Showing papers in "The American Journal of Surgical Pathology in 2004"

An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms

Abstract: Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease. Several distinct noninvasive precursor lesions can give rise to invasive adenocarcinoma of the pancreas, and the prevention, detection, and treatment of these noninvasive lesions offers the potential to cure early pancreatic cancers. Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Diagnostic criteria, including a distinct ovarian-type stroma, and a consistent nomenclature are well established for mucinous cystic neoplasms. By contrast, consistent nomenclatures and diagnostic criteria have been more difficult to establish for PanINs and IPMNs. Because both PanINs and IPMNs consist of intraductal neoplastic proliferations of columnar, mucin-containing cells with a variable degree of papilla formation, the distinction between these two classes of precursor lesions remains problematic. Thus, considerable ambiguities still exist in the classification of noninvasive neoplasms in the pancreatic ducts. A meeting of international experts on precursor lesions of pancreatic cancer was held at The Johns Hopkins Hospital from August 18 to 19, 2003. The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms. We present a consensus classification of the precursor lesions in the pancreatic ducts, PanINs and IPMNs.

Grading ovarian serous carcinoma using a two-tier system.

Abstract: In this study, we evaluate a two-tier system for grading ovarian serous carcinoma. This system is based primarily on the assessment of nuclear atypia with the mitotic rate used as a secondary feature. The study included 50 cases of low-grade ovarian serous carcinoma and 50 cases of high-grade ovarian serous carcinoma retrieved from the files of the Department of Pathology at the University of Texas M. D. Anderson Cancer Center from a 28-year period. Cases assigned to the low-grade category were characterized by the presence of mild to moderate nuclear atypia. As a secondary feature, they tended to show up to 12 mitoses per 10 high power fields (HPFs), whereas those in the high-grade category had marked nuclear atypia and as a secondary feature more than 12 mitoses per 10 HPFs. For comparison, the tumors were also graded using the Shimizu/Silverberg and the FIGO grading systems. Patients in the low-grade ovarian serous carcinoma group ranged in age from 19 to 75 years (mean 41.7 years) while patients in the high-grade ovarian serous carcinoma group ranged in age from 27 to 76 years (mean 55 years). All of the cases except one were advanced FIGO stage. Using the Shimizu/Silverberg system, the low-grade ovarian serous carcinoma cases were distributed as follows: grade 1, 47 cases; grade 2, 3 cases. Using the FIGO grading system, 35 cases were grade 1 and 15 cases were grade 2. Regarding the high-grade ovarian serous carcinoma group using the Shimizu/Silverberg system, 14 of the cases were grade 2 and 36 cases were grade 3. Using the FIGO grading system, 1 case was grade 1, 38 cases were grade 2, and 11 cases were grade 3. Most of the patients in both groups were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy and also received cisplatinum-based chemotherapy. On follow-up, 37 patients in the low-grade ovarian serous carcinoma group had died of disease at a median 4.2 years after diagnosis compared with 46 patients in the high-grade ovarian serous carcinoma group who died of disease at a median of 1.7 years. Eight patients in the low-grade ovarian serous carcinoma group and 4 patients in the high-grade ovarian serous carcinoma group were alive with disease at median follow-ups of 4.3 and 3.85 years, respectively. Four patients with low-grade serous carcinoma were alive without evidence of disease after a follow-up that ranged from 4.4 to 22.6 years (median 6.85 years), and one died of other causes 14 years after the diagnosis of her ovarian tumor. On multivariate analysis, residual tumor and tumor grade based on the M. D. Anderson two-tier system for grading ovarian serous carcinoma were found to be significant independent prognostic factors (P = 0.003 and 0.04, respectively). Of interest, 60% of the low-grade ovarian serous carcinomas in this study were associated with a serous neoplasm of low malignant potential, whereas this association was present in only 2% of the high-grade ovarian serous carcinomas. This finding could reflect a difference in the pathogenesis of ovarian serous carcinomas of different grades. In summary, there is usually a good correlation between the two-tier grading system herein presented and the Shimizu/Silverberg and the FIGO grading systems. Because this system is based on defined criteria that are easy to follow and because it involves only two diagnostic categories, it should provide better reproducibility in the grading of ovarian serous carcinoma. However, additional studies are required to validate these statements.

Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature.

Abstract: Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due to phosphate wasting The phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently associated with OO Despite its association with OO, many PMTMCTs go unrecognized because they are erroneously diagnosed as other mesenchymal tumors Expression of fibroblast growth factor-23 (FGF-23), a recently described protein putatively implicated in renal tubular phosphate loss, has been shown in a small number of mesenchymal tumors with known OO The clinicopathological features of 32 mesenchymal tumors either with known OO (29) or with features suggestive of PMTMCT (3) were studied Immunohistochemistry for cytokeratin, S-100, actin, desmin, CD34, and FGF-23 was performed The patients (13 male, 19 female) ranged from 9 to 80 years in age (median 53 years) A long history of OO was common The cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3), osteosarcoma (3), giant cell tumor (2), and other (9) The tumors occurred in a variety of soft tissue (21) and bone sites (11) and ranged from 17 to 14 cm Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels, microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous ossification Four of these benign-appearing PMTMCTs contained osteoid-like matrix Three other PMTMCTs were hypercellular and cytologically atypical and were considered malignant The 3 cases without known OO were histologically identical to the typical PMTMCT Four cases did not resemble PMTMCT: 2 sinonasal HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma Three cases expressed actin; all other markers were negative Expression of FGF-23 was seen in 17 of 21 cases by immunohistochemistry and in 2 of 2 cases by RT-PCR Follow-up (25 cases, 6-348 months) indicated the following: 21 alive with no evidence of disease and with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung metastases) We conclude that most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT Improved recognition of their histologic spectrum, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should allow distinction from other mesenchymal tumors Recognition of PMTMCT is critical, as complete resection cures intractable OO Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in PMTMCT-associated OO

IgG4-related sclerosing cholangitis with and without hepatic inflammatory pseudotumor, and sclerosing pancreatitis-associated sclerosing cholangitis : Do they belong to a spectrum of sclerosing pancreatitis?

