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M Miettinen

Publications and source records attributed to M Miettinen.

At least 19 recordsLinked to original sources
PubMed2006

Measurement of oedema in irritant-exposed skin by a dielectric technique.

BACKGROUND: Easily applicable water-specific instruments measuring local oedema in skin are not available. The aim of this study is to demonstrate quantitative assessment of skin oedema with the dielectric technique by measuring increase of skin water content related to sodium lauryl sulphate (SLS)-induced irritant contact dermatitis. METHODS: Irritant skin reaction and resulting oedema were induced by an irritant patch test on volar forearms in 12 healthy volunteers with the application of 1% SLS for 6 h. After occlusion the volunteers were divided into two groups: the patch test site of group I (six volunteers) received no treatment other than a base cream for the skin reaction, while for group II (six volunteers) a strong corticosteroid (clobetasol propionate) was applied on the irritant skin. During a follow-up of 72 h, erythema was scored visually, and irritant-induced oedema was measured with a novel water-specific instrument MoistureMeter-D. RESULTS: In the untreated irritant skin, a maximum increase of 45% in skin water content was found at 10 h postocclusion and water content was still elevated at 72 h. With these persons, the degree of oedema agreed well with the ultrasound-measured skin thickness (P=0.053). In the corticosteroid-treated skin, an increase of 8% in water content was measured during 72 h but there was no correlation between oedema and skin thickness. There was no correlation between erythema and oedema in untreated or corticosteroid-treated skin. CONCLUSION: The new instrument can easily be applied for noninvasive quantitative evaluation of local oedema and fluid retention in irritant-exposed skin.

Adult↗
PubMed2006

Evaluation of biological potential of smooth muscle tumours.

Smooth muscle tumours (SMTs) have been traditionally divided into benign leiomyomas (LM) and malignant leiomyosarcomas (LMS) based on cytological atypia, mitotic activity and other criteria. In most instances, this dichotomous approach works, but in some instances the biological potential cannot be determined with certainty. This is often because some, but not all criteria for malignancy have been met or because the tumours are occurring in unusual settings for which there are sparse substantive data. Tumours falling into the latter categories are often designated as 'smooth muscle tumours of uncertain malignant potential'. For most non-hormonally influenced SMTs, the presence of significant atypia plus mitotic activity equates with a diagnosis of LMS. However, not all tumours classified as LMSs have a similar prognosis, as a number of other factors, including tumour size, depth, grade and resectability, affect outcome. For example, cutaneous SMTs, regardless of mitotic activity and atypia, have potential largely limited to local recurrence, whereas subcutaneous and deep LMSs have a definite metastatic potential. Angioleiomyoma is the most common SMT of peripheral soft tissues, but deep peripheral LMs are distinctly rare and should be approached with caution. Hormonally influenced oestrogen- and progesterone receptor-positive uterine and extrauterine SMTs in women have unique criteria, including the allowance of higher mitotic activity for the benign LM designation. SMTs of female genital tract can be assessed with criteria similar to uterine tumours. Because of the rarity of these tumours, experience is more limited, and more caution is needed to assess the potential of tumours with mitotic activity and atypia. This review summarizes the current knowledge, guidelines, prognostic data and controversies for the classification of SMTs of soft tissue and most visceral sites.

Actins↗
PubMed2005

KIT-positive gastrointestinal stromal tumor in a 22-year-old male chimpanzee (Pan troglodites).

Gastrointestinal stromal tumors (GIST), KIT-positive and KIT signaling driven or platelet-derived growth factor receptor alpha (PDGFRA) signaling driven mesenchymal tumors, are poorly known in nonhuman primates. Availability of KIT- and PDGFRA-inhibitor drug imatinib mesylate has greatly raised the interest for these tumors. At necropsy of a 22-year-old male chimpanzee, a round, firm 2-cm intramural tumor was incidentally found in the midbody of the stomach and diagnosed as a GIST. Histologically, the mass was composed of spindle to polygonal epithelioid cells arranged in short to intermediate-length, interlacing streams, bundles, and nodular whorls often separated by hyalinized eosinophilic matrix. The mitotic rate was a maximum 1/50 high-power field. Immunohistochemically, the tumor cells were diffusely positive for KIT and CD34, focally positive for alpha-smooth muscle actin, and negative for muscle specific actin, desmin, S-100 protein, synaptophysin, and glial fibrillary acidic protein. Because the majority of human GISTs have gain-of-function KIT or PDGFRA mutations, genomic sequences of KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 from this chimpanzee GIST were polymerase chain reaction amplified and sequenced. However, no mutation was identified in the analyzed "mutational hot spots." This study is the first extensive histomorphologic, immunohistochemical, and molecular genetic analysis of a chimpanzee GIST. More cases of nonhuman primate GISTs should be analyzed to discover the clinicopathologic spectrum of GISTs in these species.

Animals↗
PubMed2004

Lingual alveolar soft part sarcoma; 14 cases: novel clinical and morphological observations.

