Littoral cell angioma of spleen: an uncommon presentation of a rare neoplasm.

Littoral cell angioma (LCA) is a rare primary splenic tumor that is difficult to differentiate preoperatively from other benign and malignant splenic lesions. Most of the cases present as multiple nodules in the spleen. We report a case of large solitary LCA of the spleen, an uncommon presentation. LCA should be considered in the differential diagnosis of multiple and solitary splenic lesions.

ERCC1 expression and outcomes in head and neck cancer treated with concurrent cisplatin and radiation.

BACKGROUND: Overexpression of excision repair cross complementing group 1 (ERCC1), a DNA repair enzyme, is associated with resistance to cisplatin. MATERIALS AND METHODS: Tissues from 73 patients with squamous cell carcinoma of the head and neck (HNSCC) who received concurrent cisplatin and radiation was analyzed immunohistochemically to determine if ERCC1 expression predicted for survival and response. Expression was scored as follows: 0=0% tumor nuclei positive, 1+=<50%, 2+=50-75% and 3+=>75%. RESULTS: ERCC1 expression was 0 in 0%, 1+ (14%), 2+ (42%) and 3+ (44%). In uni- and multivariate analyses, 3+ ERCC1 expression was not a significant predictor of survival or response. Median survival for the ERCC1 3+ patients was 2.9 years versus 2.1 years for the ERCC1 <3+ group (p=0.44). CONCLUSION: In this retrospective review of HNSCC patients receiving concurrent cisplatin and radiation, ERCC1 expression was not a significant predictor of survival or response.

Phosphorylated histone H3, Ki-67, p21, fatty acid synthase, and cleaved caspase-3 expression in benign and atypical granular cell tumors.

CONTEXT: Granular cell tumors (GCTs) are classified as benign when none of the following features is present: spindling of the tumor cells, necrosis, diffuse pleomorphism, prominent nucleoli, high nuclear-cytoplasmic ratio, and mitotic rate >2 per 10 high-power fields. It has been suggested that a GCT be classified as atypical when 1 or 2 of these features are seen and as malignant when 3 or more of these are present. In our practice, we do not classify GCTs as malignant in the absence of metastasis. OBJECTIVE: To compare immunohistochemical staining for phosphorylated histone H3 (PHH3), Ki-67 (MIB-1), p21, fatty acid synthase, and cleaved caspase-3 in histologically classified benign and atypical GCTs. DESIGN: We reviewed 25 cases of GCT from our archives and classified 14 as atypical based on histologic features. Immunohistochemical staining for PHH3, Ki-67, p21, fatty acid synthase, and cleaved caspase-3 was performed using standard methods. The number of positive cells for Ki-67, p21, and PHH3 was calculated in 10 consecutive high-power fields in a hot spot. Fatty acid synthase and cleaved caspase-3 cytoplasmic expression was graded from 1 to 3. RESULTS: Ki-67 and PHH3 scores were significantly higher in atypical GCTs. The expression of p21, fatty acid synthase, and cleaved caspase-3 was not significantly different between atypical and benign GCTs. CONCLUSIONS: This study shows that histologic features are reliable in identifying GCTs that have a higher proliferative potential as shown by higher immunoreactivity for Ki-67 and PHH3. These immunostains may help in classifying GCTs in cases where a thorough histologic evaluation is precluded by the small size of a biopsy specimen.

Intestinal and oncocytic variants of pancreatic intraepithelial neoplasia. A morphological and immunohistochemical study.

We report 2 previously undescribed morphological variants of pancreatic intraepithelial neoplasia (PanIN). The first variant with an intestinal phenotype was associated with mucinous carcinomas that occurred in the tail of the pancreas of 2 men (60 and 65 years old). The carcinomas lacked the characteristic ovarian-like stroma of mucinous cystic neoplasms observed in female patients and did not show a papillary architecture. Whether they represent mucinous cystadenocarcinomas or mucinous carcinomas that arose from the flat variant of intraductal papillary mucinous neoplasms could not be determined with certainty. Microscopically, the intestinal type of PanIN was composed of pseudostratified columnar cells similar to those of colonic adenomas and showing variable degrees of dysplasia. A significant increase in the MIB-1 labeling index correlated with the severity of dysplasia. In contrast to conventional PanIN, the intestinal variant expressed MUC-2 and was MUC-1 negative. The second type of PanIN had an oncocytic phenotype, coexpressed MUC-2 and MUC-1 mucins, and was associated with intraductal oncocytic papillary carcinomas that showed a similar immunohistochemical mucin profile. Both intestinal and oncocytic types of PanIN expressed DPC4 and lacked p53 reactivity. The anatomical separation of the PanINs from the carcinomas and the gradual progression of cytological and architectural abnormalities in both variants of PanIN argue against ductal spread (cancerization of the ducts). The intestinal and oncocytic variants of PanIN broaden the morphological spectrum of this intraductal lesion. Although their significance is unknown, the possibility that these PanIN variants represent cancer precursors should be considered.