Abstract: Sclerosing cholangitis (SC) is a heterogeneous disease entity. Different etiologies such as choledocholithiasis, biliary tumor, or pericholangitis can manifest as SC. Hepatic inflammatory pseudotumor (IP) is rarely associated with SC (sclerosing cholangitis associated with hepatic inflammatory pseudotumor; SC-hepatic IP), but sclerosing pancreatitis (SP) is not infrequently associated with bile duct lesions (sclerosing pancreatitis-associated sclerosing cholangitis; SP-SC). In this study, we compared the histologic changes of hepatic hilar and extrahepatic bile duct lesions of SC (7 cases), SC-hepatic IP (5 cases), SP-SC (5 cases), and typical primary sclerosing cholangitis (PSC) (5 cases). Histologically, all SP-SC cases showed extensive and dense fibrosis with marked lymphoplasmacytic infiltration, many eosinophils, and obliterative phlebitis. Four cases of SC showed bile duct lesions similar to those of SP-SC, whereas other three cases of SC showed milder lymphoplasmacytic infiltration, scant eosinophilic cell infiltration, and no obliterative phlebitis. All SC-hepatic IP cases showed bile duct lesions identical to those of SP-SC. Immunohistochemically, many IgG4-positive plasma cells were found in the bile duct lesions of all SP-SC cases, 4 SC cases with marked lymphoplasmacytic infiltration, and all SC-hepatic IP cases. By contrast, IgG4-positive plasma cells were scarce or hardly found in the remaining 3 SC cases and all PSC cases. In conclusion, 4 SC cases and all SC-hepatic IP cases showed bile duct lesions identical to those of SP-SC, suggesting that these three conditions may be a single disease entity. Their pathogenesis may be similar or closely related to that of SP, and in that respect they may represent an IgG4-related biliary disease. They may respond to steroid therapy as SP does.

KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications.

Abstract: The diagnosis of gastrointestinal stromal tumor (GIST) is currently based on morphologic features and immunohistochemical demonstration of KIT (CD117). However, some tumors (in our estimation approximately 4%) have clinicopathologic features of GIST but do not express KIT. To determine if these lesions are truly GISTs, we evaluated 25 tumors with clinical and histologic features typical of GIST, but with negative KIT immunohistochemistry, for KIT and PDGFRA mutations using DNA extracted from paraffin-embedded tissue. Most tumors originated in the stomach (N = 14) or omentum/mesentery (N = 5). The neoplasms were composed of epithelioid cells (13 cases), admixed epithelioid and spindle cells (8 cases), or spindle cells (4 cases). Absence of KIT expression was confirmed by immunoblotting in 5 cases. Tumor karyotypes performed in 4 cases were noncomplex with monosomy 14 or 14q deletion, typical of GIST. Mutational analysis revealed PDGFRA and KIT mutations in 18 and 4 tumors, respectively, whereas 3 tumors did not have apparent KIT or PDGFRA mutations. The PDGFRA mutations primarily involved exon 18 (N = 15) and included 11 tumors with missense mutation in codon 842 (PDGFRA D842V or D842Y). In conclusion, a small subset of GISTs with otherwise typical clinicopathologic and cytogenetic features do not express detectable KIT protein. When compared with KIT-positive GISTs, these KIT-negative GISTs are more likely to have epithelioid cell morphology, contain PDGFRA oncogenic mutations, and arise in the omentum/peritoneal surface. Notably, some KIT-negative GISTs contain imatinib-sensitive KIT or PDGFRA mutations; therefore, patients with KIT-negative GISTs should not, a priori, be denied imatinib therapy.

Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma

Abstract: The histopathologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) can be difficult. Recent reports have suggested that this neoplasm may be frequently overdiagnosed by pathologists. We examined the observer variation in the diagnosis of FVPCA in 87 tumors by 10 experienced thyroid pathologists. The criteria that the reviewers considered most helpful for making a diagnosis of FVPCA were also assessed. A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39%. In this series, 24.1% of the patients had metastatic disease (n = 21). In the cases with metastatic disease, a diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 66.7%, and 7 of the reviewers made a diagnosis of FVPCA with a cumulative frequency of 100%. The most important criteria used to diagnose FVPCA included the presence of cytoplasmic invaginations into the nucleus (pseudo-inclusions), abundant nuclear grooves, and ground glass nuclei. These results suggest that although the diagnosis of FVPCA is variable even among experienced thyroid pathologists, most reviewers agreed on this diagnosis for patients with metastatic disease. The use of well-defined histopathologic features should improve the consistency in diagnosing FVPCA. Since most cases with metastatic disease had obvious invasion, caution should be used in making a diagnosis of FVPCA in the absence of the major histopathologic features or clear-cut invasive growth.

Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms: delineation of an "intestinal" pathway of carcinogenesis in the pancreas.

Abstract: Although general characteristics of intraductal papillary mucinous neoplasms (IPMNs) and their delineation from other pancreatic tumors have been well established, several issues regarding their biology and management remain unresolved. It has been noted briefly by us and other authors that there are different types of papillae in IPMNs; however, their frequency, biologic significance, and clinical relevance are unknown. In this study, the association of different papillary patterns with clinical, pathologic, and biologic parameters was studied in 74 IPMNs, and the expression profile of CDX2 (a specific marker and one of the key determinants of intestinal "programming," and a tumor suppressor) was determined immunohistochemically in addition to MUC1 (a marker of an "aggressive" phenotype in pancreatic neoplasia) and MUC2 ("intestinal type mucin," a marker of the "indolent" phenotype, and a tumor suppressor). The patterns of papillae identified and their association with these parameters were as follows: 1) The intestinal-type (Yonezawa's dark-cell type), similar to villous adenomas, was seen in 26 of 74 (35%) cases. The majority harbored carcinoma in situ (85%) or borderline atypia (15%). They tended to be large (mean, 5.5 cm). Most expressed CDX2 (95%) and MUC2 (92%) but not MUC1 (8%). This type was more commonly associated with colloid-type invasion (14 of 16 invasive carcinomas were of colloid type). 2) The pancreatobiliary type, characterized by arborizing papillae lined by cuboidal cells resembling papillary neoplasms of the biliary tract, was present in 22% of the cases. These were mostly graded as carcinoma in situ (94%); they rarely expressed CDX2 (6%) or MUC2 (19%) but often showed MUC1 labeling (44%). This pattern was more commonly associated with the tubular type of invasive carcinoma and had a slight tendency for a more aggressive clinical course. 3) The null type was characterized by abundant apical mucin and basally located nuclei, similar to the gastric foveolar epithelium. Thirty-one percent of IPMNs had this type of papillae, but this pattern was also present in the background of other IPMNs and in the cystic components of most cases as well. Most pure null-type IPMNs were devoid of complexity and consequently classified as adenoma (48%). They tended to be small (mean, 2.6 cm), were often negative for CDX2, MUC1, and MUC2, and were rarely associated with invasive carcinoma. 4) Some IPMNs (12%) exhibited features that were difficult to classify, and 2 cases had a mixture of pancreatobiliary and intestinal types of papillae. In conclusion, IPMNs include pathologically and biologically distinct epithelial patterns. CDX2 and MUC2 expression is relatively specific for the intestinal type papillae, confirming that these IPMNs indeed exhibit intestinal differentiation. Their close association with colloid carcinoma, which also shows consistent MUC2 and CDX2 expression, supports the existence of an intestinal pathway of carcinogenesis. This "metaplastic" pathway may reflect different genetic events in the development of these IPMNs, and the presence of intestinal differentiation may potentially be used in prognostication and stratification of patients into appropriate treatment categories.

Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities.

Abstract: Plasmablastic lymphoma was initially described as a variant of diffuse large B-cell lymphoma (DLBCL) involving the oral cavity of HIV+ patients and characterized by immunoblastic morphology and a plasma cell phenotype. However, other lymphomas may exhibit similar morphologic and immunophenotypic features. To determine the significance of plasmablastic differentiation in DLBCL and examine the heterogeneity of lymphomas with these characteristics, we examined 50 DLBCLs with low/absent CD20/CD79a and an immunophenotype indicative of terminal B-cell differentiation (MUM1/CD38/CD138/EMA-positive). We were able to define several distinct subgroups. Twenty-three tumors were classified as plasmablastic lymphoma of the oral mucosa type and showed a monomorphic population of immunoblasts with no or minimal plasmacytic differentiation. Most patients were HIV+ and EBV was positive in 74%. Eleven (48%) cases presented in the oral mucosa, but the remaining presented in other extranodal (39%) or nodal (13%) sites. Sixteen cases were classified as plasmablastic lymphoma with plasmacytic differentiation. These were composed predominantly of immunoblasts and plasmablasts, but in addition exhibited more differentiation to mature plasma cells. Only 33% were HIV+, EBV was detected in 62%, and 44% had nodal presentation. Nine cases, morphologically indistinguishable from the previous group, were secondary extramedullary plasmablastic tumors occurring in patients with prior or synchronous plasma cell neoplasms, classified as multiple myeloma in 7 of the 9. Two additional neoplasms were an HHV-8+ extracavitary variant of primary effusion lymphoma and an ALK+ DLBCL. HHV-8 was examined in 39 additional cases, and was negative in all. In conclusion, DLBCLs with plasmablastic differentiation are a heterogeneous group of neoplasms with different clinicopathological characteristics that may correspond to different entities.

Sarcomatoid renal cell carcinoma: an examination of underlying histologic subtype and an analysis of associations with patient outcome.

Abstract: A sarcomatoid component can occur in all histologic subtypes of renal cell carcinoma (RCC) and indicates an aggressive tumor. We studied 2381 patients treated with radical nephrectomy for RCC between 1970 and 2000. A urologic pathologist reviewed the microscopic slides from all tumor specimens for the presence of a sarcomatoid component, defined as a RCC with any malignant spindle cell component. All tumors with a sarcomatoid component were classified as nuclear grade 4. A total of 120 (5.0%) patients had RCC with a sarcomatoid component, including 94 who died of RCC at a mean of 1.4 years following nephrectomy (median 8 months; range 44 days to 10 years). Cancer-specific survival rates at 2 and 5 years following nephrectomy were 33.3% and 14.5%, respectively. The presence of distant metastases at the radical nephrectomy and histologic tumor necrosis were significantly associated with death from RCC among patients with sarcomatoid RCC. Patients with clear cell (conventional) RCC and chromophobe RCC were more likely to have tumors with a sarcomatoid component (5.2% and 8.7%, respectively) compared with patients with papillary RCC (1.9%). The presence of a sarcomatoid component was significantly associated with death from RCC for all three subtypes (P < 0.001). Even among patients with grade 4 clear cell RCC, the presence of a sarcomatoid component was significantly associated with outcome, both univariately (risk ratio 1.59; P = 0.010) and after adjusting for TNM stage, tumor size, and histologic tumor necrosis (risk ratio 1.46; P = 0.037).

Immunohistochemical analysis of hSNF5/INI1 in pediatric CNS neoplasms.

Abstract: Atypical teratoid/rhabdoid tumor (AT/RT) may be misdiagnosed as primitive neuroectodermal tumor/medulloblastoma (PNET) and occasionally as other tumors. Molecular genetic analysis of AT/RT demonstrates deletion and mutation of the hSNF5/INI1 gene in most cases, with decreased or absent expression at the RNA or protein level. Immunohistochemistry with an antibody to INI1 was performed to determine whether this would be a sensitive and specific means of assessing INI1 loss in pediatric brain tumors. Fifty-three tumors consisting of 20 AT/RTs, 10 PNETs, and 23 other central nervous system tumors were examined. No nuclear staining was found in all 20 AT/RTs. Most other central nervous system tumors demonstrated nuclear staining. Eight cases in which classification as AT/RT or PNET was difficult were also examined. Seven cases had no chromosome 22 deletion or INI1 mutation; INI1 antibody showed nuclear staining in these cases. One case was a recurrent tumor with features consistent with an AT/RT. INI1 immunostaining was negative in this case, and a mutation in INI1 was subsequently identified. Immunohistochemical staining with an INI1 antibody correlates with molecular findings in AT/RT and may be useful in confirming the histologic diagnosis. INI1 immunostaining may have particular utility in the analysis of tumors with indeterminate histologic features or atypical immunophenotypic profiles.

Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma.

