PubMed Health⌕ Search

Biomedical subjects

Andrew L Folpe

Publications and source records attributed to Andrew L Folpe.

34 records · Page 2Linked to original sources
PubMed2004

Pleomorphic hyalinizing angiectatic tumor: analysis of 41 cases supporting evolution from a distinctive precursor lesion.

The pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare, low-grade neoplasm that features atypical stromal cells containing hemosiderin, partially thrombosed ectatic vessels with circumferential hyalinization, and a variable inflammatory infiltrate. Over the years, we have occasionally observed a monomorphic partially myxoid spindle cell component (provisionally termed "early PHAT") co-existing with classic PHAT. In some instances, this monomorphic lesion occurs by itself, suggesting an early stage in the evolution of PHAT. To explore this hypothesis and to better define the long-term behavior of PHAT, we have reviewed our experience with these lesions. Forty-one cases were identified from consultation files. They occurred chiefly in adults (median 51 years, range 10-79 years) of either sex (23 female, 18 male), ranged from 0.3 to 19.7 cm (median 5.6 cm), and involved the subcutis of the ankle/foot (N = 15), leg (N = 10), thigh (N = 6), and other sites. Thirteen tumors had been present for more than 1 year prior to biopsy. Fifteen tumors consisted entirely of typical PHAT. Twelve cases conformed to "early PHAT," lacked fully developed features of PHAT, and showed instead short fascicles of hemosiderin-stippled spindled cells that infiltrated fat and surrounded congeries of small, damaged vessels. With close scrutiny, all contained rare pleomorphic cells with intranuclear pseudo-inclusions, as seen in typical PHAT. Fourteen cases contained both classic and early PHAT, in variable proportions. Follow-up was available in 18 patients (mean 84 months, median 52 months; range 13-420 months). Six of 18 patients developed recurrences, 1 with classic PHAT, 1 with mixed early-classic PHAT, and 4 with early PHAT. Following resection, 16 are disease free and 2 have persistent disease. None has developed metastasis. Based on the histologic overlap between early and classic PHAT, the presence of early PHAT at the periphery of classic PHAT, and the admixture of both patterns within the same tumor, we conclude that early PHAT represents a precursor lesion for PHAT. It appears essentially identical to the lesion termed "hemosiderotic fibrohistiocytic lipomatous lesion," supporting the notion that the latter is a neoplastic rather than a reactive lesion. PHAT should be considered mesenchymal tumors of intermediate malignancy, given their high rate of (sometimes aggressive) local recurrence.

Adolescent↗
PubMed2003

Proliferating trichilemmal tumors: clinicopathologic evaluation is a guide to biologic behavior.

BACKGROUND: Trichilemmal (pilar) cysts are common skin lesions that usually occur on the scalp of elderly women. They differentiate towards the follicular outer root sheath epithelium and show trichilemmal keratinization. Proliferating trichilemmal tumor (PTT) shows features of typical pilar cyst, but additionally shows extensive epithelial proliferation, variable cytologic atypia and mitotic activity. The malignant potential of PTT is controversial, as only a small number of histologically malignant PTTs and a smaller number of clinically malignant PTTs have been reported. METHODS: We retrieved from our archives five PTTs that deviated from ordinary PTTs with regards to either cytology or architecture. We also reviewed all previous reports of histologically malignant PTTs, with the goal of delineating criteria for the diagnosis of malignant PTTs. RESULTS: Five cases of PTT showing atypical cytoarchitectural features were retrieved from our archives and reviewed with respect to size, growth pattern, cellularity, cytologic atypia, and mitotic activity. The patients (four female, one male) ranged from 54 to 83 (mean 65) years. The tumors measured from 1 to 16 cm in diameter (mean 5 cm) and four out of five occurred on the scalp. All tumors showed at least focal areas of typical PTTs. Three cases were circumscribed but had areas of moderate to focally marked cytologic atypia. Two cases showed infiltrative growth, marked cytologic atypia and mitotic activity. Clinical follow-up was available for four of five cases and ranged from 6 to 84 (median 48) months. Follow-up showed two cases with local recurrence and one case with distant metastasis. This last patient died of disease; all other patients are disease-free. CONCLUSIONS: Review of our cases and the published literature suggests that the diagnosis of malignant PTT be given to PTT showing a combination of non-scalp location, recent rapid growth, size greater than 5 cm, infiltrative growth, and significant cytologic atypia with mitotic activity. At the present time the stratification of malignant PTT into low- and high-grade categories is not possible.

