Australian Society of CytologyCase of the Month
December 2003 - Answer and Discussion
Small cell undifferentiated carcinoma of the cervix.
Answer
Cervical Biopsy consisted of fragments of extensively necrotic tissue. Microscopically the fragments showed a poorly differentiated malignant tumour consisting of uniformly small cells with a high N/C ratio and hyperchromatic nuclei. The nuclei have a finely granular chromatin and indistinct nucleoli.
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Immunohistochemical studies were strongly +ve for low molecular weight cytokeratin and –ve for high molecular weight cytokeratin. Neuroendocrine markers including NSE were all –ve. Although the markers do not confirm the neuroendocrine character of this tumour it is still consistent with a small cell anaplastic carcinoma, a fairly high proportion of which do not show positivity for neuroendocrine markers.
Further histology of uterus, tubes and ovaries (post chemo and radiation) showed residual poorly differentiated carcinoma of the cervix and HPV effect. The vaginal wall also showed poorly differentiated carcinoma extending to the margin.
Discussion
Small cell carcinoma of the cervix (also called oat cell carcinoma) used to be regarded as a variety of squamous cell carcinoma. More recently however, there has been evidence based on immunocytochemistry and electron microscopy that this tumour is of neuroendocrine derivation.
It is thought to arise in the squamocolumnar junction of the cervix or endocervix or from endocervical neuroendocrine cells.
Small cell carcinoma is a deeply infiltrative and highly aggressive tumour with a poor prognosis (5yr survival rate is 20%) and accounts for 2-5% of tumours of the cervix. The median age of the patient is 42years and it presents as usually small, ulcerated lesions sometimes with bleeding.
It is more commonly associated with HPV 18 and less commonly with HPV 16.
Chemotherapy and radiotherapy are the preferred modality of treatment. Definitive surgery is not recommended.
Cytology:
Small Cell Carcinoma in Situ may shed many cells and these occur singly or in syncitia, with scant homogeneous cytoplasm. The nuclei are hyperchromatic, with finely stippled / coarse chromatin (S&P), sometimes molding and showing crush artifact.
The cells from a small cell CIS may be confused with endometrial cells however the latter have eccentric nuclei, finely vacuolated cytoplasm and finely granular chromatin.
The cells from Small Cell Carcinoma (Invasive) may shed in sheets or chords, in isolation or in small groups without much overlapping. There may be some molding of the nuclei. Round cells, sometimes many, are seen. They have very scant cyanophilic cytoplasm, high N/C ratio, hyperchromatic round /oval irregular nuclei with small but not prominent nucleoli.
Differential Diagnosis:
Small Cell Carcinoma sheds cells slightly larger in size than those from a well differentiated endometrial adenocarcinoma .There are no acinar structures or tight clusters as seen in the latter. The cells are slightly larger than lymphocytes however they are sometimes mistaken for such. In a case of follicular cervicitis, although the lymphocytes occur in streams, there is a mixture of lymphocytic cells and histiocytes. In small cell carcinoma there is only one population of cells. In lymphoma, cells are singular and do not show molding.
Small cell tumours are poorly differentiated and demonstrate neurosecretory argyrophillc granules which helps to differentiate them from poorly differentiated carcinoids.
Further Reading:
Meisels A and Morin C: Cytopathology of the Uterine Cervix.
Breining, Abadi, Jones: Cervical Pathology.
Vooijs G.P: Chapter 9. Comprehensive Cytopathology. Bibbo
Ng A.B.P. & Abdul-Karim F.W: Chapter 35 . Diagnostic Cytopathology. Winifred Gray.
Geisinger K et al. Modern Cytopathology.
