Biomedical subjects

M Miettinen

Publications and source records attributed to M Miettinen.

At least 19 recordsLinked to original sources

PubMed1999

Nuchal-type fibroma: a clinicopathologic study of 52 cases.

BACKGROUND: Nuchal-type fibroma (NTF) usually arises in the posterior aspect of the neck. Previously published reports describe only 11 cases and provide limited clinicopathologic information. METHODS: Fifty-two examples of NTF from 50 patients were analyzed from the files of the Soft Tissue Registries of the Armed Forces Institute of Pathology in Washington, DC, and the Faculty Hospital in Pilsen, Czech Republic. RESULTS: The age of the patients ranged from 3 to 74 years (mean, 40 years). There were 41 males and 9 females. Thirty-six NTFs were located in the posterior neck region and 16 were from extranuchal sites. Two patients had had lesions excised from both a nuchal and an extranuchal location. The mean greatest tumor dimension was 3.2 cm. Microscopically, all examples had a superficial (subcutaneous and sometimes dermal) component and consisted of paucicellular, thick bundles of lobulated collagen fibers with inconspicuous fibroblasts. Entrapped adipose tissue and traumatic neuromalike nerve proliferations were typically present. Skeletal muscle infiltration was also seen in a minority of cases. Eleven of 25 patients (44%) for whom clinical information was available reportedly had diabetes. Gardner's syndrome was documented in one patient and was possibly present in two additional individuals. During follow-up, five patients had local recurrences, but none of the recurrences were destructive and all were ultimately controlled by local reexcision. CONCLUSIONS: NTF is a rare, tumorlike accumulation of collagen that often affects the posterior neck region but can also occur in a number of other sites. The process has a strong association with diabetes and also appears to be linked to Gardner's syndrome. Local recurrence probably reflects the persistence of local or systemic factors related to its pathogenesis.

Adolescent↗

PubMed1999

Distinct patterns and kinetics of chemokine production regulate dendritic cell function.

Dendritic cells (DC) have been showed to both produce and respond to chemokines. To understand how this may impact on DC function, we analyzed the kinetics of chemokine production and responsiveness during DC maturation. After stimulation with LPS, TNF-alpha or CD40 ligand, the inflammatory chemokines MIP-1alpha, MIP-1beta and IL-8 were produced rapidly and at high levels, but only for a few hours, while RANTES and MCP-1 were produced in a sustained fashion. The constitutive chemokines TARC, MDC and PARC were expressed in immature DC and were up-regulated following maturation, while ELC was produced only at late time points. Activated macrophages produced a similar spectrum of chemokines, but did not produce TARC and ELC. In maturing DC chemokine production had different impact on chemokine receptor function. While CCR1 and CCR5 were down-regulated by endogenous or exogenous chemokines, CCR7 levels gradually increased in maturing DC and showed a striking resistance to ligand-induced down-regulation, explaining how DC can sustain the response to SLC and ELC throughout the maturation process. The time-ordered production of inflammatory and constitutive chemokines provides DC with the capacity to self-regulate their migratory behavior as well as to recruit other cells for the afferent and efferent limb of the immune response.

Chemokines↗

PubMed1999

Absence of Kaposi's sarcoma-associated virus (human herpesvirus-8) sequences in angiosarcoma.