Survival in small cell lung cancer is independent of tumor expression of VEGF and COX-2.

BACKGROUND: Preclinical data suggests that VEGF and COX-2 are potentially important mediators in the pathogenesis of small cell lung cancer (SCLC). Little is known about the frequency of tumor expression of VEGF and COX-2 in SCLC or the prognostic significance of this expression. MATERIALS AND METHODS: Clinical records from 54 cases of SCLC were reviewed. Immunohistochemical stains for VEGF and COX-2 were performed on all tumor specimens. RESULTS: Tumor VEGF expression was detected in 43 cases (81%) and COX-2 expression in 11 (20%). No significant association between VEGF or COX-2 expression and survival was observed. CONCLUSION: This is the first study to assess the frequency and clinical significance of tumor VEGF and COX-2 expression in a large group of patients with SCLC. In this cohort, neither VEGF nor COX-2 expression impacted survival. The frequency of VEGF expression suggests that it merits further investigation as a therapeutic target in SCLC.

Malignant melanoma with a rhabdoid phenotype: histologic, immunohistochemical, and ultrastructural study of a case and review of the literature.

Malignant melanoma is known to display tremendous histologic diversity. One rare variant is the rhabdoid phenotype, so called because of the appearance of cells resembling rhabdomyoblasts seen in malignant rhabdoid tumors of the kidney. We present the histologic, immunohistochemical, and ultrastructural features of a malignant melanoma composed entirely of rhabdoid cells. A 62-year-old man presented with a 6.5-cm lung mass. Although presumed to be a metastatic lesion, extensive workup failed to reveal a primary tumor site. Histologic sections showed a mass composed entirely of polygonal neoplastic cells with prominent nucleoli and large hyaline cytoplasmic inclusions. The tumor cells were strongly immunoreactive with S100 protein, vimentin, and CD56, and were focally reactive with Mart-1. Tumor cells were negative for Melan-A, tyrosinase, HMB-45, AE1/AE3, cytokeratin (CK) 7, CK8/ 18, CK20, CK903, CAM 5.2, epithelial membrane antigen, smooth muscle actin, desmin, leukocyte common antigen, Bcl-2, CD3, CD20, CD30, CD138, kappa and lambda light chains, CD68, CD34, factor VIII, synaptophysin, and glial fibrillary acidic protein. Electron microscopy showed cytoplasmic whorls of intermediate filaments containing entrapped rough endoplasmic reticulum, mitochondria, and lipid. Recognition of this rare variant of malignant melanoma is important in the evaluation of tumors with rhabdoid morphology.

Inhibin alpha distinguishes hemangioblastoma from clear cell renal cell carcinoma.

Inhibin alpha subunit (inhibin A) expression in hemangioblastomas has not been previously reported in the literature. We analyzed the expression of inhibin A in 25 hemangioblastomas from 22 patients. Eleven cases were from 8 patients with von Hippel-Lindau disease, and these tumors were multicentric and/or recurrent. The remaining 14 cases from 14 patients were sporadic. The male-to-female ratio was 8:3, and the age at presentation ranged from 19 to 78 years (mean 35 years; median 45 years). Eighteen tumors were located in the cerebellum/posterior fossa, 1 in the medulla, 1 in the occipital lobe, and 5 in the spinal cord. Four metastatic renal cell carcinomas in brain, 10 renal cell carcinomas from 8 patients with von Hippel-Lindau disease, and 5 sporadic clear cell renal cell carcinomas were also included. Two patients with von Hippel-Lindau disease had both renal cell carcinoma and hemangioblastoma. The stromal cells of all 25 cases of hemangioblastoma expressed inhibin A. Strong, moderate, and weak cytoplasmic immunoreactivity was noted in 17, 5, and 3 cases, respectively. In contrast, none of the 19 renal cell carcinomas, primary as well as metastatic, expressed inhibin A. There was no difference in the inhibin A staining pattern between the sporadic hemangioblastoma and those associated with VHL. These findings demonstrate inhibin A to be a useful marker in distinguishing hemangioblastoma from metastatic clear cell renal cell carcinoma. While the diagnostic importance is evident, the pathophysiology of inhibin A expression by the stromal cells of hemangioblastoma remains unknown and further investigation is required.

