Merce Jorda

Analysis of thyroid transcription factor-1 and cytokeratin 20 separates merkel cell carcinoma from small cell carcinoma of lung

Merkel cell carcinoma needs to be separated from small cell carcinoma metastatic from visceral sites to skin. Pulmonary small cell carcinoma is the most common primary site of small cell carcinoma. We evaluated the immunophenotypic characteristics of 21 Merkel cell carcinomas and 33 small cell carcinomas of lung using thyroid transcription factor‐1 and cytokeratin 20. Thyroid transcription factor‐1 was 100% specific for the diagnosis of small cell carcinoma of lung associated with a diagnostic sensitivity of 85%. Cytokeratin 20 was present in 95% of Merkel cell carcinomas; however, 33% of small cell carcinoma of lung were also positive. Both antibodies typically demonstrate diffuse and intense staining of their respective tumor cells. We conclude that thyroid transcription factor‐1 is a sensitive and specific marker for small cell carcinomas of lung and that a combination of thyroid transcription factor‐1 and cytokeratin 20 is indicated to assist in the differentiation of metastatic small cell carcinoma of lung from merkel cell carcinoma.

Melan A (A103) is expressed in adrenocortical neoplasms but not in renal cell and hepatocellular carcinomas.

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.

Her2 Expression in Prostatic Cancer: A Comparison With Mammary Carcinoma

PURPOSEnThere is growing interest in HER2 and its downstream signaling pathway molecules as treatment targets in human malignancies, including prostatic carcinoma. We used a standard Food and Drug Administration approved HER2 immunohistochemical kit to study HER2 expression in prostate cancer. We compared the results with those reported for mammary carcinoma.nnnMATERIALS AND METHODSnFor this study we selected 216 specimens obtained from patients who underwent radical prostatectomy for primary untreated prostatic carcinoma. Immunohistochemical staining was performed using the HercepTest kit (Dako Corp., Carpinteria, California) in strict fashion according to the technical and analytical protocols outlined in the kit.nnnRESULTSnOf the tumors 33 (15%) were positive for HER2, including 31 (94%) that were only weakly positive (2+). Of the HER2 positive tumors 97% were Gleason grade 7 or higher. Of the 33 positive cases 22 (67%) showed only a focal positive reaction for HER2 in discrete tumor areas.nnnCONCLUSIONSnHER2 is expressed in a minority of untreated primary prostatic carcinomas. Unlike in mammary carcinoma, HER2 positivity in prostatic cancer is usually weak in intensity and focal in distribution. While the former casts doubt on the usefulness of HER2 as a potential treatment target for most primary untreated prostatic cancer, the latter phenomenon may lead to false-negative results if the test is performed in small biopsies. Furthermore, HER2 staining of prostatic carcinoma can be technically and analytically reproducible provided that there is strict adherence to the outlined methodologies and interpretation.

Gastric Endocrine Pancreatic Heterotopia

Heterotopic pancreas is a relatively infrequent lesion most often found in the stomach. Four histologic types are recognized: total, canalicular, exocrine, and endocrine heterotopia. To our knowledge, only 2 cases of purely endocrine heterotopic pancreas have been reported in detail. We describe the case of a patient with gastric and duodenal ulcers and gastric endocrine heterotopia. The lack of mass formation, histomorphology, and immunohistochemical features simulating islets of Langerhans supported the diagnosis. We conclude that purely endocrine heterotopic pancreas is a very rare entity that, when present, can simulate a primary or metastatic neuroendocrine tumor. Adequate sampling of the specimen, histomorphologic pattern, and immunohistochemistry are important for the purpose of distinguishing between a neuroendocrine tumor and purely endocrine pancreatic heterotopia.

P63 differentiates subtypes of nonsmall cell carcinomas of lung in cytologic samples: implications in treatment selection.

Bevacizumab in combination with carboplatin and paclitaxel improves overall response and survival in patients with advanced or recurrent nonsmall cell lung carcinoma. However, this drug is not recommended in patients with squamous cell carcinoma or neoplasms with a dominant squamous component. Therefore, identification of squamous cell differentiation has therapeutic implications. In many instances, cytology is the diagnostic tool of choice; however, routine cytomorphology is limited in classification of nonsmall cell carcinomas into squamous and nonsquamous subtypes. The aim of this study was to identify the value of p63 immunocytochemical analysis in this distinction.

A limited immunohistochemical panel helps differentiate small cell epithelial malignancies of the sinonasal cavity and nasopharynx.

BackgroundDistinguishing 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. DesignWe 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. ResultsAll 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. ConclusionsA 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.

