Role of mitoses in cervical squamous epithelium in grading of dysplasia

Cervical intraepithelial neoplasia is a premalignant (dysplastic) lesion characterized by abnormal cellular proliferation, maturation, and nuclear atypia. The intraepithelial distribution, density, and nature (typical or atypical) of mitotic figures are used routinely to grade dysplasia and distinguish high-grade dysplasia from potential histologic mimics, such as transitional metaplasia, atrophy, or immature squamous metaplasia. The ­authors conducted a study to evaluate the total mitotic indices of the cervical epithelia in hysterectomy specimens from ­patients with and without dysplastic lesions. They also investigated a possible relationship between mitotic index and hormonal status using the endometrial maturation phase as a surrogate indicator of the latter. The authors analyzed 274 cervices from hysterectomy specimens (135 cases without dysplasia and 33, 35, and 71 cases with grades 1, 2, and 3 cervical intraepithelial neoplasia, respectively). They determined cervical mitotic index (total mitotic figures per 10 high-power fields in the most proliferative area) for each case. The endometrium in each case was classified as atrophic, early proliferative, late proliferative, and ­secretory. For all three dysplasia grades, cases in the proliferative endometrium group always had a higher average mitotic index than those in the secretory and atrophic endometrium groups; this observation also held true for the benign cases. Furthermore, the average mitotic index in all three dysplasia grades was ­always lowest in the atrophic endome­trium group. Although the mitotic index showed expected patterns of increases with increasing dysplasia grades for most of the endometrial phases, this was not a universal finding. Notably, the average mitotic index for the cervical intraepithelial neoplasia 1 cases with late proliferative endometrium was higher than for cervical intraepithelial neoplasia 2 cases with secretory and atrophic endometrium. The authors concluded that hormonal status, as reflected in endometrial maturation, can significantly affect the mitotic index of dysplastic squamous epithelium of the uterine cervix. These findings confirm that the pathologic grading of dysplasia, especially in equivocal cases such as metaplastic squamous epithelium, should not be solely dependent on finding mitoses in the cervical squamous epithelium. The full composite of histopathologic features should form the basis for this determination.

Fadare O, Yi X, Liang SX, et al. Variations of mitotic index in normal and dysplastic squamous epithelium of the uterine cervix as a function of endometrial maturation. Mod Pathol. 2007; 20: 1000- 1008.

Reprints: Dr. W. Zheng, Dept. of Pathology, University of Arizona College of Medicine, 1501 N. Campbell Ave., #5224A, Tucson, AZ 85724; zhengw@email.arizona.edu.

Detection of CD23 expression in cutaneous nonlymphoid neoplasms

Cluster designation 23 is generally used as a lymphoid marker. Its utility in cutaneous epithelial tumors has never been studied. The authors ­observed in their practice that CD23 reacted strongly with eccrine and apocrine secretory coils. Conse­quently, they performed immunohistochemical staining of CD23 in 131 cases of apocrine, eccrine, follicular, and other cutaneous nonlymphoid tumors. The authors detected CD23 expression in all benign apocrine tumors and half of benign eccrine tumors, particularly those derived from secretory coils. CD23 staining was seen in 42 percent (eight of 19) of microcystic adnexal carcinomas (MACs), while no staining was observed in tumor cells of desmoplastic trichoepithelioma, morpheaform basal cell carcinoma, and syringoma. All mammary and extramammary Paget's ­disease was labeled with CD23. In comparison, pagetoid Bowen's disease, melanoma in situ, and sebaceous carcinoma exhibited negative staining. In addition, CD23 reacted diffusely with cutaneous mucinous eccrine carcinoma in a manner similar to breast or colonic adenocarcinoma. The authors concluded that CD23 appears to be a reliable immunohistochemical marker of the eccrine/apocrine secretory coil and helpful in identifying sweat gland tumors of such origin. It is of ancillary value in differentiating MAC from its mimicker. CD23 is a useful addition to the diagnostic immunohistochemical panels for Paget's disease.

Carvalho J, Fullen D, Lowe L, et al. The expression of CD23 in cutaneous non-lymphoid neoplasms. J Cutan Pathol. 2007; 34; 693- 698.

Reprints: Linglei Ma, Dept. of Pathology, Dermatopathology Division, University of Michigan, M3260, Medical Sciences 1, 1301 Catherine Rd., Ann Arbor, MI 48109-0602; lingleim@umich.edu