Kaposi's sarcoma-associated virus (human herpesvirus-8 [HHV8]) sequences have been identified in both AIDS-associated and AIDS-non-associated Kaposi's sarcoma, but data relating to the detection of HHV8 sequences in angiosarcoma are variable. One study showed HHV8 sequences in 29% (7/24) of angiosarcomas, but others have not confirmed these results. We evaluated 33 angiosarcomas for HHV8 sequences to determine the frequency of this virus in angiosarcomas and its possible pathogenetic significance. Five cases of Kaposi's sarcoma from HIV-positive patients were used as positive controls. Five additional cases of Kaposi's sarcoma collected approximately 40-50 years ago were also analysed, and three were HHV8 positive. None of the angiosarcomas revealed HHV8 sequences after the standard 35 cycles of PCR. In 6 cases, nested PCR revealed the presence of HHV8 sequences. These results were not reproducible when outer primers (based on sequences outside of the earlier PCR products) were used for amplification. This suggests that the HHV8 sequences detected in 6 cases represent a low level of contamination. In contrast, HHV8 sequences were found in all Kaposi's sarcomas with well-preserved DNA after standard 35-cycle PCR amplification. These findings confirm a close association between Kaposi's sarcoma and HHV8 infection and suggest that HHV8 is not involved in the pathogenesis of angiosarcoma.

Adult↗

PubMed1999

Myoepitheliomas of the skin and soft tissues. Report of 12 cases.

We describe 12 cutaneous and soft tissue myoepitheliomas, most of them in elderly patients. Morphologically the cutaneous and soft tissue myoepitheliomas revealed the same spectrum as their salivary gland counterparts. They were composed of a mixture of spindle, epithelioid and clear myoepithelial cells. Immunohistochemically they were positive to keratins and S-100 protein and reacted inconsistently with antibodies to smooth muscle actin. Morphologically they lacked any folliculo-sebaceous or apocrine differentiation. We believe that they are related to the eccrine type of cutaneous mixed tumours. Most cases had a benign behaviour, but 1 tumour metastasized, and the patient died of the tumour. Myoepitheliomas of soft tissues should be distinguished from other neoplasms with epithelial differentiation and from ossifying fibromyxoid tumour of soft parts, parachordoma and extraskeletal myxoid chondrosarcoma.

Adult↗

PubMed1999

Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas.

Gastrointestinal stromal tumors (GISTs) comprise the largest subset of mesenchymal tumors of the gastrointestinal tract. These neoplasms differ histologically and immunohistochemically from typical leiomyomas and leiomyosarcomas. Most GISTs express CD34 and CD117 (c-kit protein) but not desmin. Recently, gain-of-function mutations of c-kit proto-oncogene have been shown in five solitary GISTs and in tumors and leukocytes from a family with multiple GISTs. An in-frame deletion or a point mutation in exon 11 of c-kit was detected in these cases. Stable transfection of the mutant c-kit complementary DNA was also shown to induce malignant transformation of murine lymphoid cells, suggesting that the c-kit mutations contribute to tumor development. In this study, we evaluated 43 GISTs and 14 smooth muscle tumors for mutations in the exon 11 of c-kit by a PCR-assay. Half of the malignant GISTs (12/24) and only one benign GIST (1/19) revealed mutant bands. No mutant bands were found in 3 leiomyomas and 11 leiomyosarcomas. Sequence analysis confirmed the presence of an in-frame deletion of 3-21 bp in all 13 GISTs with mutant bands. Wild-type bands from 8 malignant and 11 benign GISTs and 7 smooth muscle tumors without mutant bands were cloned and sequenced. Additional mutations were found in 3 malignant and 2 benign GISTs. There were no mutations in 3 leiomyomas and 4 leiomyosarcomas. The mutation status of exon 11 did not correlate with immunohistochemically detectable expression of the CD117, as virtually all GISTs with or without such mutations showed CD117 immunoreactivity. The c-kit mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs. The conservation of the c-kit mutation pattern, observed in consecutive lesions from the same patients, suggests that these mutations might be useful tumor markers in monitoring recurrence or minimal residual disease.

Adult↗

PubMed1999

Osteocalcin and osteonectin immunoreactivity in extraskeletal osteosarcoma: a study of 28 cases.