Fine-Needle Aspiration Diagnosis of Angiosarcoma of the Spleen A Case Report and Review of the Literature

Primary angiosarcoma of the spleen is a very rare neoplasm with a poor prognosis. The definitive diagnosis is usually based on the histologic evaluation of the splenectomy specimen. We describe a case of angiosarcoma diagnosed by fine-needle aspiration cytology prior to splenectomy. A 69-year-old white woman presented with heterogeneous lesions in the spleen during a follow-up computed tomographic scan for a history of liposarcoma of the right buttock. A malignant endothelial neoplasm was diagnosed by fine-needle aspiration cytology using immunocytochemistry, and a splenectomy confirmed the presence of angiosarcoma. To our knowledge, this is the first well-documented and confirmed case of primary angiosarcoma of the spleen diagnosed by fine-needle aspiration cytology. This report emphasizes the value of fine-needle aspiration cytology as an important diagnostic tool in splenic neoplasms.

Low Nuclear Proliferative Activity Is Associated With Nonmetastatic Islet Cell Tumors

CONTEXTnTraditional morphologic features of tumor aggression are of limited value in predicting the malignant behavior of endocrine neoplasms. We explored the potential value of nuclear proliferative activity (using Ki-67 immunostaining with semiquantitative scoring) in predicting the clinical behavior of pancreatic islet cell tumors (ICTs), and we correlated this characteristic with hormone expression.nnnOBJECTIVEnTo evaluate whether Ki-67 immunostaining using a semiquantitative scoring system has value in predicting the clinical behavior of pancreatic ICTs.nnnDESIGNnWe studied 39 pancreatic ICTs from 39 patients. Twenty-two ICTs did not metastasize in a median follow-up period of 91 months. The remaining 17 neoplasms did produce metastases (8 in liver, 7 in regional lymph nodes, and 2 in peritoneum). Immunohistochemistry was performed using antibodies to Ki-67 and pancreatic hormones (insulin, glucagon, gastrin, somatostatin, pancreatic polypeptide, vasoactive intestinal polypeptide, and corticotropin). A semiquantitative Ki-67 grading system was followed. The nuclear proliferative activity, as determined by a positive reaction for Ki-67, was considered low (<5% of cells staining positively), intermediate (5%-25% of cells staining positively), or high (>25% of cells staining positively).nnnRESULTSnThe majority of the nonmetastatic ICTs (16 cases, 73%) demonstrated either negative or low staining for Ki-67 (P <.001). Conversely, all metastatic ICTs expressed at least an intermediate-grade reaction. High nuclear proliferative activity was only seen in metastatic neoplasms (3 cases, 17%). There was no relationship between immunoexpression of pancreatic hormones and nuclear proliferative activity by either group of tumors.nnnCONCLUSIONnAn ICT with low nuclear proliferative activity is unlikely to metastasize, whereas high proliferative activity is associated with a metastatic phenotype. Immunohistochemical assessment of Ki-67 using a semiquantitative scoring system is a simple and reliable detection method of cellular proliferative activity in ICTs of the pancreas.

High Proliferative Activity Excludes Dermatofibroma: Report of the Utility of MIB-1 in the Differential Diagnosis of Selected Fibrohistiocytic Tumors

CONTEXTnDermatofibroma is a benign fibrohistiocytic tumor composed of a mixture of fibroblastic and histiocytic cells. The diagnosis of this tumor is generally uncomplicated; however, rare variants may be difficult to distinguish from malignant fibrohistiocytic tumors. Deep penetrating dermatofibroma may be difficult to distinguish from dermatofibrosarcoma protuberans, and pseudosarcomatous dermatofibroma and dermatofibroma with monster giant cells share morphologic similarities with malignant fibrous histiocytoma and atypical fibroxanthoma.nnnOBJECTIVEnTo find an immunohistochemical marker or markers that differentiate between fibrohistiocytic lesions of skin.nnnDESIGNnWe evaluated the immunophenotypic characteristics of 83 fibrohistiocytic tumors (36 typical dermatofibromas, 16 cases of dermatofibrosarcoma protuberans, 16 malignant fibrous histiocytomas, and 15 atypical fibroxanthomas) using antibodies against MIB-1 (Ki-67), factor XIIIa, CD34 (HPCA-1), HHF35 (muscle-specific actin), 1A4 (smooth muscle actin), cytokeratin (AE1/AE3, CAM 5.2, and 34betaE12), S100 protein, and desmin.nnnRESULTSnA high proliferative index detected by MIB-1 staining excluded the possibility of dermatofibroma and was diagnostically useful in separating this entity from dermatofibrosarcoma protuberans, malignant fibrous histiocytoma, and atypical fibroxanthoma. A low proliferative index, however, could not differentiate dermatofibroma from dermatofibrosarcoma protuberans. Factor XIIIa reactivity was not helpful for the diagnosis of dermatofibroma, whereas CD34 reactivity was statistically significant in the diagnosis of dermatofibrosarcoma protuberans. The sensitivity of these 2 markers is low and therefore of questionable practical diagnostic value.nnnCONCLUSIONnEvaluation of the proliferative index may further assist in distinguishing dermatofibroma from dermatofibrosarcoma protuberans, atypical fibroxanthoma, and malignant fibrous histiocytoma.

Salivary gland-like tumors of the breast express basal-type immunohistochemical markers.

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.