Aged↗
PubMed2003

Potential utility of uroplakin III, thrombomodulin, high molecular weight cytokeratin, and cytokeratin 20 in noninvasive, invasive, and metastatic urothelial (transitional cell) carcinomas.

The morphology of urothelial carcinomas, particularly when poorly differentiated or in metastatic sites, is not distinctive and overlaps significantly with other poorly differentiated nonurothelial carcinomas. Currently, there is no widely used single marker or panel of markers to confirm urothelial origin. We evaluated a panel consisting of antibodies to uroplakin III (UROIII), thrombomodulin (THR), high molecular weight cytokeratin (HMWCK), and cytokeratin 20 (CK20) in a wide range of urothelial tumors. Immunohistochemistry was performed on 112 paraffin-embedded urothelial neoplasms: 14 low malignant potential, 16 low-grade noninvasive, 16 high-grade noninvasive, 36 invasive, and 25 metastatic and 5 small cell carcinomas of the urinary bladder. Tissue microarray analysis was used to examine 498 tissue cores of nonurothelial tumors and normal tissue using antibodies to UROIII, THR, and HMWCK. Overall positive staining results in all urothelial tumors are as follows: UROIII, 64 of 112 (57.1%); THR, 77 of 112 (68.8%); HMWCK, 88 of 110 (80%); and CK20, 53 of 110 (48.2%). The expression of the four markers varied with tumor grade and stage. All small cell carcinomas were negative for all markers. Variant morphologic subtypes showed similar staining as conventional urothelial carcinomas. Tissue microarray analysis showed no UROIII immunoreactivity in tissue cores of nonurothelial tumors. THR was expressed by a limited number of nonurothelial cores (10 of 37 [27%] non-small cell lung carcinomas, 2 of 36 [5.6%] lymphomas). HMWCK was expressed by 43.8% of non-small cell lung carcinomas and essentially absent in other nonurothelial tumor cores. Based on the results of the study, the expression of UROIII in a tumor is essentially diagnostic of urothelial origin; however, it is expressed in only slightly more than half of urothelial tumors. The coexpression of THR, HMWCK, and CK20 strongly suggests urothelial origin. The coexpression of two of three non-UROIII markers (THR, HMWCK, CK20) suggests urothelial origin but requires clinicopathologic correlation. The results of the study indicate a role for an antibody panel that includes UROIII, THR, HMWCK, and CK20 in the diagnosis of urothelial tumors.

Biomarkers, Tumor↗
PubMed2003

Epithelioid sarcoma-like hemangioendothelioma.

We are reporting seven histologically identical cases of a distinctive, low-grade vascular tumor that closely mimics an epithelioid sarcoma because of growth in solid sheets and nests, the eosinophilia of the rounded to slightly spindled neoplastic cells, and the diffuse, strong cytokeratin expression. Termed epithelioid sarcoma-like hemangioendothelioma, all were diagnosed by the submitting pathologist or another expert consultant as epithelioid sarcoma. Although none displayed architectural evidence of vascular differentiation in the form of multicellular vascular channels, some displayed subtle cytologic features of vascular differentiation and all displayed immunohistochemical evidence of endothelial differentiation. The patients (four male; three female) ranged in age from 17 to 54 years (median 23 years). Ranging in size from 1 to 3.5 cm, they occurred in the extremities (n = 5), scalp (n = 1), and chest wall (n = 1), both in deep (n = 3) and superficial (n = 3) soft tissue or both (n = 1). The tumors were characterized by sheets, ill-defined nodules, or fascicles of deeply eosinophilic cells set within a desmoplastic stroma. Multicellular vascular channel formation and/or hemorrhage were absent in all cases. In four cases intracytoplasmic vacuolization suggestive of intracytoplasmic vascular lumen formation was noted. The typical neoplastic cell was large and rounded in shape but modulated in areas to a spindled or multipolar shape. Mitotic activity was low (<5 mitotic figures/50 high power fields), nuclear pleomorphism was mild to moderate, and necrosis was absent. The tumors were positive for cytokeratin (6 of 6), vimentin (6 of 6), CD31 (5 of 6), FLI-1 (6 of 6), but negative for CD34 (0 of 6). Within a follow-up period of 3-72 months (median 39 months), two patients experienced a local recurrence and one patient regional soft tissue metastases, but no distant ones. Two patients presented with multifocal lesions suggestive of regional metastases. Currently, two patients are alive with disease and five are disease free. Epithelioid sarcoma-like hemangioendothelioma appears to be a largely unrecognized epithelioid vascular tumor with an indolent course. Despite its similar clinical and histologic features, it differs from epithelioid sarcoma by the presence of endothelial markers and the absence to date of distant metastases. Its distinction from other epithelioid vascular lesions is discussed. We think this tumor fits best into the family of "hemangioendothelioma" or vascular lesions of intermediate malignancy.