Extraskeletal osteosarcoma (EOSA), a rare malignant soft tissue tumor, is by definition unattached to the skeleton and composed of malignant cells of osteoblastic phenotype which produce osseous matrix (ie, neoplastic bone). Because of its location, it can mimic other soft tissue tumors, and its matrix can be mistaken for hyalinized collagen. Antiosteocalcin (OC) and antiosteonectin (ON), antibodies against two abundant human bone proteins, are explored in the diagnosis of EOSA. Twenty-eight cases coded as EOSA (n=24) or probable EOSA (n = 4) were identified from the Soft Tissue Registry of the Armed Forces Institute of Pathology (Washington DC). All cases had paraffin blocks available for immunohistochemistry. OC and ON (Biodesign International, Kennebunk, ME, clones OC1 and OST1) immunostaining for tumor cells and matrix was graded on a four-tiered grading system: 1 = focal (< 50%) weak staining; 2 = focal strong staining; 3 = diffuse (> or = 50%) weak staining; and 4 = diffuse strong staining. Patient ages ranged from 9 to 80 years, with a mean age of 57 years. There were 9 female patients and 19 male patients. The tumor sizes ranged from 1.5 to 15 centimeters, with a mean size of 5.8 centimeters. Locations included the lower extremity (n=14), trunk (n=9), upper extremity (n=4), and head and neck (n=1). Subtypes included 12 osteoblastic, 4 fibroblastic, 2 chondroblastic, 2 well differentiated, 1 telangiectatic, 1 small cell, and 6 giant cell rich EOSAs; the latter resembled giant cell rich malignant fibrous histiocytomas with neoplastic bone formation. All tumors had both neoplastic cells and bony tumor matrix to evaluate. OC was 82% sensitive for EOSA neoplastic cells (1 to 4+), with immunostaining of neoplastic cells away from bone in 91% of cases, and 75% for bony tumor matrix (2 to 4+). ON was 93% sensitive for EOSA neoplastic cells (2 to 4+), yet only 39% for bony tumor matrix (1 to 4+). In 100% giant cell rich EOSA, neoplastic cells were positive for OC and ON (2 to 4+). OC showed 100% specificity for osteoblasts as it was nonreactive in all nonbone cells. ON was not specific for osteoblasts but consistently immunostained other cell types in our EOSA tumors: fibroblasts (100%), pericytes (96%), endothelial cells (92%), chondrocytes (5/5), basal layer of skin epithelium (1/4), nerves (2/2), and osteoclastic giant cells (64%). ON also stained several other cell types in normal and neoplastic tissues in our battery of preliminary stainings; OC was negative in all nonosteoblastic tissues and tumors. Both OC and ON were specific for osteoid matrix as they were nonreactive in both collagen and cartilage matrix. OC is a sensitive and specific marker for bone cells and would be helpful in identifying EOSA, even in the absence of neoplastic bone on small biopsies. ON and OC (more sensitive) will both distinguish malignant bone from collagen and cartilage matrix, essential to the diagnosis of EOSA.

Adolescent↗

PubMed1999

Sources of Listeria monocytogenes contamination in a cold-smoked rainbow trout processing plant detected by pulsed-field gel electrophoresis typing.

Sites of Listeria monocytogenes contamination in a cold-smoked rainbow trout (Oncorhynchus mykiss) processing plant were detected by sampling the production line, environment, and fish at different production stages. Two lots were monitored. The frequency of raw fish samples containing L. monocytogenes was low. During processing, the frequency of fish contaminated with L. monocytogenes clearly rose after brining, and the most contaminated sites of the processing plant were the brining and postbrining areas. A total of 303 isolates from the raw fish, product, and the environment were characterized by pulsed-field gel electrophoresis (PFGE). PFGE yielded nine pulsotypes, which formed four clusters. The predominating L. monocytogenes pulsotypes of the final product were associated with brining and slicing, whereas contaminants of raw fish were not detected in the final product. Air-mediated contamination in the plant could not be proved. In accordance with these results, an L. monocytogenes eradication program was planned. The use of hot steam, hot air, and hot water seemed to be useful in eliminating L. monocytogenes. None of the control samples taken in the 5 months after the eradication program was implemented contained L. monocytogenes.

