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Background: Salivary gland-like tumors represent approximately 2% of primary breast carcinomas. These special histologic subtypes are characteristically negative for ER, PR, and HER2 (triple negative), and include adenoid cystic carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, and polymorphous low-grade adenocarcinoma. Approximately 75% of triple-negative breast carcinomas belong to the basal-like subtype by gene expression profiling. Immunohistochemical panels that include basal-like markers such as EGFR, CK5/6, p-cadherin, p63, and c-kit provide useful surrogates to gene expression arrays for classification of triple-negative breast cancers into the basal-like subtype. The purpose of this study was to explore the expression of these markers in salivary gland-like tumors of the breast., Design: Excisional specimens from 10 untreated invasive triple-negative mammary carcinomas with salivary gland-like morphologies were evaluated for the immunohistochemical expression of EGFR, CK5/6, p-cadherin, p63, and c-kit using formalin-fixed, paraffin-embedded tissue and the L-SAB detection method., Results: On the basis of morphology, 5 carcinomas were classified as adenoid cystic, 3 as mucoepidermoid, and 2 as polymorphous low grade. All of the adenoid cystic carcinomas, mucoepidermoid carcinomas, and polymorphous low-grade adenocarcinomas showed strong and diffuse expression of CK5/6, p-cadherin, and p63. EGFR was expressed weakly in adenoid cystic carcinomas and polymorphous low grade, whereas mucoepidermoid carcinomas had a stronger expression. C-kit was expressed in adenoid cystic carcinomas and low-grade polymorphous, but only weakly positive in mucoepidermoid carcinomas., Conclusions: Adenoid cystic, mucoepidermoid, and polymorphous low-grade carcinomas of the breast express immunohistochemical markers that characterize the intrinsic basal-like subtype of breast cancer.

Background: The distinction between renal cell carcinoma conventional (clear cell) type with eosinophilic morphology (ccRCC), chromophobe renal cell carcinoma eosinophilic variant (chRCC), and renal oncocytoma (RO) is a common diagnostic dilemma. We aimed to identify an immunohistochemical panel to discriminate ccRCC from its morphologic mimics., Materials and Methods: Fifty-three renal neoplasms (19 ccRCC, 18 chRCC, and 16 RO) were selected. Immunohistochemical stains for CD10, cytokeratin 7 (CK7), c-Kit, E-cadherin, N-cadherin, kidney-specific cadherin (Ksp-cadherin), and Recepteur d'origine nantais (RON) were performed., Results: Ten (53%) of 19 ccRCC were positive for CD10, 11 (58%) for E-cadherin, 8 (42%) for N-cadherin, 5 (26%) for Ksp-cadherin, 9 (47%) for RON, 6 (32%) for CK7, and 5 (26%) for c-Kit. In chRCC/RO group, 5 of 34 (15%) were positive for CD10, 32 (94%) for E-cadherin, 2 (6%) for N-cadherin, 1 (3%) for Ksp-cadherin, 22 (65%) for RON, 14 (41%) for CK7, and 25 (25/32, 76%) for c-kit. Univariately, negative c-Kit [odds ratio (OR)=8.75, P=0.001, area under the receiver operating characteristic curve (AUC)=0.747], negative E-cadherin (OR=11.64, P=0.005, AUC=0.681), positive N-cadherin (OR=11.64, P=0.005, AUC=0.681), positive Ksp-cadherin (OR=11.79, P=0.031, AUC=0.617), and positive CD10 (OR=6.44, P=0.005, AUC=0.690) detects ccRCC versus chRCC/RO. Multivariate analysis showed significant association between CD10 positivity and ccRCC (OR=16.90, P=0.007) and between RON negativity and ccRCC (OR=7.17, P=0.047) when CK7 is negative., Conclusions: The best single predictors for ccRCC are negative c-Kit, negative E-cadherin, positive N-cadherin, positive Ksp-cadherin, and positive CD10. However, considering the studied markers, a combination of positive CD10 and negative CK7 and RON is considered the best immunohistochemical panel in distinguishing ccRCC from chRCC/RO.