Adolescent↗
PubMed2003

Ossifying fibromyxoid tumor of soft parts: a clinicopathologic study of 70 cases with emphasis on atypical and malignant variants.

The ossifying fibromyxoid tumor of soft parts (OFMT) is an uncommon soft tissue neoplasm of uncertain lineage. Approximately 100 cases of OFMT have been reported. Although the majority behave in a benign fashion, very rare tumors with histologic and clinical evidence of malignancy have been reported. Criteria for malignancy in OFMT have not as yet been defined. Seventy cases of OFMT were retrieved from our consultation archives and studied with respect to patient age and sex, tumor site and size, growth pattern, percentage of typical OFMT, cellularity and nuclear grade, mitotic figures (MF)/50 high power fields (HPF), atypical mitoses, necrosis, vascular invasion, and the presence of bone. Immunohistochemistry for pancytokeratin, S-100 protein, smooth muscle actin, desmin, and collagen II was performed on a subset of cases. Follow-up information was obtained from the submitting pathologists and clinicians. The Fisher exact test was used for statistical analysis. Patients (39 male, 31 female) ranged in age from 14 to 83 years (median 49 years). The tumors occurred primarily as subcutaneous or deeply seated masses in the trunk and proximal extremities and ranged from 1 to 14 cm (median 4.0 cm). The percentage of typical OFMT present in each case ranged from 0% to 100% (median 70%), and bone was present in 44 cases (63%). Mitotic activity ranged from 0 to 40 MF/50 HPF (median 2 MF/50 HPF), necrosis was present in 12 cases (17%), and vascular invasion was seen in 8 cases (11%). High cellularity or high nuclear grade was seen in 14 and 13 cases, respectively. Immunohistochemical results were as follows: S-100 protein (33 of 55, 60%), pancytokeratin (5 of 48, 10%), smooth muscle actin (2 of 44, 5%), desmin (5 of 39, 13%), and collagen II (1 of 26, 4%). Follow-up (51 cases, mean 54 months, median 36 months, range 5-151 months) showed local recurrences in nine patients and metastases in eight patients. Currently, 41 patients are disease free, 6 are alive with disease, 4 are dead of disease, and 1 died of other causes. The presence of high cellularity (p = 0.002), high nuclear grade (p = 0.001), or >2 MF/50 HPF (p = 0.004) were significantly associated with the development of metastatic disease and local recurrence. Infiltrative growth was also associated with increased risk of local recurrence (p = 0.03). We conclude that the histologic spectrum of OFMT is broader than previously appreciated, as many clinically benign cases display moderate cellularity, nuclear enlargement, or have identifiable mitotic figures. Our results strongly suggest that OFMT with 1) high nuclear grade or 2) high cellularity and mitotic activity of >2 MF/50 HPF should be regarded as sarcomas with significant potential for metastasis and untoward outcome ("malignant OFMT"). The remainder can be considered within the spectrum of OFMT, recognizing that even these lesions possess a risk, albeit very low, of metastasis. Consequently, OFMT should be considered tumors of intermediate malignancy. Their line of differentiation remains unclear, although we suggest they may belong to the category of translocation-associated sarcomas, not all of which recapitulate a normal line of differentiation.