Abstract: Kaposiform hemangioendothelioma (KH) is a rare tumor of childhood often associated with Kasabach-Merritt phenomenon (KMP) and occasionally lymphangiomatosis. Although generally considered distinct from other vascular neoplasms, its rarity has precluded a thorough study of its immunophenotypic profile and long-term behavior. Thirty-three cases of KH were reviewed and immunostained for alpha-smooth muscle actin, various endothelial markers (CD31, CD34, vWf, FLI1), a platelet marker (CD61), and the juvenile hemangioma-associated markers GLUT-1 and Lewis Y antigen (LeY). In addition, the presence of HHV-8 was evaluated by RT-PCR. The patients (20 males and 13 females) ranged in age from 2 weeks to 20 years (mean 3 years 9 months). Tumors developed on the extremities (17 cases), head/neck (8 cases), and other sites (8 cases) and affected both superficial and deep soft tissue. Those in the skin presented as slightly raised blue-red lesions. More than half of the patients presented with KMP (14 of 25). Tumors consisted of irregular, infiltrating nodules of compressed vessels, which modulated between areas resembling a capillary hemangioma and Kaposi sarcoma (KS). Endothelial cells in nodules were CD31, CD34, and FLI1 positive but negative for GLUT1 and LeY. Scattered "epithelioid" or glomeruloid islands featuring endothelium associated with clusters of plump alpha-smooth muscle actin-positive pericytes, stippled hemosiderin, and CD61-positive fibrin thrombi likely represent the morphologic sites of platelet consumption. Small and large lymphatic channels occurred in 22 of 33 cases and were typically seen peripheral or deep to the main tumor mass. HHV-8 transcripts were not identified (0 of 3 cases). Follow-up information was available in 22 patients (range 8 months to 15 years; mean 2 years) and indicated that 3 died of disease, 8 were alive with disease, and 10 were alive without residual disease. Two patients developed regional perinodal soft tissue involvement, but none developed distant metastases. KH is a lesion having both a vascular and lymphatic component. Its common association with KMP probably relates in part to unique architectural features that favor turbulent blood flow and platelet activation. KH can also be reliably separated from JH by GLUT-1 and LeY immunostaining, indicating differences in the morphologic and functional attributes of the endothelium between the two lesions. The absence of HHV-8 in KH underscores a different pathogenesis from Kaposi sarcoma. Our study, the largest to date, emphasizes that mortality is due to KMP and not metastatic disease, which appears limited to regional perinodal soft tissue. Given this behavior, its continued classification as a vascular tumor of intermediate malignancy is warranted.

Kimura Disease: A Clinicopathologic Study of 21 Cases

Abstract: :Kimura disease is a rare form of chronic inflammatory disorder involving subcutaneous tissue, predominantly in the head and neck region and frequently associated with regional lymphadenopathy and/or salivary gland involvement. This condition has a predilection for males of Asian descent and

BRAF and KRAS Mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status.

Abstract: The aim of this study was to test the hypothesis that mutations of the oncogenes BRAF or KRAS are early events in the putative serrated polyp neoplasia pathway and more advanced pathology is associated with acquired mutator and suppressor gene inactivation by CpG island methylation of promoter regions. We assayed 79 sporadic hyperplastic polyps (HPs) classified according to the schema of Torlakovic et al and 25 serrated adenomas (SAs) for BRAF and KRAS mutations and related the findings to histologic characteristics and CpG island methylation phenotype (CIMP). Mutations at exon 15, codon 599, of BRAF were assayed using an allele-specific PCR (AS-PCR) technique and confirmed in a sample of AS-PCR- positive cases by direct sequencing of exon 15. AS-PCR-negative HPs and SAs were also sequenced on exon 15 and exon 11 to detect additional mutations. PCR-RFLP was used to assay KRAS codon 12 and 13 mutations, and these mutations were further validated by direct sequencing of the KRAS gene. BRAF599 mutations were identified in a total of 55 HPs (69.6%) and KRAS mutations in a total of 13 (16.5%). BRAF599 mutations occurred with similar frequencies among microvesicular serrated polyp (76.3%) and serrated polyp with abnormal proliferation (82.1%) subtypes but less frequently in goblet cell serrated polyps (23.1%). Conversely, KRAS mutations were most frequent in goblet cell serrated polyp (46.2%) and less frequent in microvesicular serrated polyp (13.2%) and serrated polyp with abnormal proliferation (7.1%). BRAF599 and KRAS mutations were present in 15 (60.0%) and 7 (28.0%) of SAs, respectively. BRAF 599 mutation and KRAS were mutually exclusive findings in the polyps studied and one or the other occurred in 68 of 79 (86.1%) HPs and 22 of 25 (88.0%) SAs. CpG island methylation involving 2 or more genes (CIMP-H) was present in 80.0% of SAs, 75% serrated polyp with abnormal proliferations, 47.4% of microvesicular serrated polyps, and 15.4% of goblet cell serrated polyps. SAs were significantly more likely to be CIMP-H than HPs (odds ratio 3.7; 95% confidence interval, 1.27-10.86; P = 0.017). A similar high frequency of KRAS or BRAF mutations across the histologic spectrum of the serrated polyps assayed suggests that these are early events in the serrated polyp neoplasia pathway. In contrast, the association of higher levels of CpG island methylation with more advanced histologic changes suggests that CpG island methylation plays a role in serrated polyp progression toward colorectal carcinoma.

Immunohistochemical analysis of hSNF5/INI1 distinguishes renal and extra-renal malignant rhabdoid tumors from other pediatric soft tissue tumors.

Abstract: Malignant rhabdoid tumor (MRT) is a highly aggressive neoplasm that occasionally demonstrates phenotypic overlap with other soft tissue malignancies. Molecular genetic analysis of MRT frequently demonstrates deletion or mutation of the hSNF5/INI1 gene, with corresponding reduced expression at the protein level. INI1 immunohistochemistry was performed to determine the utility of this method in assessing loss of INI1 expression in rhabdoid tumors. Twenty-seven MRTs with molecular analysis (19 renal, 8 extra-renal) were evaluated. Seventeen additional MRT (10 renal, 7 extra-renal) without INI1 molecular analysis were also analyzed. Loss of INI1 expression was observed in the tumor cells in all 44 cases. To determine the specificity of this assay, a variety of 45 pediatric soft tissue tumors, some of which occasionally display rhabdoid differentiation, were investigated. These included Ewing's sarcoma, Wilms' tumor, desmoplastic small round cell tumor, clear cell sarcoma, congenital mesoblastic nephroma, synovial sarcoma, undifferentiated sarcoma, rhabdomyosarcoma, and epithelioid sarcoma. Positive nuclear staining was found in all nonrhabdoid tumors examined. Of interest, synovial and epithelioid sarcomas exhibited variable and/or focal staining. INI1 antibody immunohistochemistry is useful in confirming the histologic diagnosis of renal or extra-renal rhabdoid tumor, especially for cases with indeterminate histologic features, equivocal immunophenotypic profiles, or uninformative molecular studies.

KSHV-positive solid lymphomas represent an extra-cavitary variant of primary effusion lymphoma.

