CD44 mediates constitutive type I receptor signaling in cervical carcinoma cells.

OBJECTIVE: The CD44 transmembrane glycoprotein family has been implicated in the growth and metastasis of numerous human cancers. CD44 may function in some cells through interactions with type I receptor tyrosine kinases, including erbB2. Here, we tested whether CD44 interacts with erbB2 and another type I receptor, the epidermal growth factor receptor (EGFR), in human cervical carcinoma tissues and cell lines and whether these interactions influence erbB2 signaling. METHODS: CD44, EGFR, and erbB2 colocalization were examined in 36 pT1b-pT2b cervical cancer cases and in the CaSki and SiHa cervical carcinoma cell lines by immunohistochemistry and laser scanning confocal microscopy. The role of CD44-EGFR-erbB2 interactions in erbB2 signaling was examined by immunoprecipitation and using antisense CD44 oligonucleotides. RESULTS: CD44, erbB2, and EGFR coexpression and colocalization were observed in 42% (15/36) of cervical carcinoma cases and in both cervical carcinoma cell lines. Colocalization occurred to an equivalent extent in all tumor grades examined. CD44 coimmunoprecipitated with erbB2 and EGFR in cervical carcinoma cell lysates, indicating that these proteins interact with each other. Reduction of CD44 expression inhibited constitutive erbB2 activity. High CD44 expression was linked to EGFR activity using dominant negative EGFR, suggesting that type I receptors may autoregulate their activity in these cells. CONCLUSIONS: Our data indicate that CD44 can mediate type I receptor function in cervical carcinoma cells that overexpress both CD44 and either erbB2 or EGFR and suggest a novel mechanism by which these proteins may contribute to cervical carcinoma tumor growth and metastasis.

Paracoccidioides brasiliensis in a postpartum Pap smear. A case report.

BACKGROUND: There are several reported cases that describe female genital tract infections with opportunistic fungi, such as Blastomyces dermatitidis, Coccidioides immitis, Aspergillus flavus, Cryptococcus neoformans and Mucor. We describe a case of paracoccidiodomycosis limited to the uterine cervix. To the best of our knowledge, no such case has been described before in the English-language literature. CASE: A 27-year-old, healthy female, gravida 3, para 2, abortion 1, presented for a routine gynecologic examination at six weeks' postpartum. Her past medical history was unremarkable. A routine cervical/endocervical smear revealed the presence of multiple fungal forms at different stages of development with a characteristic "pilot's wheel" appearance consistent with Paracoccidioides brasiliensis. Detailed medical examination of the patient did not reveal the presence of the primary infection in any other system. Cultures of the endometrium revealed no growth of the fungal organisms. The patient was asymptomatic, and therefore no therapy was initiated. Repeat Papanicolaou smears were negative for organisms. CONCLUSION: Paracoccidioidomycosis can present as a limited form, involving the cervix only. Identification and recognition of the infection are important in cytopathology.

Papillary-cystic variant of acinic cell carcinoma of the salivary gland diagnosed by fine needle aspiration biopsy. A case report.

BACKGROUND: Fine needle aspiration (FNA) biopsy is reliably used to classify most conditions involving the salivary glands. It is useful for establishing, or at least suggesting, the diagnosis in unusual cases or narrowing the differential diagnosis. CASE: A 25-year-old male presented with a slowly enlarging mass of the left parotid. FNA biopsy of the parotid gland was performed, and a diagnosis of papillary-cystic variant of acinic cell carcinoma was suggested. The patient underwent incomplete resection of the lesion, which was interpreted as acinic cell carcinoma. CONCLUSION: Papillary-cystic variant of acinic cell carcinoma is rarely seen, especially in young people. FNA biopsy is a useful diagnostic procedure that can help diagnose this relatively uncommon type of salivary gland neoplasm and guide its management.

Concomitant well-differentiated adenocarcinoma and leiomyosarcoma of the uterus.