Animals↗

PubMed1998

Epithelial expression of glycodelin in biphasic synovial sarcomas.

Glycodelin is a 28 kDa glycoprotein of the lipocalin family that was previously considered to be specific for the reproductive tract. Glycodelin is found in the secretory glandular epithelium of endometrium and in seminal vesicles. Given the cyclic differentiation of normal endometrial epithelium, we studied by immunohistochemistry a possible expression of glycodelin in other tissues displaying stroma-to-epithelium maturation. We report here that 11/11 biphasic synovial sarcomas expressed glycodelin in the cells exhibiting epithelial or glandular differentiation while the sarcomatous spindle cells remained negative. Glycodelin was also found in secreted material in the lumina of the gland-like structures. In only 1 of the 7 monophasic synovial sarcomas studied, focal glycodelin reactivity was seen in some flattened spindle cells. The expression of glycodelin in biphasic synovial sarcoma tissue was further verified by the demonstration of glycodelin mRNA by reverse transcriptase-polymerase chain reaction. Considering the monoclonal origin of synovial sarcomas, our findings raise the intriguing possibility that activation of expression of the glycodelin gene is involved in the molecular regulation of mesenchyme-to-epithelium differentiation.

Epithelium↗

PubMed1998

Follicular dendritic cell sarcoma and interdigitating reticulum cell sarcoma: a review.

Neoplasms of reticular dendritic origin are extremely rare and include the follicular dendritic cell sarcoma (FDCS) and the interdigitating reticulum (or dendritic) cell sarcoma (IDCS). In this article, we review the literature pertaining to the two diseases and describe clinical observations and salient pathologic features, including information provided by authors of FDCS and IDDCS reports. We performed a computerized database search for published articles regarding FDCS and IDDCS. The articles were evaluated critically by the authors. Simple descriptive statistics were used to analyze the data. There are 51 cases of FDCS and 21 cases of IDDCS that are well documented in the literature. The pathologic diagnosis of FDCS and IDDCS is often challenging and requires morphologic, immunophenotypic, cytochemical, and electron-microscopic analysis. Patients with FDCS usually present with cervical or axillary lymphadenopathy, but extranodal disease has been described. In at least some patients, preexisting Castleman's disease has been recognized. Resected localized disease may be prevented from recurrence by consolidative radiotherapy. Chemotherapy regimens have shown nondurable antitumor activity in FDCS. Patients with IDDCS usually present with lymphadenopathy. The clinical course of IDDCS has been variable, but it seems to be more aggressive than that of FDCS. Variable degrees of remission may be achieved with chemotherapy. FDCS and IDDCS are rare neoplasms that may pose difficulty in pathologic diagnosis. IDDCS seems to display a more aggressive behavior than FDCS. Patients with IDDCS and FDCS can eventually die of disease progression. The role of chemotherapy and radiotherapy is not clearly defined.

Dendritic Cells↗

PubMed1998

Immunocytochemical evaluation of HBME-1, CA 19-9, and CD-15 (Leu-M1) in fine-needle aspirates of thyroid nodules.

Overlapping morphologic patterns that may be observed in goiter, follicular adenoma, and papillary carcinoma can limit the cytologic evaluation of the thyroid gland. In an attempt to develop a useful adjunctive test, the immunocytochemical reactivity of HBME-1, carcinoma antigen 19-9 (CA 19-9), and CD-15 (Leu-M1) was tested on 59 cell block preparations from fine-needle aspirations of the thyroid gland. HBME-1 monoclonal antibody was reactive in all 21 papillary carcinomas, in 4 of 18 adenomas, and in 5 of 20 goiters. CA 19-9 was identified in 13 of 21 carcinomas, 1 goiter, but none of the adenomas. CD-15 was present in 15 of 21 carcinomas, 1 goiter, and 1 adenoma. We conclude that HBME-1 is a sensitive marker of papillary thyroid carcinoma. CD-15 and CA 19-9 are less sensitive but more specific. This panel can be useful to help classify morphologically equivocal lesions. As with all immunocytochemical testing, caution must be exercised in the interpretation of results, and correlation made with morphologic and clinical data.