Context: High-grade neuroendocrine carcinomas and small cell carcinomas (HGNEC/SmCC) of the urinary bladder are uncommon but aggressive neoplasms. Differentiation of HGNEC/SmCC from high-grade urothelial carcinoma (UC) is based on histomorphologic features, but can be difficult in small biopsies and cases with mixed morphology., Objective: We attempt to identify a limited immunohistochemical panel that aids in this distinction., Design: We selected 39 cases of bladder carcinoma with small cell morphology: 7 HGNEC/SmCC, 21 high-grade UC with neuroendocrine-like pattern, and 11 mixed neoplasms. Immunohistochemistry for pan-cytokeratin, synaptophysin, chromogranin, p63, and thyroid transcription factor-1 was performed., Results: Pan-cytokeratin was positive in 6 of 7 cases (86%) of the HGNEC/SmCC group. All 7 tumors were positive for synaptophysin, 6 of them were negative for p63 and chromogranin, and 1 was positive for p63 and chromogranin. All 21 high-grade UC with neuroendocrine-like pattern of growth showed positive staining for pan-cytokeratin, and were all negative for synaptophysin and chromogranin. Sixteen (76%) of high-grade UC were also positive for p63. All 11 mixed tumors were positive for pan-cytokeratin. In 10 of the 11 mixed tumors (91%), synaptophysin was positive in the neuroendocrine differentiated areas and it was negative in the urothelial component. In 2 of the 11 mixed tumors (18%) chromogranin was also positive. Three (27%) of the 11 mixed cases were positive for p63 in the UC foci. Chromogranin was negative in 6 of the pure HGNEC/SmCC and in 8 of the mixed tumors. None of the 39 samples were reactive for thyroid transcription factor-1., Conclusions: A limited immunohistochemical panel including pan-cytokeratin, synaptophysin, and p63 discriminates HGNEC/SmCC from high-grade UC.

Context/objective: p16 is a widely used immunohistochemical marker in gynecologic pathology. Strong and diffuse cytoplasmic and nuclear expression of p16 in squamous cell carcinomas (SCC) of the female genital tract is strongly associated with high-risk human papilloma virus infection and neoplasms of cervical origin. However, p16 can be expressed in other neoplasms and in several normal human tissues. Occasionally, SCCs may involve both uterine cervix and urinary bladder. Accurate identification of the site of origin in such cases has therapeutic and prognostic implications. We investigate the potential value of p16 expression in this distinction., Design: We reviewed 74 SCCs, 38 (51%) from urinary bladder and 36 (49%) from uterine cervix obtained between 2003 and 2008. Of the 38 cases of bladder carcinoma, 21 occurred in females and 17 in males. Immunohistochemical analysis for p16 (DAKO M7247, clone 484, dilution of 1:50) expression was done in all cases using the labeled streptavidin-biotin method., Result: Strong and diffuse nuclear and cytoplasmic p16 positivity was observed in 45 cases (61%). Of the 38 SCCs of urinary bladder, 14 (37%) expressed p16 (8 males, 6 females). Of the 36 SCCs of uterine cervix, 31 (86%) were positive for p16., Conclusions: (1) The majority of SCCs of uterine cervix express p16. (2) More than a third of urinary bladder SCCs express p16. (3) SCCs of urinary bladder express p16 independent of gender. (4) p16 immunohistochemical expression alone cannot be used to discriminate between SCCs arising from uterine cervix versus urinary bladder.