Abstract: Primary effusion lymphoma (PEL) is a unique form of non-Hodgkin lymphoma (NHL) associated with Kaposi sarcoma-associated herpesvirus (KSHV; HHV-8) that displays a distinct constellation of clinical, morphologic, immunologic, and molecular characteristics. Rare KSHV-containing immunoblastic lymphomas occurring in solid tissues have been described. Whether they represent part of the spectrum of PEL has not been determined. The morphologic, immunophenotypic, and molecular features of KSHV-positive solid lymphomas occurring in 8 HIV+/AIDS patients were systematically investigated and compared with those of 29 similarly analyzed PELs. The 8 KSHV-positive solid lymphomas were virtually indistinguishable from the 29 PELs based on morphology (immunoblastic/anaplastic), immunophenotype (CD45 positive; T cell antigen negative; CD30, EMA, CD138 positive; CD10, CD15, BCL6 negative) and genotype (100% immunoglobulin genes rearranged; no identifiable abnormalities in C-MYC, BCL6, BCL1, BCL2; and uniformly EBV positive). The only identifiable phenotypic difference was that the KSHV-positive solid lymphomas appeared to express B cell-associated antigens (25%) and immunoglobulin (25%) slightly more often than the PELs (<5% and 15%, respectively; P = 0.11 and P = 0.08, respectively). The clinical presentation and course of the patients who develop KSHV-positive solid lymphomas were also similar, except for the lack of an effusion and somewhat better survival (median 11 months vs. 3 months). However, the 3 KSHV-positive solid lymphoma patients alive without disease 11, 25, and 44 months following initial presentation were recently diagnosed patients and, unlike the other patients with KSHV-positive solid lymphomas, received anti-retroviral therapy. These findings strongly suggest that these decidedly rare KSHV-positive solid lymphomas belong to the spectrum of PEL. Therefore, we propose that the KSHV-positive solid lymphomas be designated extra-cavitary PELs.

OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma.

Abstract: OCT4 (POU5F1) is a transcription factor expressed in embryonic stem and germ cells and is involved in the regulation and maintenance of pluripotency. It has been detected in primary testicular germ cell tumors with pluripotent potential, seminoma, and embryonal carcinoma. We undertook immunohistochemical staining of OCT4 in a wide variety of primary testicular neoplasms (germ cell tumors and other tumors) to assess the specificity and usefulness of this marker as a diagnostic tool. We examined histologic sections from 91 primary testicular neoplasms, including 64 cases of mixed germ cell tumors containing embryonal carcinoma (54), seminoma (51), yolk sac tumor (38), mature teratoma (31), immature teratoma (20), and choriocarcinoma (15). In addition, we examined sections from spermatocytic seminomas (5), Leydig cell tumors (8), Sertoli cell tumors (6), unclassified sex-cord stromal tumors (4), adenomatoid tumors (2), testicular tumor of adrenogenital syndrome (1), and granulosa cell tumor (1). Each tumor was examined with hematoxylin and eosin staining and with antibodies to OCT4. In all cases of mixed germ cell tumor with components of embryonal carcinoma (54) and seminoma (51), there was greater than 90% nuclear staining of the embryonal carcinoma and seminoma tumor cells with little to no background staining. In all but 1 of these cases (embryonal carcinoma), there was strong (3+) staining intensity. The other germ cell tumor components (yolk sac tumor, mature teratoma, immature teratoma, and choriocarcinoma) showed no staining. Syncytiotrophoblast cells, which were present in 15 of the cases, were also completely negative, as were all 5 of the spermatocytic seminomas. The 22 cases of non-germ cell tumors were all immunohistochemically negative for OCT4. Fifteen of the 54 germ cell tumors containing embryonal carcinoma were also examined with antibodies to CD30. These embryonal carcinoma components were all positive for CD30 with staining of greater than 90% of the tumor cells but with variable staining intensity. We conclude that immunostaining with antibodies to OCT4 is a useful diagnostic tool in the identification of primary testicular embryonal carcinomas and "usual," but not spermatocytic, seminomas. OCT4 immunostaining has comparable sensitivity but greater consistency compared with CD30 in the diagnosis of embryonal carcinoma.

Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy.

Abstract: Histiocytic sarcoma is a rare malignant neoplasm that occurs in lymph nodes, skin, and the gastrointestinal tract. Many previously published cases were likely misdiagnosed examples of non-Hodgkin lymphoma. Only small numbers of bona fide examples exist in the world literature; cases arising primarily at extranodal sites are not well described and often seem to go unrecognized. To characterize these tumors further, 14 extranodal histiocytic sarcomas were analyzed. Hematoxylin and eosin sections were reexamined, immunohistochemistry was performed, and clinical details were obtained from referring hospitals. Eight patients were female and 6 male (median age, 55 years; range, 15-89 years). All patients presented with a solitary mass, ranging in size from 1.8 to 12 cm (median 6.8 cm). Seven tumors arose in soft tissue (6 lower limb; 1 upper limb), 5 in the gastrointestinal tract (1 involving both stomach and colon, 1 ileum, 2 rectum, 1 anus), 1 in the nasal cavity, and 1 in the lung. Three gastrointestinal tract tumors also involved regional lymph nodes, and 1 involved the liver. Most cases had infiltrative margins. The tumors were generally composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin, and large nucleoli. Binucleated cells were common, and 6 cases contained tumor giant cells. Mitoses ranged from 1 to 64 per 10 HPF (median 11 per 10 HPF). Necrosis was present in 8 cases. Nearly all tumors showed a striking inflammatory infiltrate, most often of neutrophils or lymphocytes. All cases were reactive for LCA, CD45RO, and CD68 (KP1 and PG-M1); 13 of 14 (93%) expressed CD4, 12 of 14 (86%) lysozyme, 8 of 10 (80%) CD31, 7 of 14 (50%) S-100 protein, and 5 of 14 (36%) focal CD1a. Two tumors showed weak, focal cytoplasmic positivity for CD30, and 1 for epithelial membrane antigen. The tumors were negative for ALK-1, CD21, CD35, CD3, CD20, CD34, myeloperoxidase, HMB-45, and keratins. Gastrointestinal tract cases were negative for c-kit and desmin. Six patients were treated with postoperative radiation and 7 with chemotherapy (CHOP or ProMACE-MOPP). Follow-up was available for 10 patients (median, 24 months; range, 4 months to 11 years). Two tumors recurred locally, and 5 patients developed distant spread: 3 to lymph nodes, 1 to lung, and 1 to bone. At the last follow-up, 2 patients have died of disseminated disease, 4 and 5 months following initial diagnosis. The patients who died thus far had the largest primary tumors. Histiocytic sarcoma may arise primarily in soft tissue and shows reproducible histologic features, including abundant eosinophilic cytoplasm and a prominent inflammatory infiltrate. Metastatic carcinoma, metastatic melanoma, and large cell non-Hodgkin lymphomas should be excluded by immunohistochemistry. Histiocytic sarcoma has the potential for an aggressive clinical course, most often with lymph node involvement. However, a subset of cases presenting with clinically localized disease have a favorable long-term outcome. Tumor size may be a prognostic factor.