Adenoma↗

PubMed1998

Cell-type- and tumour-type-related patterns of bcl-2 reactivity in mesenchymal cells and soft tissue tumours.

Bcl-2 is one of the many proteins that regulate programmed cell death and is overexpressed in B-cell lymphomas. The expression of bcl-2 in mesenchymal cells and soft tissue tumours was the subject of this study. Normal mesenchymal tissue and representative cases of soft tissue tumours of different types (n>200) were investigated immunohistochemically for bcl-2 expression. Although bcl-2 expression was normally relatively restricted to some smooth muscle cells and neural cells, bcl-2 immunoreactivity was widespread in different types of soft tissue neoplasms, both benign and malignant. Consistently positive tumours included solitary fibrous tumour, haemangiopericytoma, schwannoma and synovial sarcoma. The few soft tissue tumours that were consistently negative for bcl-2 included nodular fasciitis and desmoid tumour. Leiomyomas and leiomyosarcomas were heterogeneous; all uterine leiomyomas were bcl-2 positive, but all oesophageal leiomyomas were negative, paralleling the reactivity observed in the smooth muscle at those sites. Gastrointestinal stromal tumours showed bcl-2 reactivity; this was less consistent in malignant tumours. Along the malignancy gradient, there was no consistent trend in the bcl-2 reactivity. Dermatofibrosarcomas showed increase of bcl-2 expression with fibrosarcomatous transformation, whereas smooth muscle sarcomas and malignant peripheral nerve sheath sarcomas were less consistently positive than the corresponding benign neoplasms. We conclude that bcl-2 expression is widespread in soft tissue tumours, but shows constitutional expression patterns that are often parallel to the normal tissue counterparts. Compared with benign soft tissue tumours, bcl-2 expression is often reduced in sarcomas, but it cannot be used as a prognostic marker without correlation of the data to its phenotypic expression patterns.

Biomarkers, Tumor↗

PubMed1998

DNA copy number changes in development and progression in leiomyosarcomas of soft tissues.

DNA copy number changes were investigated in 29 leiomyosarcomas by comparative genomic hybridization. The most frequent losses were detected in 10q (20 cases, 69%) and 13q (17 cases, 59%). The most frequent gains were detected in 17p (16 cases, 55%). The most frequent high-level amplifications were detected in 17p (7 cases, 24%) and 8q (6 cases, 21%). A total of 137 losses and 204 gains were detected. Small tumors (less than 5 cm in diameter) displayed fewer changes per sample (3 to 11; mean, 7) than the other tumors (4 to 22; mean, 13). There was an increase in the number of gains from small tumors (mean, 4) to very large tumors (>20 cm; mean, 10). However, the number of losses was similar in small, large, and very large tumors (mean, 4.5). Tumor size-related aberrations were observed. Gains in 16p were detected in all small tumors but were infrequent in large and very large tumors (27% and 11%, respectively). Similarly, gains and high-level amplifications in 17p were more common in small (80%) than in very large tumors (33%). Gains in 1q, 5p, 6q, and 8q were not seen in any of the small tumors but were detected in large and very large tumors. Gains in 6q and 8q occurred in 8 of 9 cases (89%) of very large tumors, 5 of them with a high-level amplification in 8q.

Adult↗

PubMed1998

Calcifying aponeurotic fibroma: a clinicopathologic study of 22 cases arising in uncommon sites.