Background: Distinguishing small cell epithelial malignancies of the sinonasal cavity and nasopharynx is difficult due to overlapping morphologic characteristics, particularly in small biopsies. This distinction is important, however, because of the inherent differences in biology, natural history, prognosis, and treatment among these neoplasms. The aim of this study is to identify a limited immunohistochemical panel that may help to differentiate these morphologically similar small cell epithelial malignancies., Design: We reviewed 37 cases of histologically similar small cell epithelial malignancies of the sinonasal cavity and nasopharynx: nasopharyngeal carcinoma (NPC) (16), basaloid squamous cell carcinoma (BSCC) (15), and high-grade neuroendocrine carcinoma (HGNEC) (6) obtained at Jackson Memorial Hospital/UM Sylvester Comprehensive Cancer Center between 2003 and 2007. Immunohistochemistry for pancytokeratin (CK), CK5/6, p63, and HLA-DR was performed using the labeled streptavidin-biotin method., Results: All cases in this study were positive for CK and p63. The CK staining pattern of HGNEC was characteristically dot-like whereas the remaining tumors stained with strong and diffuse cytoplasmic membrane positivity. Likewise, the p63 staining pattern of HGNEC was focal and weak whereas the remaining tumors stained with diffuse and strong nuclear positivity. Immunohistochemistry for HLA-DR was positive in all cases of NPC, whereas BSCC and HGNEC were uniformly negative. Cases of NPC and BSCC were positive for CK5/6 whereas cases of HGNEC were negative., Conclusions: A limited immunohistochemical panel of CK, CK5/6, p63, and HLA-DR is useful in discriminating nasopharyngeal, basaloid squamous cell, and high-grade neuroendocrine carcinomas of the sinonasal cavity and nasopharynx.

Most adrenocortical neoplasms, renal cell carcinomas, and hepatocellular carcinomas are diagnosed by a combination of clinical and morphologic features. However, occasionally this histologic differential diagnosis requires additional ancillary tests, such as immunohistochemistry. The authors investigated the potential value of A103 in the differential diagnosis of these tumors. Thirty-two adrenocortical neoplasms, 86 renal cell carcinomas, and 57 hepatocellular carcinomas were evaluated by immunohistochemistry using a monoclonal antibody A103 and a standard ABC method. The adrenocortical neoplasms were 21 adenomas and 11 carcinomas. Thirty-one of the 32 adrenocortical neoplasms showed strong and diffuse granular cytoplasmic staining for Melan A. No nuclear reaction was observed. There were no differences in staining patterns between adrenocortical adenomas and carcinomas. With the exception of one clear cell renal cell carcinoma, all non-adrenocortical neoplasms were negative. The authors conclude that A103 is a useful addition to the immunohistochemical panel in the differential diagnosis of adrenocortical neoplasms from both renal cell and hepatocellular carcinomas. This marker, however, does not separate benign from malignant adrenocortical neoplasms.

Most adrenocortical neoplasms and pheochromocytomas can be diagnosed by a combination of clinical findings and morphologic features. Occasionally, however, this histologic differential diagnosis requires ancillary tests, such as immunohistochemistry. Both tumors are generally negative for epithelial markers but express synaptophysin. Inhibin and chromogranin are used for the diagnosis of adrenocortical neoplasms and pheochromocytomas, respectively. Both antigens, however, are expressed focally and may be completely negative, particularly in small biopsies. The authors investigated the potential value of adding calretinin to inhibin in the differential diagnosis of these tumors. Fifty-five primary adrenal neoplasms including 33 adrenocortical tumors (21 adenomas and 12 carcinomas), 22 pheochromocytomas, and 7 healthy adrenal glands were examined immunohistochemically for the expression of calretinin and inhibin. Inhibin was demonstrated in 24 (73%) adrenocortical neoplasms. When calretinin was added, the number of tumors staining positively for the two markers alone or in combination increased to 31 (94%). Both antigens showed a focal pattern of distribution in many cases. None of the pheochromocytomas reacted for any of these two markers. Healthy adrenal gland showed a distinct positive and negative pattern of immunoreactivity for both antigens in cortex and medulla, respectively. There were no differences between staining patterns of calretinin and inhibin in healthy adrenal cortex, adrenocortical adenomas, and adrenocortical carcinomas. The authors conclude that the addition of calretinin to inhibin increases the sensitivity of the diagnosis of adrenocortical neoplasms. When used together, they are highly specific and sensitive for the differential diagnosis of these tumors from pheochromocytomas. These markers, however, do not distinguish between benign and malignant adrenocortical neoplasms.