Pigmented epithelioid melanocytoma: a low-grade melanocytic tumor with metastatic potential indistinguishable from animal-type melanoma and epithelioid blue nevus.

Abstract: In the course of a study of borderline melanocytic tumors, we observed a distinctive group of lesions characterized by features very similar to those previously described in the literature as "animal-type melanoma" and epithelioid blue nevus of Carney complex. We have designated these lesions as pigmented epithelioid melanocytoma (PEM). Herein, we present a clinical-pathologic analysis of 41 consecutive PEM from 40 patients and compare them with 11 epithelioid blue nevi from patients with Carney complex. PEM occurred in both sexes of different ethnic backgrounds, including white, Hispanic, black, Asian, and Persian. The median age of occurrence was 27 years (range 0.6-78 years). Tumors had wide distribution with extremities being the most common site. The tumors were formed by deep dermal (mean Breslow's thickness 3.3 mm) proliferation of heavily pigmented epithelioid and/or spindled melanocytes. Five lesions were part of combined nevus. Ulceration was present in 7 cases. Tumor necrosis was present in 1 case. Regional lymph nodes were sampled in 24 cases (59%). In 11 cases, lymph nodes contained metastases (46%). Liver metastases occurred in 1 case. None of the patients died of disease. Clinical follow-up of more than a year (mean 32 months, range up to 67 months) was available in 27 cases (67%). We found no histologic criteria separating metastasizing and nonmetastasizing PEM. Ulceration was the only feature more common in PEM than epithelioid blue nevi of Carney complex. Otherwise, they were histologically indistinguishable. Our data show that PEM is a unique low-grade variant of melanoma with frequent lymph node metastases but indolent clinical course. We suggest that PEM be considered as a provisional histologic entity encompassing both animal-type melanoma and epithelioid blue nevus.

Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma.

Abstract: Recent studies with cDNA microarrays showed that diffuse large B-cell lymphoma (DLBCL) cases with gene expression profiles similar to germinal center (GC) B cells had much better prognosis than DLBCL cases with gene expression profiles resembling activated B cells. The goal of the current study is to evaluate if using a panel of GC B-cell (CD10 and Bcl-6) and activation (MUM1/IRF4 and CD138) markers by immunohistochemistry defines prognosis in patients with de novo DLBCL. Immunohistochemical stains for the above markers were performed on paraffin-embedded tissues from 42 de novo DLBCL patients. Median follow-up in all patients was 41 months (range, 1-103 months) and in surviving patients was 65 months (range, 14-103 months). These cases could be classified into three expression patterns: GC B-cell pattern (pattern A) expressing CD10 and/or Bcl-6 but not activation markers; activated GC B-cell pattern (pattern B) expressing at least one of GC B-cell markers and one of activation markers; and activated non-GC B-cell pattern (pattern C) expressing MUM1/IRF4 and/or CD138 but not GC B-cell markers. Patients with pattern A had much better overall survival than those with the other two patterns (Kaplan-Meier survival analysis, P < 0.008, log rank test). Using multivariate Cox proportional hazards regression analysis, the international prognostic index scores and the expression pattern of these markers were independent prognostic indicators. Our results suggest that expression patterns of this panel of GC B-cell and activation markers by immunohistochemistry correlate with the prognosis of patients with DLBCL. Immunohistochemical analysis on paraffin-embedded tissues is more readily available than gene expression profiling by cDNA microarray and may provide similar prognostic information.

Morphologic and molecular characterization of renal cell carcinoma in children and young adults.

Abstract: A new WHO classification of renal cell carcinoma has been introduced in 2004. This classification includes the recently described renal cell carcinomas with the ASPL-TFE3 gene fusion and carcinomas with a PRCC-TFE3 gene fusion. Collectively, these tumors have been termed Xp11.2 or TFE3 translocation carcinomas, which primarily occur in children and young adults. To further study the characteristics of renal cell carcinoma in young patients and to determine their genetic background, 41 renal cell carcinomas of patients younger than 22 years were morphologically and genetically characterized. Loss of heterozygosity analysis of the von Hippel-Lindau gene region and screening for VHL gene mutations by direct sequencing were performed in 20 tumors. TFE3 protein overexpression, which correlates with the presence of a TFE3 gene fusion, was assessed by immunohistochemistry. Applying the new WHO classification for renal cell carcinoma, there were 6 clear cell (15%), 9 papillary (22%), 2 chromophobe, and 2 collecting duct carcinomas. Eight carcinomas showed translocation carcinoma morphology (20%). One carcinoma occurred 4 years after a neuroblastoma. Thirteen tumors could not be assigned to types specified by the new WHO classification: 10 were grouped as unclassified (24%), including a unique renal cell carcinoma with prominently vacuolated cytoplasm and WT1 expression. Three carcinomas occurred in combination with nephroblastoma. Molecular analysis revealed deletions at 3p25-26 in one translocation carcinoma, one chromophobe renal cell carcinoma, and one papillary renal cell carcinoma. There were no VHL mutations. Nuclear TFE3 overexpression was detected in 6 renal cell carcinomas, all of which showed areas with voluminous cytoplasm and foci of papillary architecture, consistent with a translocation carcinoma phenotype. The large proportion of TFE3 "translocation" carcinomas and "unclassified" carcinomas in the first two decades of life demonstrates that renal cell carcinomas in young patients contain genetically and phenotypically distinct tumors with further potential for novel renal cell carcinoma subtypes. The far lower frequency of clear cell carcinomas and VHL alterations compared with adults suggests that renal cell carcinomas in young patients have a unique genetic background.

c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue).

Abstract: Extragastrointestinal stromal tumor (EGIST) is a unique tumor that occurs outside the gastrointestinal tract. EGIST shows a c-kit expression and histologic appearance similar to those of gastrointestinal stromal tumor (GIST). Most GISTs have gain-of-functional mutation of the c-kit gene, and some have mutation of the platelet-derived growth factor receptor-alpha (PDGFRA) gene. However, the frequency of mutation of those genes in EGISTs remains unclear. We examined the clinicopathologic features, prognostic factors, and c-kit and PDGFRA mutation in 39 cases of EGIST. Tumors with high mitotic counts (>or=5/50 high power fields) or a high Ki-67 labeling index (>or=10%) were significantly correlated with worse prognoses. The c-kit mutation was found in the juxtamembrane domain (exon 11) and the extracellular domain (exon 9) in 12 of 29 cases (41.4%) and 2 of 29 cases (6.9%), respectively. The PDGFRA gene mutation was found at the juxtamembrane domain (exon 12) and the tyrosine kinase domain (exon 18) in one case each. The pattern of kit and PDGFRA mutation in EGIST was essentially similar to that in GIST. Our results suggest that the c-kit and PDGFRA mutations play an important role in the tumorigenesis of EGIST. High mitotic counts and a high Ki-67 labeling index may be useful for predicting the aggressive biologic behavior in EGIST. Furthermore, STI-571, targeting c-kit and PDGFR tyrosine kinase, seems to be a possible therapeutic strategy for EGISTs, especially advanced cases.