Adolescent↗
PubMed2003

Immunoprofile of ovarian tumors with putative transitional cell (urothelial) differentiation using novel urothelial markers: histogenetic and diagnostic implications.

Ovarian tumors containing cells with transitional cell morphology are recognized in the 1999 World Health Organization classification of ovarian tumors and include benign Brenner tumor, borderline and malignant Brenner tumor, and transitional cell carcinoma. Recent immunohistochemical investigations have reached conflicting conclusions regarding true urothelial differentiation in ovarian Brenner tumors. We evaluated a panel consisting of antibodies to uroplakin III (UROIII), thrombomodulin (THR), cytokeratin 7 (CK7), cytokeratin 20 (CK20), and Wilms' tumor protein (WT1) to study urothelial differentiation in ovarian transitional cell tumors. Additionally, we compared the immunohistochemical profile of transitional cell carcinoma of the ovary (TCC-O) with that of transitional cell carcinoma of the bladder (TCC-B), to ascertain if immunohistochemistry may aid in distinguishing primary from metastatic TCC-O. Seventeen benign Brenner tumors and 17 TCC-O were stained with antibodies to UROIII, THR, CK7, CK20, and WT1. Additionally, 6 Brenner tumors of borderline malignancy were stained with antibodies to UROIII, THR, CK7, and CK20. The immunohistochemical results were compared with those of 30 cases of noninvasive TCC-B (low malignant potential n=14, low grade n=16) and 36 cases of invasive TCC-B stained with a similar panel of antibodies as part of another study. Twenty-one nontransitional cell ovarian carcinomas (9 serous, 4 clear cell, 5 endometrioid, 2 mixed endometrioid/serous, and 1 mucinous) were used as controls. Most Brenner tumors showed positivity with UROIII (82%) and THR (76%), supporting true urothelial differentiation in these tumors. Although TCC-O has considerable morphologic overlap with TCC-B, they had only partial immunophenotypic overlap. TCC-O rarely expressed UROIII (6%) and THR (18%) and none expressed CK20. In contrast, nearly 40% of invasive TCC-B expressed UROIII, 61% expressed THR, and 50% expressed CK20. Nearly 82% of TCC-O expressed WT1, which was negative in all TCC-B. Our results may have diagnostic value in distinguishing TCC-O (CK20-, UROIII-/+, WT1+) and invasive TCC-B (CK20+, UROIII+/-, WT1-) metastatic to the ovary. They also indicate that the morphologic similarity between TCC-O and TCC-B does not indicate any histogenic similarity and, as others have noted, TCC-O is a variant morphology in the spectrum of surface epithelial carcinomas.

Biomarkers, Tumor↗
PubMed2003

The diagnostic value of hepatocyte paraffin antibody 1 in differentiating hepatocellular neoplasms from nonhepatic tumors: a review.

Hepatocyte paraffin-1 (HepPar-1) is a recently developed monoclonal antibody that appears to identify an antigen unique to hepatocellular mitochondria. This article reviews the use of this new antibody in the differential diagnosis of primary hepatocellular neoplasms, cholangiocarcinomas, and carcinomas metastatic to the liver. Hepatocyte paraffin-1 appears to be the most sensitive and specific positive marker of hepatocellular differentiation, but like any immunohistochemical marker, should be interpreted only in the context of the overall clinicopathologic picture and as part of a panel of antibodies.

Antibodies, Monoclonal↗
PubMed2003

Protein gene product 9.5 (PGP 9.5) is not a specific marker of neural and nerve sheath tumors: an immunohistochemical study of 95 mesenchymal neoplasms.

