Cytologic diagnosis of atypical squamous cells of undetermined significance in perimenopausal and postmenopausal women: lessons learned from human Papillomavirus DNA testing.

BACKGROUND: The authors have noted that in cervical cytology specimens from perimenopausal and postmenopausal women, the diagnosis of atypical squamous cells of undetermined significance (ASC-US), as defined in the Bethesda system, is often not associated with a clinically evident lesion on follow-up. Reflex human papillomavirus (HPV) testing provides an opportunity to distinguish cytologic features of significance from those within the spectrum of benign cellular change in this age group. METHODS: Liquid-based preparations that were diagnosed as ASC-US between January 2003 and July 2005 at Emory University Hospital were identified from the computer files. The results of HPV-DNA testing were recorded. Two hundred four Papanicolaou tests from perimenopausal women (n = 81, 40-49 years) and postmenopausal women (n = 123, >50 years) were reviewed in a blinded fashion. RESULTS: HPV-DNA results were available for 903 of 1044 patients diagnosed as ASC-US. Overall, 323 results (35.8%) were positive, 510 results (56.6%) were negative, and 70 results (7.8%) were indeterminate. In addition, 73% of ASC-US specimens in patients aged > or =40 years were negative for HPV DNA. The HPV-DNA detection rate dropped from 60% in the group ages 10 to 19 years to approximately 18% in the group aged >50 years. A review of HPV-negative cases in the group aged >40 years showed squamous cells with random nuclear enlargement and slight hyperchromasia that likely were interpreted as ASC-US (based on the cells that were dotted by the original reviewer). Nuclear grooves were frequent in these nuclei; and cytoplasmic halos, when present, usually were perinuclear. CONCLUSIONS: HPV-DNA detection in cervical cytology specimens has an inverse relation to patient age. A diagnosis of ASC-US in perimenopausal and postmenopausal women is likely to result in a negative HPV-DNA test in a significant proportion of patients. Enlarged nuclei with nuclear grooves and slight hyperchromasia are possibly the cause of ASC-US overdiagnosis in this age group.

Fine-needle aspiration cytologic diagnosis of metastatic melanotic schwannoma: familial case of a mother and daughter with Carney's complex and literature review.

Carney's complex is an autosomal dominant, multisystem tumorous disorder that includes myxomas, spotty skin pigmentation, endocrine tumors, and peripheral nerve tumors. Psammomatous melanotic schwannomas have recently been included as a part of this complex. Here, we describe the first known familial case of a mother and daughter, both presenting with malignant, already metastatic, pigmented schwannomas initially diagnosed as metastatic melanoma by CT guided fine-needle aspiration. Patients with highly pigmented, extra-cutaneous lesions that are clinically and pathologically suspicious for metastatic malignant melanoma, without known primary tumor, should be evaluated for possible Carney's complex. Additional screening of family members should be recommended to exclude the presence of potentially malignant neoplasms, such as psammomatous melanotic schwannomas.

Rapid intraoperative immunohistochemical evaluation of sentinel lymph nodes for metastatic breast carcinoma.

OBJECTIVE: Sentinel lymph node (SLN) biopsy is an integral part of the surgical management of patients with breast cancer. Rapid immunohistochemistry (RIHC) has the potential to increase detection of metastatic carcinoma at the time of frozen section consultation. The authors assessed the accuracy and turnaround time of a newly developed RIHC method for pancytokeratin (RIHC-CK). METHODS: Sixty-six SLNs from 32 patients with breast carcinoma were examined for metastasis using the Zymed Sentinel Lymph Node Rapid IHC Kit. Intraoperative frozen sections (6 mum) of the SLNs were incubated with Zymed anti-pan-cytokeratin/HRP conjugate, diaminobenzidine (DAB), and stained with hematoxylin. Slides were ready within 8 minutes and were interpreted as positive or negative for metastatic carcinoma. Results were compared with previous intraoperative touch preparations, frozen sections, hematoxylin and eosin (Perm H&E), and AEl/3-immunostained permanent sections (Perm CK). RESULTS: Fourteen lymph nodes (19%) in 13 patients tested positive for metastatic carcinoma in Perm H&E, the gold standard. RIHC-CK had the highest sensitivity (92%) of the intraoperative tests, compared with touch preparations (64%) and frozen sections (80%). RIHC-CK showed 94% accuracy, compared with 96% (frozen section) and 93% (touch preparation). The RIHC technique took 8 minutes and was easy to perform and interpret. CONCLUSIONS: Zymed RIHC is a sensitive method for detecting breast cancer metastases in SLNs. The speed, accuracy, and ease of interpretation of the test allow for recognition of micrometastases (<2 mm) that might otherwise be undetectable by current methods of intraoperative evaluation. The prognostic significance and effect on surgical management of micrometastases in SLNs have yet to be determined.