Pleomorphic liposarcoma: clinicopathologic analysis of 57 cases.

Abstract: Pleomorphic liposarcoma is an uncommon form of liposarcoma that only recently has been properly characterized. A series of 57 cases is presented. Patient age at presentation ranged from 27 to 95 years (median, 54 years), and there was a slight male predilection (male/female ratio = 1.2:1). Tumors most frequently involved the lower limb (47% of cases) or upper limb (18%). Other anatomic sites, including trunk (14%), retroperitoneum (7%), head and neck (5%), abdomen/pelvis (5%), and spermatic cord (4%), were less frequently involved. Tumor size ranged from 1.5 to 21 cm (median, 8 cm), with deep (subfascial) locations (39 cases) being more frequent than subcutaneous (11 cases) or dermal sites (5 cases). All lesions showed features of pleomorphic sarcoma and at least focally contained typical multivacuolated lipoblasts. Although there was considerable overlap, tumors fell into three broad categories: high-grade pleomorphic/spindle cell sarcoma with scattered lipoblasts or sheets of lipoblasts (60%), high-grade pleomorphic sarcoma with epithelioid areas and scattered lipoblasts (28%), and intermediate- to high-grade sarcoma predominantly resembling myxofibrosarcoma except for the presence of lipoblasts (12%). Immunohistochemistry revealed focal staining for smooth muscle actin in 13 of 29 cases (45%), S-100 protein positivity in lipoblasts in 15 of 45 cases (33%), focal staining for keratin in 6 of 28 cases (21%), including 5 of 13 (38%) with epithelioid morphology, and focal staining for desmin in 4 of 30 cases (13%). Follow-up data, available in 50 patients (88%) (median, 33 months), showed local recurrence in 34% of patients, systemic metastases in 32%, and tumor-related death in 32%. Only 2 of the 16 superficial (dermal or subcutaneous) lesions metastasized. Five-year overall, local recurrence-free, metastasis-free, and disease-free survivals were 63%, 58%, 58%, and 39%, respectively. By univariate analysis, central (nonextremity) location, deep situation, tumor size > or =10 cm, mitotic rate > or =10 per 10 HPF, necrosis, and epithelioid morphology were associated with a worse prognosis. However, by multivariate analysis, only age > or =60 years, central location, tumor size, and mitotic rate remained independent predictors for an adverse outcome. By multivariate analysis, wide local excision or amputation and postoperative radiotherapy protected against local recurrence.

Cutaneous Angiosarcoma Following Breast-conserving Surgery and Radiation: An Analysis of 27 Cases

Abstract: :Iatrogenic angiosarcomas (AS), following treatment of breast carcinomas and attributed to chronic lymphedema, were first described by Stewart and Treves. With emphasis on breast-conserving therapy combined with adjuvant radiation, a recently recognized form of cutaneous postradiation angios

Sclerosing Angiomatoid Nodular Transformation (SANT): Report of 25 Cases of a Distinctive Benign Splenic Lesion

Abstract: Twenty-five cases of a morphologically distinctive vascular lesion of the spleen are described. The patients were 17 women and 8 men, ranging in age from 22 to 74 years (mean, 48.4 years; median, 56 years). The most common presentations were incidental finding of an asymptomatic splenic mass (13 patients), abdominal pain or discomfort (6 patients), and splenomegaly (4 patients). None of the patients had evidence of recurrent disease after splenectomy. The splenic lesion was solitary, measuring 3 to 17 cm, and sharply demarcated from the surrounding parenchyma. The cut surface revealed a mass of coalescing red-brown nodules embedded in a dense fibrous stroma. All cases showed a remarkably consistent multinodular appearance at low-power examination. The individual nodules had an angiomatoid appearance, in the sense that they were composed of slit-like, round or irregular-shaped vascular spaces lined by plump endothelial cells and interspersed by a population of spindly or ovoid cells. Some of the nodules (particularly the smaller ones) were surrounded by concentric rings of collagen fibers. Numerous red blood cells were present, as well as scattered inflammatory cells. Nuclear atypia was minimal, mitotic figures were extremely rare, and necrosis was consistently absent. The internodular stroma consisted of variably myxoid to dense fibrous tissue with scattered plump myofibroblasts, plasma cells, lymphocytes, and siderophages. Immunostaining revealed 3 distinct types of vessels in the angiomatoid nodules: CD34+/CD8-/CD31+ capillaries, CD34-/CD8+/CD31+ sinusoids, and CD34-/CD8-/CD31+ small veins, recapitulating the composition of the normal splenic red pulp. These features are therefore different from those of littoral cell angioma, conventional hemangioma, and hemangioendothelioma of the spleen. We interpret these angiomatoid nodules as altered red pulp tissue that had been entrapped by a nonneoplastic stromal proliferative process. The characteristic morphologic appearance, immunophenotype, and benign clinical course suggest that this is a distinctive nonneoplastic vascular lesion of the spleen that we propose to designate as sclerosing angiomatoid nodular transformation (SANT).

High level of androgen receptor is associated with aggressive clinicopathologic features and decreased biochemical recurrence-free survival in prostate: cancer patients treated with radical prostatectomy.

Abstract: Background:Prostate cancer (PCa) is androgen dependent and is regulated by androgen/androgen receptor (AR) signaling pathway. However, the clinical significance of AR is in question. In this regard, we have correlated levels of AR expression with some well-established clinical and pathologic paramet

Cytomegalovirus infection in steroid-refractory ulcerative colitis: a case-control study.