We describe a case of a concomitant well-differentiated endometrial endometrioid adenocarcinoma and leiomyosarcoma of the uterus in a 66-year-old woman who presented with a 6-month history of vaginal bleeding. The patient underwent total hysterectomy for endometrial carcinoma diagnosed by endometrial biopsy. Gross examination of the specimen revealed an endometrial mass bulging into the endometrial cavity and an underlying well-circumscribed nodule separated from the endometrial mass by a myometrial band. Frozen section performed at the time of the total hysterectomy rendered a diagnosis of malignant mixed-müllerian tumor. Histologic examination of the permanent sections revealed well-differentiated endometrial endometrioid adenocarcinoma clearly separated from a high-grade leiomyosarcoma. Differential diagnosis included malignant mixed-müllerian tumor. However, no admixture of carcinomatous and sarcomatous elements was present. There were no heterologous elements. To the best of our knowledge, no similar case has been described in the English literature.

Metastatic female adnexal tumor of probable Wolffian origin: a case report and review of the literature.

Female adnexal tumor of probable wolffian origin is a rare neoplasm that can present diagnostic difficulties. We report herein a case of a 60-year-old woman with female adnexal tumor of probable wolffian origin arising within the leaves of a broad ligament and, 5 years later, presenting with metastasis to the liver. The morphologic, immunohistochemical, ultrastructural, and DNA ploidy findings of the original and metastatic tumor, differential diagnoses, and the results of the English-language literature review are presented.

Multilobated large B-cell lymphoma diagnosed cytologically. A case report.

BACKGROUND: Fine needle aspiration (FNA) biopsy can be used to reliably classify most conditions involving lymph nodes or, at least, significantly reduce the differential diagnosis. CASE: A 70-year-old male presented with an ulcerated mass arising from the left tonsillar fossa and involving the anterior and posterior pillars. A biopsy of the tonsillar mass performed at an outside hospital was interpreted as a large cell undifferentiated carcinoma. Subsequently the patient developed systemic lymphadenopathy. A bone scan showed intense uptake within the medial tibial plateau of the left knee. FNA biopsy of the right axillary mass was interpreted at University of Cincinnati Medical College as a large cell lymphoma, multilobated type. Histologic and immunohistochemical studies of the lymph node confirmed the presence of multilobated B-cell lymphoma. Lymphoma chemotherapy was initially successful but was discontinued due to toxicity. The patient died two months after the initial cytologic diagnosis of lymphoma. CONCLUSION: Multilobated lymphomas are an unusual variant of non-Hodgkin's lymphomas (mostly B-cell type). Cytology and immunocytochemistry are useful diagnostic procedures that can help to diagnose this relatively uncommon type of lymphoma and significantly reduce the possibility of misdiagnosis.

Amplification and expression of the cyclin D1 gene in anal and esophageal squamous cell carcinomas.

Cyclin D1 is a cell-cycle regulator and candidate proto-oncogene implicated in the pathogenesis of numerous tumor types. Amplification of the cyclin D1 gene occurs commonly in esophageal squamous cell carcinomas. However, no studies have examined the role of cyclin D1 in anal carcinogenesis. We examined 20 esophageal squamous cell carcinomas and 24 anal carcinomas for cyclin D1 alterations. Protein expression was evaluated by immunohistochemistry using the cyclin DIGM antibody (Novocastra, Newcastle upon Tyne, UK). Cyclin D1 amplification was examined by fluorescent in situ hybridization (FISH), using a cyclin D1 probe obtained from Toshiya Inaba at St. Jude Children's Research Hospital, Memphis, TN. The FISH sections were analyzed using a Leica (Deerfield, IL) confocal microscope. By immunohistochemistry, 75% of esophageal carcinomas showed evidence of cyclin D1 expression. Cyclin D1 amplification was detected by FISH in 65% of esophageal cancers. There was good correlation between cyclin D1 protein expression and gene amplification, although some tumors showed protein overexpression in the absence of gene amplification. Among the 24 anal carcinomas studied, 8% showed weak cyclin D1 immunoreactivity in rare tumor cells. None of the anal tumors showed cyclin D1 amplification. We conclude that cyclin D1 alterations are common in esophageal carcinomas but do not appear to be important in anal carcinogenesis. Immunohistochemical detection of cyclin D1 protein overexpression is a good predictor of cyclin D1 amplification.