p40 (ΔNp63) is more specific than p63 and cytokeratin 5 in identifying squamous cell carcinoma of bronchopulmonary origin: a review and comparative analysis.

The therapeutic options now available for pulmonary squamous cell carcinoma (SQCC) and adenocarcinoma (ADC) are very different. The increasing demand to make a diagnosis on minimal tissue, ancillary techniques such as immunohistochemistry (IHC) are need to be highly sensitive and specific. The IHC marker p40 (ΔNp63) is a truncated isoform of p63 that is a promising IHC marker for SQCC. In this study, we have compared the specificity of p40(ΔNp63) IHC with p63 and cytokeratin 5 (CK5) on fine-needle aspiration (FNA) cell blocks (CB). Thirty cases of pulmonary SQCC and 30 cases of pulmonary ADC with CB were selected. IHC for p40(ΔNp63), p63, and CK5 were performed on all paraffin-embedded CB serial sections. All cases (n = 30) of SQCC stained positive for p40(ΔNp63). All cases of bronchopulmonary ADC were negative for both p40(ΔNp63) and CK5. Six cases (20%) of bronchopulmonary ADC demonstrated nuclear staining for p63 in at least 10% of malignant cells. Our data support p40(ΔNp63) to be more sensitive and specific and possess a greater positive and negative predictive value for SQCC in comparison to p63. This study also documents that p40(ΔNp63) does not stain ADC, which p63 does in 20% of the cases. We also found that p40(ΔNp63) shows a greater sensitivity and negative predictive value when compared to CK5. In paucicellular CB the increased indices p40(ΔNp63) provides may be extremely helpful in confirming the diagnosis of SQCC, which may have significant therapeutic implications.

CDX-2 expression in malignant germ cell tumors of the testes, intratubular germ cell neoplasia, and normal seminiferous tubules.

CDX-2 is a caudal-type homeobox gene, encoding a transcription factor that plays an important role in proliferation and differentiation of intestinal epithelial cells. The utility of antibodies to CDX2 in the identification of adenocarcinomas of the gastrointestinal tract, particularly colorectal adenocarcinomas, in both primary and metastatic settings is well established. It is well-known that patients with testicular tumors may occasionally lack an obvious palpable mass. However, the expression of CDX2 in malignant germ cell tumors of the testes which have metastatic potential has not been previously studied in a large series. A tissue microarray was constructed from 52 malignant germ cell tumors of the testes including: 29 cases of classic seminoma, 8 cases of embryonal carcinoma, 8 cases of yolk sac tumor, 4 cases of malignant teratoma, 2 cases of choriocarcinoma, and 1 case of spermatocytic seminoma. Ten cases of intratubular germ cell neoplasia and seven cases of benign testicles with normal seminiferous tubules were also included in tissue microarray. Immunohistochemical stains for CDX2 was performed and analyzed. Only nuclear staining was considered positive. Positive expression of CDX2 was identified in 2/2 cases (100 %) of choriocarcinoma, 4/8 cases (50 %) of teratoma, 3/8 cases (38 %) of embryonal carcinoma, 3/8 cases (38 %) of yolk sac tumor, and 1/29 cases (3 %) of classic seminoma. CDX2 was negative in all cases of intratubular germ cell neoplasia, normal seminiferous tubules, and the only case of spermatocytic seminoma. The role of CDX-2 in the differentiation of intestinal/enteric epithelial cells may contribute to the formation of trophoblastic, glandular, villous, or cystic structures in germ cell tumors of the testes. This study suggests that the expression of CDX2 in a variety of malignant germ cell tumors of the testes may be a potential pitfall in metastatic tumors of unknown primary, which are thought to be of gastrointestinal/colorectal origin but are actually from a clinically occult testicular tumor.

Fascin as an identifier of metastatic urothelial carcinoma: A retrospective study of fine-needle aspiration cell blocks and histologic tissue microarrays.