Abstract: Cytomegalovirus (CMV) infection is reported to be a cause of steroid-refractory ulcerative colitis (UC), but the strength of this association has not been tested in a case control study. Controlled studies have also not been performed to determine the sensitivity of available immunohistochemical techniques to detect CMV in this setting. The pathology database at Stanford Hospital was searched for UC patients with a diagnosis of "severe colitis" between the years 1992 and 2002 and medical records were reviewed. Forty patients were identified with refractory UC, defined as poor response to highdose systemic steroids for >2 weeks. Another group of 40 patients with severe, but nonrefractory, UC was case-matched for age and year of biopsy. A series of 40 patients who underwent colectomy for reasons other than inflammatory bowel disease with representative sections of "normal" colon were selected as noncolitis controls. CMV inclusions were detected on hematoxylin and eosin (HE 3 had atypical inclusions; and 3 had no inclusions. CMV was not detected by H&E or IHC in 40 noncolitis controls. Of 10 steroid-refractory UC patients with CMV detected, 7 were refractory to cyclosporin or 6-mercaptopurine/azathioprine (70%) and 6 had undergone proctocolectomy (60%) prior to detection of the CMV. Two patients with recognized CMV infection were treated with gancyclovir, improved, and were able to taper off steroids and avoid proctocolectomy. This study provides evidence that unrecognized and therefore untreated CMV infection is significantly associated with steroid-refractory UC. Moreover, IHC is more sensitive than H&E for detection of CMV and should be considered as part of the routine evaluation of steroid-refractory UC patients, before proceeding with other medical or surgical therapy that may be unnecessary once the CMV is treated.

Subcutaneous, blastic natural killer (NK), NK/T-cell, and other cytotoxic lymphomas of the skin: a morphologic, immunophenotypic, and molecular study of 50 patients.

Abstract: A new group of subcutaneous, natural killer (NK), NK/T-cell, and other cytotoxic T-cell lymphomas of the skin has been recently described, and some have been included as distinct clinicopathologic entities in the classification of hematologic malignancies recently proposed by the World Health Organization. In the European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas, they would be classified either as CD30- large T-cell lymphoma, small/medium pleomorphic T-cell lymphoma, or subcutaneous T-cell lymphoma. Precise clinicopathologic and prognostic features of all of them have not yet been well characterized. We studied retrospectively 81 biopsies from 50 patients with subcutaneous, blastic natural killer (NK), NK/T-cell, or other non-mycosis fungoides cytotoxic T-cell lymphomas of the skin. Clinical, morphologic, phenotypical, and genetic features and data on Epstein-Barr virus association allowed us to classify our cases according to the following 7 categories: a) subcutaneous "panniculitis-like" T-cell lymphoma (SPTCL): 10 cases (estimated 5-year survival: 80%); b) blastic NK-cell lymphoma: 12 cases (estimated 5-year survival: 0%); c) nasal-type extranodal NK/T-cell lymphoma: 5 patients (estimated 5-year survival: 0%); d) epidermotropic CD8+ T-cell lymphoma: 5 cases (estimated 5-year survival: 0%); e) cutaneous gamma/delta T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); f) cutaneous alpha/beta pleomorphic T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); and g) cutaneous medium/large pleomorphic T-cell lymphoma, not otherwise specified: 2 cases. Our study shows that these cutaneous lymphomas can be classified according to precise diagnostic categories. With the exception of SPTCL, analysis of follow-up data from our patients showed that these groups of lymphomas are characterized by an aggressive course, regardless of the diagnostic category.

Cellular angiofibroma: clinicopathologic and immunohistochemical analysis of 51 cases.

Abstract: Cellular angiofibroma is a recently described histologically distinctive benign mesenchymal neoplasm composed of 2 principal components, the cellular spindle cell component and prominent stromal blood vessels. Cases in males have sometimes been called "angiomyofibroblastoma-like tumor." We describe a series of 51 cases of cellular angiofibroma to further characterize its clinicopathologic and immunohistochemical features. There were 26 women and 25 men, ranging in age from 22 to 78 years (mean 53.5, median 52 years). Men tended to be older than women. Tumor size ranged from 0.6 to 25.0 cm (overall median size 3.9 cm, median in women 2.7 cm, median in men 6.7 cm). Most common sites were the vulvovaginal region (22 cases) and the inguinoscrotal region (19 cases). Preoperative duration (known for 25 patients) ranged from 1 week to 5 years, with presentation as a painless mass, except for 1 case each with intermittent genital bleeding and a painful mass. Most lesions were located primarily in subcutaneous tissue. Most cases were grossly well marginated. Two cases showed foci of hemorrhage and 1 case showed foci of necrosis. Microscopically, 41 tumors were well circumscribed, and 2 tumors infiltrated into the surrounding tissue. All tumors consisted of bland, spindle-shaped cells, short bundles of wispy collagen and numerous small- to medium-sized thick-walled vessels. Intralesional fat was present in 12 cases (6 female and 6 male cases). Mild cytologic atypia (5 cases) and frequent mitoses (3 cases) were infrequent; significant nuclear atypia and abnormal mitoses were absent. By immunohistochemistry, 29 of 48 tumors (60%) expressed CD34, 10 of 48 (21%) SMA, 4 of 48 (8%) desmin, but none expressed S-100 protein. Follow-up information was available for 40 patients (range 4-168 months; mean 31.2 months) and no patient has developed recurrence or metastasis to date.

p63 expression in breast cancer: a highly sensitive and specific marker of metaplastic carcinoma.

Abstract: p63, a member of the p53 gene family, is involved in cellular differentiation and is expressed in the nuclei of myoepithelial cells of normal breast ducts and lobules. Although p63 has been reported in metaplastic carcinomas of the breast, its expression pattern in breast carcinomas and sarcomas has not been fully characterized, and its potential diagnostic utility has not been defined. In this study, we determined p63 expression in a large number of breast carcinomas, including metaplastic carcinomas, and in Phyllodes tumors and sarcomas. We examined 189 invasive breast carcinomas, including 15 metaplastic carcinomas, as well as 10 Phyllodes tumors, and 5 pure sarcomas of the breast for pattern and intensity of p63 staining using an anti-p63 antibody (clone 4A4, Neomarkers). p63 was strongly expressed in 13 of 15 metaplastic carcinomas (86.7%). p63 was positive in all the metaplastic carcinomas with spindle cell and/or squamous differentiation (12 of 12), and in 1 of 3 metaplastic carcinomas with cartilage foci. In stark contrast, only 1 of 174 (0.6%) nonmetaplastic invasive carcinomas was positive for p63. All Phyllodes tumors and sarcomas were consistently negative for p63 expression. The sensitivity and specificity of p63 as a diagnostic marker for metaplastic carcinoma was 86.7% and 99.4%, respectively. We propose the inclusion of p63 as part of the diagnostic workup of challenging spindle cell tumors of the breast as a highly specific marker for metaplastic carcinomas.