Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an underrecognized low-grade carcinoma with predilection to the eyelid. Only 4 cases of this entity have been described in the literature. Here, we describe 12 cases of EMPSGC. The lesions were twice as frequent in females than males with an average age of 70 years (range, 48-84 years). Clinically, they presented as a slowly growing cyst or swelling. The most common site of occurrence was the lower eyelid (8 cases). Two lesions occurred on the upper eyelid and 2 on the cheek. Histologically, they were well-circumscribed, typically multinodular tumors with solid or partially cystic nodules, frequently showing areas of papillary architecture. Focal cribriform arrangements were also present. The nodules were formed by uniform small- to medium-sized oval to polygonal epithelial cells with lightly eosinophilic to bluish cytoplasm. The nuclei were bland with diffusely stippled chromatin and inconspicuous nucleoli. Intracytoplasmic and extracellular mucin was usually present. Mitotic activity was present but never brisk. All tumors examined immunohistochemically expressed at least one neuroendocrine marker, synaptophysin or chromogranin. CD57 and neuron specific enolase, secondary markers of neuroendocrine differentiation, were expressed in most cases. All tumors tested expressed estrogen and progesterone receptors, cytokeratin 7, low molecular cytokeratin Cam5.2, and epithelial membrane antigen and were negative for cytokeratin 20 and S-100 protein. Calponin, smooth muscle actin, and p63 immunohistochemical stains did not disclose myoepithelial cells around larger tumor nests in most cases, supporting the notion that EMPSGC is an invasive carcinoma. In 10 cases, cystic areas lined by benign epithelium indistinguishable from eccrine ducts were present. In some foci, the benign ductal epithelium was undermined or replaced by carcinoma in situ with similar cytologic features to the solid or papillary areas of EMPSGC. Myoepithelial cells were preserved in the areas of in situ carcinoma. In 6 cases, EMPSGC was associated with invasive mucinous carcinoma. In situ carcinoma and mucinous carcinoma also expressed neuroendocrine markers. Clinical follow-up showed no recurrences or metastases, consistent with low-grade carcinoma. The series provides histologic evidence for a multistage progression of noninvasive sweat gland neuroendocrine carcinoma to EMPSGC and then to mucinous carcinoma of the eyelid. Although the data from this series support the notion that the prognosis of EMPSGC and mucinous carcinoma is good, longer follow-up is needed for better understanding of their pathogenesis and clinical behavior.

Context.—The complexities of diagnostic hematopathology in the modern era are well known, and even in this molecular era, immunophenotypic studies, together with routine histopathology, remain a critical component in the evaluation of many lymphoid proliferations. With numerous antibodies that can be used on routinely fixed, paraffin-embedded tissue sections, immunohistochemistry has become increasingly valuable. It then becomes a challenge knowing the best approach to the selection of antibodies to use and how to interpret them. Objective.—To present a pragmatic immunohistochemical approach to the evaluation of lymphoid proliferations that stresses the utility of 2 limited panels to deal with the most commonly encountered lymphomas. Data Sources.—English-language literature published between 1990 and 2008. Conclusions.—A relatively limited panel of immunohistochemical stains may be used to diagnose and subclassify many of the more common lymphomas, although some cases will require additional stains and others fewer, depending on the case complexity. Immunohistochemical stains must always be interpreted in the context of the histopathologic and other ancillary studies.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is common in the Western world. Genetic abnormalities detected by fluorescence in situ hybridization (FISH) and immunoglobulin heavy chain variable gene region (IGHV) mutational status are well-known independent prognostic indicators in CLL/SLL. Given the requirement for specialized testing to detect such aberrations, we investigated whether morphologic features may predict the presence of a more or less favorable genetic profile. Forty-one SLL cases were morphologically evaluated for expanded proliferation centers, increased large cells outside of proliferation centers, and nuclear contour irregularities (NCI) in small and large tumor cells. ZAP-70 immunohistochemistry and FISH (deletions of 13q14, p53 and ATM and trisomy 12) were successful in all cases. IGHV mutational status was determined in 26/41 cases. Significant NCI in both small and large cells correlated with the presence of an unfavorable FISH abnormality (ie, ATM or p53 deletions). However, despite good specificity (94%), the sensitivity (57%) of this finding is inadequate for routine use. No other significant associations with morphologic features were identified. Strong ZAP-70 positivity correlated with unmutated IGHV (P=0.001), rendering ZAP-70 IHC a useful surrogate for IGHV mutational status. ZAP-70 positivity predicted against finding a favorable FISH deletion 13q14 (P=0.023). Although we only studied 41 cases, we corroborated their validity using Kaplan-Meier overall survival analysis. In conclusion, morphologic features in SLL are not a reliable predictor of underlying genetic status. Thus, we propose a practical, cost-effective approach to the work-up of these cases, which should be driven by clinical necessity.