Fascin, a marker of invasiveness in urothelial carcinoma, has not been correlated with metastatic disease. To enhance diagnostic accuracy and correctly identify primary site for appropriate patient management, fascin may be a useful marker in metastatic urothelial carcinoma. In this study, we evaluated twenty five cases with adequate cell block material for immunohistochemistry (IHC) staining in patients with either concurrent or previously resected urothelial carcinoma between 2005 and 2010. Fascin, thrombomodulin, uroplakin, cytokeratin 7, and cytokeratin 20 IHC were performed on paraffin-embedded cell block serial sections. Fascin was over-expressed in the majority (23/25, 92%) of metastatic urothelial carcinomas. We found concordant results in 22 of 25 (88%) cases for fascin and thrombomodulin IHC staining. Either fascin and/or thrombomodulin demonstrated positive staining in 25 of 25 (100%) cases. Histologic tissue microarrays of 72 genitourinary (GU) carcinomas of the kidney and prostate were stained with fascin to reveal all cases to be negative in the cells of interest. In comparing fascin with the traditional markers of urothelial carcinoma, fascin expression is of greater frequency and intensity than thrombomodulin. The combination of fascin and/or thrombomodulin identified all 25 (100%) cases of urothelial carcinoma. Fascin IHC staining is equivalent in frequency and intensity to cytokeratin 7. Fascin is an advantageous diagnostic complement, to thrombomodulin and/or cytokeratin 7, in the setting of metastatic urothelial carcinoma, and is highly specific and sensitive relative to GU malignancies.

Rete testis invasion by malignant germ cell tumor and/or intratubular germ cell neoplasia: what is the significance of this finding?

Pathologic stage and postsurgical treatment guidelines of malignant germ cell tumors, currently take into account angiolymphatic invasion, degree of extra testicular invasion, and serum tumor marker levels. The significance of rete testis invasion by malignant germ cell tumors or intratubular germ cell neoplasia however remains controversial. A search through the surgical pathology and expert consultation files at our institution from 2002 to 2009 was made for malignant germ cell tumors and intratubular germ cell neoplasia in orchiectomy specimens. Clinicopathologic data including rete testis status were obtained. Two hundred ninety-two orchiectomy specimens were identified. One hundred thirty-six were associated with malignant germ cell tumors. Mean patient age was 33 years (range, 14-67 years). The mean greatest tumor dimension was 4.1 cm (range, 0.8-18 cm). Fifty-six were pure seminoma (40%), 50 were nonseminomatous malignant germ cell tumors (35%), and 35 were mixed malignant germ cell tumors including a seminoma component (25%). Intratubular germ cell neoplasia was identified in 99 cases (70%). Pathologic stage at presentation was as follows: stage 1, 71 patients (50%); stage 2, 62 patients (45%); stage 3, 2 patients (1%); and indeterminate, 6 patients (4%). Seventy-eight patients had documented rete testis status: rete testis invasion, 41 (53%); no rete testis invasion, 37 (47%). Angiolymphatic invasion was present in 62 cases (44%). Follow-up information was available in 43 patients with known rete testis status. Mean follow-up duration was 43 months (range, 3-65 months). Twenty patients had rete testis invasion, and 23 patients had no rete testis invasion. Intratubular germ cell neoplasia was present in patients with rete testis invasion in 18 cases (90%), compared to only 13 cases (57%) in patients without rete testis invasion, P = .02. Serum markers were elevated in 10 patients (50%) with rete testis invasion compared to only 6 patients (26%) without rete testis invasion, P = .05. The combination of rete testis invasion and angiolymphatic invasion were present in 8 cases and were found to be associated with elevated serum tumor markers in 7 (88%) of the 8 cases, compared to the combination of no invasion of the rete testis and angiolymphatic invasion showing elevated serum tumor markers in 3 (38%) of 8 cases. However, 7 patients (35%) with rete testis invasion developed metastatic disease, and 11 patients (48%) without rete testis invasion developed metastatic disease. Rete testis status should be documented in orchiectomy specimens with malignant germ cell tumors. Intratubular germ cell neoplasia may be the only component of a malignant germ cell tumor involving the rete testis. In this series, elevated tumor markers were more likely associated with angiolymphatic invasion and positive rete testis status. Positive rete testis status does not appear to be an independent predictor of patient outcome.

Acute cholecystitis caused by nontoxigenic Vibrio cholerae O1 Inaba.

A rare case of acute cholecystitis caused by serogroup O1 Vibrio cholerae in an 83-year-old man is presented. His risk factors for cholecystitis included advanced age and previous abdominal surgeries. The patient had consumed raw oysters several days before presentation. The patient had a poor outcome after admission for this infection, likely due to his underlying illnesses that complicated his hospital course.