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3.c.iii Small Cell Carcinoma

Small Cell Carcinoma
Small Cell Carcinoma
Small Cell Carcinoma

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Small cell carcinoma (SmCC) of the cervix is a rare poorly differentiated neuroendocrine tumor which shares many similarities with SmCC of the lung. They have a similar histology, they can be associated with paraneoplastic syndrome, their main treatment modality is chemotherapy and radiation therapy and their outcome remains poor with a high rate of early distant metastases and low survival rate at 1 year. SmCC of the cervix has been shown to be HPV induced (see reference).

On histology, SmCC is composed of small blue cells with high nuclear-cytoplasmic ratio, scant cytoplasm and markedly atypical hyperchromatic nuclei with finely stippled chromatin. Nuclear molding is typically present and nucleoli are inconspicuous. SmCC has a high proliferation rate; mitotic activity is plentiful (>10 mitoses / 10HPFs) and there is conspicuous apoptosis as well as necrosis. The architectural pattern may vary, including sheet-like, insular or spindled cells architecture. Some acinar formations may also be seen. The diagnosis is confirmed with immunohistochemical staining: SmCC should be positive for at least one neuroendocrine marker (synaptophysin, chromogranin, CD56) and has a characteristic dot-like cytoplasmic staining with low molecular weight cytokeratin.

The main differential diagnoses include poorly differentiated squamous cell carcinoma (SCC) or poorly differentiated adenocarcinoma and pathologists should be aware that SmCC often develops concomitantly with a usual SCC or adenocarcinoma. The presence of the characteristic nuclear features of SmCC as well as its immunophenotype usually allows establishing the diagnosis. A diagnosis of non-Hodgkin lymphoma should also be considered and excluded with an immunohistochemical study.

The main challenge remains to establish the diagnosis on a small cervical biopsy which often shows crush artefacts, tissue fragmentation and streaming effect. Also, it is more advisable to render a diagnosis of "poorly differentiated carcinoma with neuroendocrine features" on a small biopsy specimen in order not to deprive early stage patients from being treated surgically since SmCC could only be a minor component within an otherwise conventional cervical carcinoma.

Reference:
Nofech-Mozes S, Khalifa MM, Ismiil N, Dubé V, Saad RS, Sun P, Seth A, Ghorab Z. Detection of HPV-DNA by a PCR-based method in formalin-fixed, paraffin-embedded tissue from rare endocervical carcinoma types. Appl Immunohistochem Mol Morphol. 2010 Jan;18(1):80-5. PMID: 19625948.

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