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  4. Small and large cell neuroendocrine carcinomas of the uterine cervix. A report of 10 cases.
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Small and large cell neuroendocrine carcinomas of the uterine cervix. A report of 10 cases.

Journal
Virchows Archiv
Date Issued
2005-08
Author(s)
Kubelka-Sabit, Katerina
Plaseska-Karanfilska, Dijana
Prodanova, Irina
Yashar, Genghis
Hadzi-Nicheva, Biljana
Veljanoska, Slavica
Zografski, George
DOI
10.1007/s00428-005-1288-1
Abstract
BACKGROUND: Small (SCC) and large cell (LCC) neuroendocrine carcinomas of the uterine cervix are rare and highly aggressive neoplasms. Their association with the integration of human papilloma virus (HPV) DNA of the types 16 or 18 has been documented in many studies.
AIMS: The purpose of this study is to present the clinical, histopathological, immunohistochemical characteristics and the presence of HPV DNA in ten cases of SCCs and LCCs of the uterine cervix.
METHODS: Seven patients with primary SCCs and three patients with LCCs of the uterine cervix were diagnosed at our department between 1989 and 2004. Clinical data were retrieved from the patients’ files and included age, recurrence and survival. Routinely processed operative and/or biopsy specimens were used for immunohistochemical stains and hybridization procedures. Primary antibodies against several epithelial, neuroendocrine, mesenchimal and proliferative
markers were included. The presence of HPV DNA was assessed by conventional in situ hybridization (ISH) using probes for HPV 16/18 and 31/33/51 and polymerase chain reaction (PCR), using three primers (MY09/11, GP5+/GP6+, E6). Six of the patients were surgically treated. Postoperatively, four received chemo and/or radiotherapy, two rejected further treatment and one patient was lost to follow-up. The other four patients underwent conservative treatment due to advanced disease.
RESULTS: The patients’ age ranged from 25 to 71 years. Histologically, the tumors showed trabecular, nesting or a sheet-like pattern, with areas of necrosis and frequent mitoses.
Their neuroendocrine nature was confirmed by diffuse positive immunostaining for neuron-specific enolase and low-molecular weight cytokeratins. Focal positivity for chromogranin, synaptophysin and S100, together with pancytokeratin and EMA, was evident in the majority of the
tumors. Their aggressive potential was confirmed by high Ki-67 proliferative index (50-90%). HPV types 16/18 were found in 4 tumors using ISH, and HPV 16 in additional 3, using PCR (type 16). 3 of the patients developed distant metastases and died 7-48 months after receiving partial or full treatment, while 6 are alive and without evidence of disease after 4-38 months.
CONCLUSIONS: SCCs and LCCs are highly aggressive neoplasms. However, early diagnosis and combined therapy may improve survival in some patients. Although mainly a morphologic diagnosis, immunohistochemistry may help in the diagnosis of SCC and LCC.
Subjects

uterine cervix

neuroendocrine carcin...

human papillomavirus

histopathology

immunohistochemistry

In situ hybridization...

polymerase chain reac...

therapy

prognosis

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