In non-neoplastic tissues, the expression of protein gene product 9.5 (PGP 9.5), a member of the ubiquitin hydrolase family of proteins, is confined to neural and neuroendocrine cells. Although it has been claimed that PGP 9.5 is a specific marker of neural and/or nerve sheath differentiation in human tumors, careful review of the literature suggests that relatively few nonneural or nerve sheath tumors have been studied. Prompted by our recent observation of a PGP 9.5-positive malignant fibrous histiocytoma, we undertook a study of PGP 9.5 expression in a large group of well-characterized mesenchymal neoplasms. Sections from 95 mesenchymal tumors were retrieved from our archives and immunostained for PGP 9.5 using standard avidin-biotin complex technique and heat-induced epitope retrieval. Scoring was as follows: negative, 1+ (<10-25% of cells), 2+ (25-50% of cells), and 3+ (>50% of cells). Normal nerves and fibrous tissue were internal positive and negative controls, respectively. Positive immunostaining was seen in 80/95 (84%) of cases. Positive results by tumor subtype were as follows: (1) nerve sheath tumors: malignant peripheral nerve sheath tumor (7/10), neurofibromas (10/10), and perineuriomas (3/3); (2) (Myo) fibroblastic tumors: malignant fibrous histiocytoma (18/20), low-grade fibromyxoid sarcomas (8/9), fibromatoses (7/7), and desmoplastic fibroblastomas (2/2); (3) vascular tumors: angiosarcomas (4/4), hemangioendotheliomas (3/5), and hemangiomas (3/4); and (4) other non-nerve sheath tumors: pleomorphic liposarcoma (4/4), dermatofibrosarcoma protuberans (2/5), rhabdomyosarcomas (2/2), synovial sarcomas (8/8), melanomas (1/2). All positive cases were 2-3+ except 6 malignant peripheral nerve sheath tumor, 1 neurofibroma, 3 malignant fibrous histiocytoma, 2 low-grade fibromyxoid sarcoma, and 1 dermatofibrosarcoma protuberans. Positive staining was seen in normal smooth muscle and germinal centers in addition to nerves. We conclude that in this, the largest study to date of PGP 9.5 expression in mesenchymal neoplasms, we have found strong (2-3+) expression in the vast majority of nonneural or nerve sheath neoplasms studied. Although PGP 9.5 is a sensitive neural/nerve sheath marker, it is essentially totally nonspecific for diagnostic purposes. It is possible that our findings reflect cross-reactivity of the 13C4 clone with epitopes present on other ubiquitin hydrolases. Alternatively, PGP 9.5 expression may be aberrantly up-regulated in a variety of mesenchymal neoplasms.

Biomarkers, Tumor↗
PubMed2002

Primary Ewing's sarcoma/primitive neuroectodermal tumor of the kidney: a clinicopathologic and immunohistochemical analysis of 11 cases.

Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) is an extraordinarily rare primary tumor in the kidney and can be mistaken for a variety of other round cell tumors, including blastema-predominant Wilms' tumor (WT). Approximately 90% of ES/PNET have a specific t(11;22), which results in a chimeric EWS-FLI-1 protein. Immunohistochemistry for the carboxy-terminus of FLI-1 is sensitive and highly specific for the diagnosis of ES/PNET. WT-1, the WT-associated tumor suppressor gene, is overexpressed in WT but not in ES/PNET. No study has examined FLI-1 or WT-1 expression in renal ES/PNET. The clinicopathologic features of 11 renal ES/PNET were studied along with immunohistochemistry for cytokeratin, desmin, CD99, FLI-1, and WT-1. WT were also immunostained for CD99 (5 cases), FLI-1 (10 cases), and WT-1 (9 cases). The patients (6 men, 5 women) ranged from 18 to 49 years of age (mean, 34 yr). The mean tumor size was 11.8 +/- 3.8 cm (mean +/- standard deviation). Presenting symptoms included abdominal/flank pain and/or hematuria. Grossly, all tumors showed necrosis and hemorrhage, and 4 had cystic change. Microscopically, all tumors showed vaguely lobular growth, primitive round cells, and variable rosette formation. Epithelial, myogenous, or cartilaginous differentiation was not seen. Immunohistochemical results on the renal ES/PNET were cytokeratin (2/8 focal), desmin (0/9), CD99 (8/8), FLI-1 (5/8), and WT-1 (0/8). In comparison, the WT only rarely expressed CD99 (1/5) and did not express FLI-1 (0/10), but were usually WT-1-positive (7/9). Follow-up on 8 cases (mean, 28 mo; range, 6-64 mo) showed 4 lung and pleural metastases, 1 bone metastasis, liver metastasis, 2 local recurrences, and 5 deaths from disease (median time to death, 16.8 mo). No case had distant metastatic disease at presentation. Adjuvant therapy included chemotherapy (8 cases), radiation (3 cases), and bone marrow transplantation (1 case). Our study affirms a unique proclivity of renal ES/PNET for young adults and that it is a highly aggressive neoplasm, with rapid death in many cases, usually after the development of treatment-resistant lung metastases. These tumors must be distinguished from blastema-predominant WT and other primitive renal tumors that require different therapy. FLI-1 and WT-1 immunohistochemistry may be valuable in this differential diagnosis, given the known immunophenotypic overlap between ES/PNET and blastema-predominant WT with regard to CD99, cytokeratin, and desmin. The accurate distinction between these two entities has clear prognostic and therapeutic implications.