Calcifying aponeurotic fibroma is a rare soft tissue tumor that primarily occurs in children and adolescents and has a strong predilection for the distal portion of the extremities, especially the hands and feet. This report describes 22 previously unpublished cases arising in uncommon sites. Fifteen patients were male, and seven were female (age range, 2 to 43 years; median age, 9 years). The process typically presented as a painless mass and was present from 2 weeks to 11 years before resection. Sites of involvement were the back (n=8), knee region (n=5), thigh (n=3), forearm (n=3), elbow (n=2), and arm, not otherwise specified (n=1). The lesions were often adherent to dense fibrous connective tissue (eg, tendon, fascia, or periosteum) and ranged from 1.0 to 5.0 cm in maximum dimension. The process typically had an irregular contour and a firm, fibrous consistency. Sometimes minute foci with a calcific appearance were evident grossly. Microscopic examination showed spindled fibroblasts with a fascicular growth pattern and scattered epithelioid cells bordering chondroid foci with or without mineralization. Immunoreactivity was present for vimentin (six of six), muscle-specific actin (three of six), smooth muscle actin (three of six), CD99 (five of five), CD34 (one of six), CD57 (one of six, trace), EMA (two of six, trace), S100 protein (five of six), CD68 (five of five), and progesterone receptor (one of six). The tumors were managed by local excision (n=20), incomplete local excision (n=1) and biopsy only (n=1). Follow-up information was available for 10 patients with a median follow-up interval of 94 months. Five patients (50%) developed one or more recurrences. Familiarity with this entity should help to avoid confusion with other processes, including infantile and extraabdominal fibromatoses, a chondroma of soft parts, and a fibrous hamartoma of infancy.

Adolescent↗

PubMed1998

Different patterns of DNA copy number changes in gastrointestinal stromal tumors, leiomyomas, and schwannomas.

It is not uniformly agreed whether gastrointestinal stromal tumors (GISTs) are phenotypical variants of leiomyomas (cellular leiomyomas) or whether they represent a separate, genotypically definable entity. In an attempt to solve this question, we examined immunohistochemically defined leiomyomas from the esophagus and uterus, gastric schwannomas, and benign gastrointestinal stromal tumors (GIST) by comparative genomic hybridization (CGH). All 14 leiomyomas (nine esophageal, five uterine) were actin- and desmin-positive but negative for CD34 and S100-protein. Changes in DNA copy numbers were seen only in three esophageal leiomyomas. Gains were observed in chromosomes 3, 4, 5, 8, and 17, whereas losses were seen in 16p. All schwannomas were positive for S100-protein and negative for actin, desmin, and CD34. In schwannomas, the only change by CGH was a gain in 11q in one case. The benign GISTs, all from the stomach, were positive for CD34 but negative for desmin and S100-protein; two cases were positive for actin. The CGH findings in the GISTs differed markedly from those in leiomyomas and schwannomas. Ten of the 13 cases (77%) showed DNA copy number losses in 14q, and additional or other losses were found in eight cases, most often in chromosome 22 (seven cases), 15 (three cases), and 1p (two cases). Furthermore, two of the GISTs showed gains in 5q. These results indicate that phenotypically undifferentiated GISTs are also genetically different from leiomyomas and schwannomas and support their classification apart from leiomyomas.

Actins↗

PubMed1998

Keratin subsets and monoclonal antibody HBME-1 in chordoma: immunohistochemical differential diagnosis between tumors simulating chordoma.