Cystic sebaceous neoplasms in Muir-Torre syndrome.

Cystic sebaceous neoplasms have been seen only in patients with Muir-Torre syndrome (MTS) and have recently been characterized as marker lesions of MTS. Histologically, these lesions form a spectrum of tumors ranging from benign cystic adenomas to proliferative cystic sebaceous tumors. We describe 2 proliferative cystic sebaceous tumors in a 53-year-old man whose workup revealed colonic adenocarcinoma and other sebaceous tumors consistent with MTS. Both the chest wall and the left thigh masses were grossly cystic, measuring 1.0 and 1.5 cm, respectively. Histologic sections demonstrated well-circumscribed cystic neoplasms located in the deep dermis and subcutaneous tissue. Each had a focally infolded cyst wall composed of immature basaloid cells with prominent nucleoli and mitoses, consistent with a proliferative cystic sebaceous tumor. Recognition of cystic sebaceous neoplasm by pathologists and communication to clinicians of its strong association with MTS is of diagnostic importance.

Rosette formation within a proliferative nodule of an atypical combined melanocytic nevus in an adult.

Rosette formation is a feature that has not been described as occurring in melanocytic neoplasms. We present such a unique case. A 59-year-old man presented with an asymptomatic, soft, hairy 3.0 x 2.0-cm pigmented lesion that had been present for many years in the right external ear, extending from the conchal bowl onto the antitragus area. Examination of histologic sections showed a proliferation of nonatypical and heavily pigmented melanocytes in the superficial dermis and around deep adnexal structures, characteristic of a congenital nevus. In other areas, pigmented spindled and dendritic cells infiltrated thickened collagen bundles in a pattern of a blue nevus. A nodular proliferation of epithelioid melanocytes was seen within the deep dermis and subcutaneous tissue. The periphery of the nodule merged with the surrounding nevus cells. Neoplastic cells with nuclear atypia, melanin pigment, pseudonuclear inclusions, and balloon cell change were present. In addition, there was rosette formation by the tumor cells, with a central aggregate of coarse cell processes. Neuroid cords were also noted. No prominent mitotic figures, necrosis, or significant inflammatory infiltrate were noted. The neoplastic cells were positive for S-100 protein, Mart-1, tyrosinase, neuron-specific enolase, and vimentin. HMB-45 and Ki-67 (MIB-1) labeled only rare neoplastic cells within the proliferative nodule. The tumor cells were negative for synaptophysin, protein gene product 9.5, CD57, epithelial membrane antigen, CD31, and CD34. The central cell processes of the rosettes were negative for trichome, type IV collagen, neurofilament protein, glial fibrillary acidic protein, and tyrosine hydroxylase. We also retrospectively examined 78 congenital nevi of 65 pediatric patients at our institution. Rosette formation was not seen in any of these cases.

Effectiveness and safety of image-directed biopsies: coaxial technique versus conventional fine-needle aspiration.

BACKGROUND: We compared the effectiveness and safety of image-guided biopsies done with coaxial guides versus fine-needle aspiration done without coaxial guides. METHODS: With the use of hospital computer records and chart reviews, all image-guided biopsies done during a 4-year period at our institution were assessed for adequacy and complications. For each biopsy, the use of a coaxial guide, the site, and the imaging modality were recorded. Adequacy of the biopsy and complications were compiled. Success rates were calculated for conventional and coaxial biopsies and by modality and site. RESULTS: Coaxial technique reduced the number of unsatisfactory biopsies compared with conventional technique in extrathoracic sites. The decrease was statistically significant. No major complications occurred from extrathoracic biopsies with either technique. No difference was found in success rates or complication rates between ultrasound-guided and CT-guided biopsies using coaxial technique. CONCLUSION: Coaxial technique reduces the number of inadequate biopsies in extrathoracic sites, without a detectable increase in complications.