12E7 Antigen↗
PubMed2002

Lipoleiomyosarcoma (well-differentiated liposarcoma with leiomyosarcomatous differentiation): a clinicopathologic study of nine cases including one with dedifferentiation.

Leiomyosarcomatous (LMS) differentiation is a rare event in liposarcoma (LPS) and may consist of either well-differentiated liposarcoma (WDL) with an intrinsic smooth muscle component, so-called "lipoleiomyosarcoma," (L-LMS) or dedifferentiated liposarcoma having smooth muscle differentiation in the dedifferentiated zones. The latter are high-grade sarcomas, whereas the behavior of the former group is uncertain. Specifically, it is not clear whether the presence of LMS negatively affects the prognosis. We present our experience with nine cases, the largest to date. The patients (seven male, two female) ranged in age from 42 to 65 years (mean 54 years). The tumors were usually large (2 to >40 cm [mean 17 cm]) tumors in the retroperitoneum (two cases), paratesticular-inguinal region (three cases), mediastinum (one case), lung (one case), abdomen (one case), and popliteal fossa (one case). The nine cases qualified as L-LMS and showed typical WDL with a multifocal, gradual transition into smooth muscle areas. The latter areas accounted for a variable portion of the lesions (range 5-90%) and were of low cellularity, mild to moderate nuclear atypia, and low mitotic activity. These areas seemed to arise from or blend with the smooth muscle in the walls of large vessels within the tumor. One case showed areas of dedifferentiation consisting of actin and desmin-negative, high-grade sarcoma. Follow-up in seven cases (range 26-312 months; mean 119 months) showed multiple local recurrences in seven patients and no metastases. Three patients are currently without evidence of disease (follow-up duration 26-312 months; mean 144 months) and four patients are alive with progressive disease (follow-up duration 60-132 months; mean 99 months). Our study suggests that L-LMS is a dual lineage sarcoma as evidenced by the fact that the smooth muscle component is often multifocal, not necessarily found in close association with the atypical changes in fat, and seemingly originates from atypical ("in situ") changes in the vessel wall. The LMS component, which is typically low grade, does not adversely affect the overall behavior of the tumor, which is similar to that of conventional WDL. LMS in L-LMS should not be misconstrued as evidence of low-grade dedifferentiation, a phenomenon that identifies a more unstable and potentially metastasizing lesion.

Adult↗
PubMed2002

Clear cell myomelanocytic tumor of the thigh: report of a unique case.

The clear cell myomelanocytic tumor (CCMMT) is a recently reported and very rare member of the perivascular epithelioid cell family of tumors (PEComa). All CCMMTs reported to date have occurred in or immediately adjacent to the falciform ligament/ligamentum teres. We report a case of CCMMT that occurred in the right thigh of a 43-year-old woman. Histologic examination showed the classic features of CCMMT, and immunohistochemical studies confirmed co-expression of smooth muscle actin, HMB-45, and microphthalmia transcription factor.

Actins↗
PubMed2002

Sclerosing rhabdomyosarcoma in adults: report of four cases of a hyalinizing, matrix-rich variant of rhabdomyosarcoma that may be confused with osteosarcoma, chondrosarcoma, or angiosarcoma.