Thirty-five chordomas and more than 100 other tumors that have to be considered in the differential diagnosis, were immunohistochemically analyzed using a panel of antibodies including those to subsets of keratins (K), HBME-1, a monoclonal antibody recognizing an unknown antigen on mesothelial cells, and neuroendocrine markers. The patterns of immunoreactivities in chordoma were compared with those in renal cell carcinoma, colorectal mucinous adenocarcinoma, pituitary adenoma, skeletal chondrosarcoma, and extraskeletal myxoid chondrosarcoma (ESMC). Chordomas were consistently positive for keratin cocktail AE1/AE3, and for the individual keratins K8 and K19, and nearly always positive for K5, but they showed negative or only sporadic reactivity for K7 and K20. The keratin K8 and K19 reactivity was retained in those chordomas showing solid sheets of epithelioid, spindle cells, or cartilaginous metaplasia, and in one of two cases showing overtly sarcomatous transformation. In comparison, keratins were never present in skeletal chondrosarcoma, although K8 and to a lesser extent K19 were seen in occasional cases of ESMC with chordoid features. HBME-1 reacted strongly with chordoma and skeletal chondrosarcoma but was almost never positive in renal or colorectal carcinoma. These carcinomas lacked K5-reactivity, in contrast to chordoma. Chordomas were also consistently positive for neuron-specific enolase and occasionally focally for synaptophysin, but never for chromogranin. In contrast, pituitary adenomas regularly expressed the full spectrum of neuroendocrine markers and differed from chordoma by having a narrower repertoire of keratins, often showing negative or focal keratin 8- or AE1/AE3 reactivity and being almost always K19-negative. These findings indicate that chordoma can be immunohistochemically separated from tumors that can resemble it. Immunohistochemistry is especially useful in the diagnosis of small biopsy specimens that offer limited material for morphological observation.

Adenocarcinoma, Mucinous↗

PubMed1998

Molecular pathological analysis of testicular diffuse large cell lymphomas.

The molecular pathology of 20 lymphomas, which presented as testicular masses in patients with no evidence of previous lymphoma, was analyzed. These lymphomas occurred in men with a median age of 69 years (range, 37 to 87 years). Nine of the 14 patients with follow-up died of lymphoma (median survival, 12 months). All cases were diffuse large B-cell lymphomas that were positive for CD20 and commonly showed plasmacytoid differentiation (10 of 20 cases). Three cases were Burkitt's-like large cell lymphomas. Infiltration by lymphoma in the seminiferous tubules was seen in most cases. All lymphomas were negative for human herpesvirus 8 and Epstein-Barr virus by 35 cycles of polymerase chain reaction (PCR), suggesting that these viruses are not involved in the pathogenesis of primary testicular diffuse large B-cell lymphomas (DLBCL). PCR-based studies for t(14;18) and t(11;14) translocations, commonly seen in follicular and mantle-cell lymphomas, were negative in all cases. Nucleotide sequences of the V-D- and J segments of the immunoglobulin heavy chain gene (IgH) rearrangements obtained in 12 cases after PCR amplification were analyzed and compared with known germlines. The frequency of VH-family use in testicular DLBCL was similar to that reported for normal peripheral blood lymphocytes and follicular lymphomas. This contrasts with the previously published findings of preferential use of the VH3- or VH4-family by nodal DLBCL. Comparison with the published germlines showed a low similarity index in most of the cases, suggesting the presence of extensive somatic mutations. Ongoing mutation, as indicated by intraclonal variation in IgH sequence, was observed in all sequenced cases, suggesting direct antigen stimulation, which represents another difference between primary testicular and nodal DLBCL. Our results suggest that testicular lymphomas represent a subset of DLBCL that differs from their nodal counterparts in several respects. Their histological and molecular features show some similarities to those seen in marginal zone (MALT) lymphomas.

Adult↗

PubMed1998

Collagenous fibroma (desmoplastic fibroblastoma): a clinicopathologic analysis of 63 cases of a distinctive soft tissue lesion with stellate-shaped fibroblasts.

