroendocrine carcinomas, possibly owing to an association with oncogenic human papillomavirus, although other mechanisms of expression are also possible. Cervical neuroendocrine carcinomas may be p63 positive, illustrating that this marker is not specific for squamous differentiation. CK20 and neurofilament positivity in some cervical neuroendocrine carcinomas is in keeping with a Merkel cell immunophenotype, similar to that described in SCNECs in other organs. However, the absence of staining with CM2B4 argues against a true Merkel cell tumor. CD99 staining in a cervical neuroendocrine car...

The immunophenotype of post-chemotherapy ovarian carcinomas is very similar to that of native untreated tumours, illustrating that CK7, CA125, WT1, ER, p53 and p16 may be of value in identifying residual tumour cells and in subtyping the neoplasm if a pre-chemotherapy biopsy has not been obtained.

Metastatic tumors within the cervix are uncommon if one excludes endometrial carcinoma, which involves the cervix by direct spread. A variety of other neoplasms rarely metastasize to the cervix and, in most cases, the diagnosis is straightforward because of a combination of clinical and pathologic parameters, common features of metastatic carcinoma within the cervix including predominant involvement of the deep stroma, absence of surface involvement and of an in situ component, and prominent lymphovascular permeation. We describe 6 cases of metastatic adenocarcinoma involving the cervix with superficial "mucosal" involvement mimicking primary cervical adenocarcinoma or adenocarcinoma in situ. In 5 cases, the primary adenocarcinoma was in the ovary or peritoneum and was of serous (4 cases) or clear-cell (1 case) type. In the other case, the primary neoplasm was in the pancreas and this was initially interpreted as a primary cervical adenocarcinoma. In the cases of primary ovarian or peritoneal carcinoma, the mucosal tumor within the cervix, which was discovered at the same time as the ovarian or peritoneal neoplasm, raised the possibility of synchronous independent lesions or metastasis from the cervix to the ovary or peritoneum. Positive staining for WT1, p53, and estrogen receptor in the cases of serous carcinoma and an absence of human papillomavirus by linear array genotyping in all cases was of value in excluding a primary cervical neoplasm, although these ancillary studies are supplementary to microscopic examination. In those cases with an ovarian or peritoneal primary, the likely pathogenesis of the cervical involvement is transtubal and intrauterine spread. It is important for the pathologist to be aware of the possibility of cervical mucosal metastasis to avoid an erroneous diagnosis of a primary cervical adenocarcinoma or adenocarcinoma in situ.

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