Rhabdomyosarcomas (RMSs) are classified into embryonal (ERMS), alveolar (ARMS), and pleomorphic (PRMS) subtypes. ERMS, including botryoid variants, typically occurs in young children, ARMS typically occurs in older children and young adults, and PRMS occurs in older adults. Although ARMSs show thin fibrous bands separating nests of cells, abundant extracellular matrix production is rare in RMS. In the course of reviewing hyalinizing sarcomas we discovered a distinctive RMS in adults that closely mimicked osteosarcoma or chondrosarcoma because of the extensive matrix production. Four RMSs with hyalinized matrix were retrieved from our files. These cases were evaluated with respect to patient age and sex, tumor site and size, growth pattern, nuclear grade, cellularity, mitotic figures/20 high power fields, vascular invasion, necrosis, the presence of rhabdomyoblasts, multinucleated cells, and alveolar growth pattern. Immunohistochemistry for desmin, myogenin, MyoD1, actin, cytokeratin, S-100 protein, collagen II, and CD99 was performed. Reverse transcriptase polymerase chain reaction for the ARMS-associated PAX3/FKHR and PAX7/PKHF was also performed on three cases. The cases involved the forearm, hand, orbit, and nasopharynx of a 40-year-old woman, a 50-year-old man, an 18-year-old man, and a 21-year-old man, respectively. The tumors ranged from 3.7 to 8 cm and consisted of lobules and infiltrating cords of small round malignant cells embedded in a densely hyalinized matrix having both a chondroid and osteoid-like appearance. No definite lacunae or matrix calcification was present. An alveolar pattern was only present focally, and tumor giant cells were not present. One case had a single focus of rhabdomyoblastic differentiation with strap cells. Mitotic activity was >20 mitotic figures/20 high power fields in three of four cases. Immunohistochemically, one case strongly expressed desmin, whereas three cases expressed it focally, with a dot-like pattern. Myogenin was only focally positive, but MyoD1 was present in nearly every cell of each case. Two cases expressed actin and one expressed CD99. No case expressed cytokeratin, S-100 protein, or collagen II. Only one case contained adequate RNA for reverse transcriptase polymerase chain reaction, and this case was negative for the ARMS-associated gene fusions. Follow-up showed one patient to be dead of metastatic disease at 60 months despite intensive therapy, another patient to be disease free at 26 months, and the third patient to be disease free at 5 months. The fourth case is recent. These cases are a distinctive-appearing rhabdomyosarcoma easily mistaken for variants of chondrosarcoma, osteosarcoma, or even sclerosing epithelioid fibrosarcoma because of their hyalinizing appearance compounded by their typically focal and dot-like desmin expression. These four cases are essentially identical to the three unusual RMSs recently reported by Mentzel and Katenkamp as "sclerosing, pseudovascular rhabdomyosarcoma in adults." Although the focal alveolar architecture and the primitive cytologic appearance of these hyalinizing RMS suggest a relationship with ARMS, the presence of abundant strap cells in one case, the predominant expression of MyoD1 rather than myogenin, and the absence of ARMS-associated fusions genes point more strongly toward a variant of ERMS. However, the late adult age in two cases is unusual for both EMRS and ARMS, suggesting that sclerosing RMS may prove to be a distinct subtype of RMS. Study of additional cases will be necessary to more fully elucidate its place among RMS and its prognostic significance.

Adolescent↗
PubMed2002

Expression of claudin-1, a recently described tight junction-associated protein, distinguishes soft tissue perineurioma from potential mimics.