Sixty-three cases of collagenous fibroma (desmoplastic fibroblastoma) from the files of the Armed Forces Institute of Pathology were analyzed. These tumors occurred mostly in men (80%) with a median age of 50 years (range, 16 to 81 years). The lesions had a wide anatomic distribution and involved the arm (24%), shoulder girdle (19%), posterior neck or upper back (14%), feet or ankles (14%), leg (14%), hand (8%), and abdominal wall and hip (6%). The patients typically presented with a history of a painless, slowly growing mass, often of relatively long duration. The tumors ranged in size from 1 to 20 cm (median, 3.0 cm). The lesions were predominantly subcutaneous, but fascial involvement was common, and 27% of cases involved skeletal muscle. Gross examination typically showed an elongated, lobulated, or disc-shaped mass with a firm consistency and a homogeneous pearl-gray color. Histologically, the tumors often appeared well marginated on low-power examination, but most (78%) infiltrated fat or, less commonly, skeletal muscle. The lesional cells were relatively bland stellate and spindle-shaped fibroblasts separated by a collagenous or myxocollagenous matrix. Mitotic activity was absent or minimal. Some of the lesional cells had a myofibroblastic immunophenotype, as evidenced by focal reactivity for muscle-specific and alpha-smooth muscle actins. In a few cases, rare actin-positive cells were also positive for keratins. Desmin, S100 protein, and CD34 were not expressed. None of the 39 patients with follow-up (median, 11 years) developed a recurrence. Collagenous fibroma is a benign fibroblastic/myofibroblastic proliferation. The large size of some of these tumors coupled with slow growth and persistence favors a neoplastic process over a peculiar reactive proliferation. The differential diagnosis includes a variety of reactive and neoplastic fibroblastic lesions, most importantly fibromatosis and low-grade fibromyxoid sarcoma. Simple, conservative excision is the treatment of choice for collagenous fibroma.

Adolescent↗

PubMed1998

Extrarenal rhabdoid tumors of soft tissue: a clinicopathologic and immunohistochemical study of 18 cases.

Rhabdoid tumor is a well-accepted clincopathologic entity among childhood renal neoplasms; similar tumors have been described in extrarenal locations. We present the clinicopathologic profile and the immunohistochemical features of a series of soft tissue rhabdoid tumors. Twenty-eight cases coded as extrarenal rhabdoid tumor (ERRT), RT, possible ERRT, and "large cell sarcoma" were retrieved from the Armed Forces Institute of Pathology soft tissue registry. The tumors were reclassified according to strict criteria by light microscopy, clinical information, immunohistochemistry, and, in some cases, electron microscopy. Soft tissue rhabdoid tumor (STRT) was defined as (1) a tumor composed of noncohesive single cells, clusters, or sheets of large tumor cells with abundant glassy eosinophilic cytoplasm, an eccentric vesicular nucleus, and an extremely large nucleolus; (2) positivity for vimentin and/or cytokeratin or other epithelial markers by immunostaining; and (3) exclusion of other tumor types with rhabdoid inclusions (melanoma, other sarcomas, carcinoma). Eighteen cases met our criteria for soft tissue rhabdoid tumors. The median patient age was 13 years (range, 6 months to 56 years). Ninety-four percent of STRT cases were positive for vimentin and 59% for pan-cytokeratin. Sixty-three percent and 60% were positive for CAM 5.2 and EMA, respectively. Seventy-nine percent stained for at least one epithelial marker; 76% stained for both vimentin and epithelial markers simultaneously. Forty-two percent stained for MSA, and 14% for CEA and SMA. CD99, synaptophysin, CD57 (Leu-7), NSE, and focal S100 protein were identified in 75%, 66%, 56%, 54%, and 31% of the STRT cases, respectively. All STRT cases examined were negative for HMB-45, chromogranin, BER-EP4, desmin, myoglobin, CD34, and GFAP. Follow-up examination in 61% of the STRT patients revealed that 64% of patients died of disease within a median follow-up interval of 19 months (range, 4 months to 5 years); 82% had metastases to lung, lymph nodes, or liver; 22% had local recurrences before metastasis; and 18% were alive without known disease status (median, 5.5 years). Soft tissue rhabdoid tumor is a highly aggressive sarcoma, predominantly of childhood. Besides having nearly consistent coexpression of vimentin and epithelial markers, STRTs show positivity for multiple neural/neuroectodermal markers that overlap with those of primitive neuroectodermal tumor.

Adolescent↗