Isolated HMB45 and Melan A-positive cells in melanoma sentinel lymph nodes

The use of immunohistochemistry with melanocytic markers, such as HMB45 and Melan A, increases the detection rate for micrometastases, but some cases have isolated immunohistochemically positive cells (IPC). The authors conducted a study to determine the prognostic significance of isolated HMB45 or Melan A-positive cells, or both, in melanoma sentinel lymph nodes (SLNs). They compared the clinical course of 47 patients with IPC to 308 patients with negative SLN and 122 patients with micrometastases. The mean followup for the study was 38.1 months. By Kaplan-Meier analyses, the relapse-free and overall survival rates of patients with IPC were similar to those for SLN-negative patients. Patients with micrometastases had significantly worse relapse-free and overall survival rates. In the 47 patients with IPC, six relapses (12.8%) and three melanoma-related deaths (6.4%) occurred. In the SLN-negative patients, there were 36 relapses (11.7%) and 17 melanoma-related deaths (5.5%). And in the patients with micrometastases, there were 46 relapses (37.7%) and 29 melanoma-related deaths (23.8%). The authors found that the prognosis for patients with IPC in SLN did not correlate with the type of positive staining (HMB45, Melan A, or both), capsular involvement, number of cells, presence of cytologic atypias of IPC, or tumor penetrative depth. The authors concluded that, with short-term followup, IPC in melanoma SLN is of no prognostic significance.

Satzger I, Völker B, Meier A, et al. Prognostic significance of isolated HMB45 or Melan A positive cells in melanoma sentinel lymph nodes. Am J Surg Pathol. 2007;31(8):1175-1180.

Reprints: Dr. Imke Satzger, Dept. of Dermatology and Allergology, Hannover Medical School, Ricklinger Str. 5, D-30449 Hannover, Germany; satzger.imke@mh-hannover.de

Necrotizing sialometaplasia versus invasive carcinoma of the head and neck

The authors conducted a study to investigate the use of immunohistochemistry in distinguishing necrotizing sialometaplasia from squamous cell and mucoepidermoid carcinomas by identifying myoepithelial cells and cytokeratin expression. They examined 13 cases with the histological changes of necrotizing sialometaplasia, eight squamous cell carcinomas, and eight mucoepidermoid carcinomas with the immunohistochemical markers calponin, S100, smooth muscle actin, p63, CK7, CK5, CK6, and CAM5.2. They recorded the distribution and intensity of staining. Residual myoepithelial cells, best demonstrated by calponin and smooth muscle actin, were identified at the periphery of the epithelial islands in all cases of necrotizing sialometaplasia (although not in all islands), in contrast to mucoepidermoid and squamous cell carcinomas. S100 showed a similar pattern, although staining fewer cells. Moderate rather than extensive expression of CK7 may help to distinguish necrotizing sialometaplasia from mucoepidermoid carcinoma. The authors concluded that identifying myoepithelial cells and CK7 expression may help to distinguish necrotizing sialometaplasia from its mimics.

Rizkalla H, Toner M. Necrotizing sialometaplasia versus invasive carcinoma of the head and neck: the use of myoepithelial markers and keratin subtypes as an adjunct to diagnosis. Histopathology. 2007;51(2):184-189.

Reprints: Dr. Mary Toner at mtoner@tcd.ie

Parathyroid carcinoma, atypical parathyroid adenoma, or parathyromatosis?

Parathyroid carcinoma, atypical parathyroid adenoma, and parathyromatosis can be differentiated relatively easily from typical parathyroid adenomas, but distinguishing them from each other is more difficult. Consequently, the authors performed a retrospective study of 28 consecutive patients with parathyroid carcinoma, seven patients with atypical parathyroid adenoma, and 13 patients with parathyromatosis. All were treated at the University of California at San Francisco Medical Center between 1966 and 2005. They compared for the three groups patient demographics and clinical characteristics, indications for surgery, intraoperative findings, histopathologic characteristics, disease recurrence or persistence, sites of invasion/metastases, and survival rates. The authors found that para­thyroid carcinoma (19 of 28 patients) and atypical adenoma (four of seven patients) were significantly more common in men, whereas parathyromatosis was more common in women (10 of 13 patients; P=0.02). A palpable neck mass and hoarseness were almost exclusively present in patients with parathyroid carcinoma. Prior to the first parathyroid surgery, patients with parathyroid carcinoma were found to have higher blood calcium levels (14 mg/dL or more in 16 of 26 patients [62%]), whereas only one of six patients with atypical adenoma (17%) and no patients with parathyromatosis were found to have profound hypercalcemia (P<0.01). Intraoperatively, patients with parathyroid carcinoma and atypical adenoma presented with single lesions, whereas patients with parathyromatosis had multiple small lesions. Histopathologic findings were well defined in parathyroid carcinoma, but some findings overlapped in the three tumors studied. The authors concluded that patients with parathyroid carcinoma often differ from those with atypical parathyroid adenoma or parathyromatosis at the time of presentation because those with parathyroid carcinoma have more profound hypercalcemia and invasive tumors. However, it can be difficult to distinguish between these conditions clinically and by final histologic examination.

Fernandez-Ranvier GG, Khanafshar E, Jensen K, et al. Parathyroid carcinoma, atypical parathyroid adenoma, or parathyromatosis? Cancer. 2007;110:255-264.

Reprints: Dr. Orlo H. Clark, Dept. of Surgery, UCSF/Mt. Zion Medical Center, University of California at San Francisco School of Medicine, 1600 Divisadero St., San Francisco, CA 94143-1674; clarko@surgery.ucsf.edu

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