Perineuriomas are rare benign soft tissue tumors having an immunophenotype paralleling the normal perineurial cell [S-100 protein negative and epithelial membrane antigen (EMA) positive]. Because EMA expression in perineuriomas may be focal and/or faint, there is continued interest in the development of new markers of perineurial differentiation. Perineurial cells differ from almost all other mesenchymal cell types by virtue of their formation of tight junctions. In the course of evaluating a group of novel tight junction-associated proteins, we noted high levels of expression of claudin-1 by normal perineurial cells and have systematically extended these observations to perineuriomas. Twelve EMA-positive/S-100-negative perineuriomas were retrieved from our consultation archives and compared with 39 tumors in the differential diagnosis of perineurioma (seven dermatofibrosarcoma protuberans, eight low-grade fibromyxoid sarcomas, three desmoplastic fibroblastomas, seven fibromatoses, nine neurofibromas, and five schwannomas). All cases were immunostained for claudin-1 using standard avidin-biotin technique. Cases were scored as 3+ (>50% positive cells), 2+ (25-50% positive cells), and 1+ (5-24% positive cells). In all cases positive internal controls in the form of epithelium, normal perineurium, or endothelial cells were present. Positive staining for claudin-1 was visualized in a distinctly particulate pattern along the cell membrane. Cytoplasmic staining was infrequent and was not scored as positive. Claudin-1 expression was present in 11 of 12 (92%) perineuriomas studied (seven at 3+, three at 2+, and one at 1+). In all but two cases, the degree of claudin expression was equal to or greater than the corresponding EMA immunostain. Claudin-1 expression was not noted in any cases of dermatofibrosarcoma protuberans, low-grade fibromyxoid sarcoma, desmoplastic fibroblastoma, or fibromatosis. Six of nine cases of neurofibroma contained a significant number of claudin-1-positive cells that were thought to be perineurial in origin, based on the staining of long, delicate cytoplasmic processes. One of four schwannomas contained a subpopulation of perivascular, dendritic, claudin-1-positive cells of presumed perineurial lineage. This is the first study to document expression of claudin-1 in perineurial cells and suggests a role for claudin-1 immunohistochemistry in the diagnosis of perineuriomas. Although claudin-1 should not replace EMA in the diagnosis of perineurioma, we think that it may play a valuable adjunctive role in difficult cases. In particular, claudin-1 is often a more robust marker than EMA in a given perineurioma. Claudin-1 is not expressed within the lesional cells of the mesenchymal tumors that enter into the differential diagnosis of perineurioma.

Biomarkers, Tumor↗
PubMed2002

MyoD1 and myogenin expression in human neoplasia: a review and update.

The MyoD1 family of myogenic nuclear regulatory proteins includes MyoD1/myf3 and myogenin/myf4. These genes and their proteins are critical for skeletal muscle development. Antibodies to MyoD1 and myogenin are relatively recent additions to the armamentarium of the surgical pathologist. This article reviews the biology of the myogenic nuclear regulatory proteins and their use in the diagnosis of rhabdomyosarcoma. Special attention is given to technical and interpretative issues critical to the use of these antibodies in diagnostic pathology.

Biomarkers↗
PubMed2002

C-kit expression distinguishes salivary gland adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma.

Adenoid cystic carcinoma (ACC) is characterized by persistent, relentless growth and a high rate of eventual metastasis. In contrast, polymorphous low-grade adenocarcinoma (PLGA) has a much lower risk of recurrence and rarely metastasizes. The histologic patterns of these two neoplasms can be similar. Expression of c-kit, a transmembrane receptor tyrosine kinase, has recently been reported to be expressed in ACC but not PLGA. Expression of galectin-3, a nonintegrin beta-galactosidase-binding lectin, has been reported to be significant in PLGA and decreased in ACC.Formalin-fixed paraffin-embedded tissue from 9 ACC and 14 PLGA were immunostained for c-kit and galectin-3. Cases were scored as 1+ (5-25% positive), 2+ (26-50% positive), or 3+ (>50% positive). C-kit was expressed by 100% of ACC (3+: 7 cases; 2+: 1 case; 1+: 1 case) and by 57% of PLGA (2+: 2 cases; 1+: 6 cases). In all but one ACC, c-kit expression was confined to the inner cell layer. C-kit expression was also noted in the intercalated duct epithelium of the salivary glands and the acinar cells of the lacrimal gland. Galectin-3 was expressed in 8 of 9 cases of ACC and 14 of 14 cases of PLGA. The results of this, the first study to compare c-kit and galectin-3 expression in ACC and PLGA, suggest that c-kit expression characterizes ACC, but not PLGA. Galectin-3 immunohistochemistry does not have a role in the differentiation of ACC and PLGA. C-kit immunostaining may be a valuable adjunctive tool for this differential diagnosis, particularly in the setting of a limited biopsy. Our finding of different patterns of c-kit expression in tubular and solid variants of ACC supports the concept of solid variant ACC as a high-grade tumor, with progression toward an entirely "inner cell" phenotype.

Adenocarcinoma↗