AIMS: Alveolar soft part sarcoma (ASPS) is a rare sarcoma in the buttocks or thigh of young adults, often with metastases to lung, brain, or bone. This study examines the morphological and clinical features of lingual ASPS. METHODS AND RESULTS: Fourteen cases, in eight males and six females (ages 3-21 years, median 5 years), ranged from 8 to 50 mm, median 25 mm. All tumours were intramuscular, circumscribed and multinodular. Tumours from all but the oldest patient exhibited a predominantly solid (non-alveolar) growth pattern. Vascular invasion was common. Crystals varied in number from none or extremely rare to nearly 100% of tumour cells. Immunohistochemical results: Fifty percent desmin positive, all focally smooth muscle antigen (SMA) positive; negative for vimentin, neural/melanocytic, myoid, histiocytic, and epithelial markers. All tumours were surgically excised; only two patients received chemotherapy. Follow-up on 10 patients showed that all patients were alive without disease (4-32, median 22 years). Only one patient had a microscopic metastasis to lung (3 years) but was without disease at 11 years. CONCLUSIONS: Lingual ASPS is a tumour of childhood with a distinctive, predominantly solid growth pattern. Despite typical vascular invasion, the early diagnosis and small tumour size may explain its relatively good outcome.

Adolescent↗
PubMed2004

Molecular targets for tumour progression in gastrointestinal stromal tumours.

BACKGROUND AND AIMS: The distinction between benign and malignant gastrointestinal stromal tumours (GISTs) is often unclear at the clinical and histopathology levels. GISTs are believed to arise from the stem cells of Cajal. In order to define genetic biomarkers and identify target genes related to GIST progression, we analysed and compared benign and malignant GISTs with verified follow up data using cDNA expression arrays. METHODS: Eight genes were frequently overexpressed in malignant GISTs and their overexpression was confirmed using quantitative real time reverse transcription-polymerase chain reaction. These genes included ezrin (villin 2 (VIL2)), collagen 8 alpha 1 subunit (COL8A1), G2/mitotic specific cyclin B1 (CCNB1), high mobility group protein (HMG2), TSG101 tumour susceptibility protein, CENP-F kinetochore protein, protein tyrosine kinase 2 (FAK), and protein kinase DYRK2. To test these genes in a clinical setting, we obtained diagnostic samples of 16 additional GISTs that were classified at diagnosis as benign, malignant, and uncertain malignant potential (UMP). RESULTS: There was remarkable gene overexpression in all malignant GISTs. Statistical analyses revealed significant correlations between overexpression of several gene pairs in malignant GISTs. We found the strongest correlations (rho>0.70) among the significant correlations (p<0.01) between CCNB1-CENP-F (rho = 0.87) and CCNB1-FAK (rho = 0.73). Gene expression of the UMP GISTs suggested two different groups. Three UMP GISTs had gene expression consistent with malignant tumours and their follow up data revealed that indeed these patients had recurrences later on. On the other hand, UMP GISTs that had low gene expression levels continued free of disease for several years. CONCLUSIONS: These results provide insight into the oncogenesis of GISTs and suggest that testing the expression profile of a number of genes may segregate GISTs into groups of different tumour behaviour.

Chromosomal Proteins, Non-Histone↗
PubMed2003

Gastrointestinal stromal tumors and leiomyomas in the dog: a histopathologic, immunohistochemical, and molecular genetic study of 50 cases.

Fifty canine gastrointestinal (GI) mesenchymal tumors were examined to determine the occurrence of leiomyomas (LM) and GI stromal tumors and to compare their clinicopathologic features. Twenty-one tumors (42%) were histologically reclassified as gastrointestinal stromal tumors (GISTs) and 29 tumors (58%) as LMs on the basis of their histologic similarity with homologous human tumors. The GISTs occurred equally in males and females, with a mean age of 11 years (range 5-14 years). Five GISTs (24%) were associated with clinical signs and six (29%) had metastasis in liver or abdominal cavity. The GISTs occurred in large intestine (10, 48%), small bowel (six, 29%), stomach (four, 19%), and mesentery of small intestine (one, 5%). Histologically, they were highly cellular spindle, or less commonly epithelioid tumors with mitotic rates ranging from 0 to 19 per 10 HPF. Eleven tumors (52%) were positive for CD117 (KIT); seven (33%) were positive for smooth muscle actin but none for desmin and S-100 protein. Sequences of KIT exon 11, often mutated in human GISTs, were evaluated from four GISTs. Deletion of Try556-Lys557 coexisting with duplication of Gln555 in one case of GIST and T to C transition resulting in substitution of Pro for Leu575 in another were identified. The LMs occurred predominantly in males (82%) with a mean age of 11 years (range 8-17 years). Nine tumors (31%) had associated clinical signs. They occurred in the stomach (22, 76%), esophagus (four, 14%), and intestines (three, 10%); all were paucicellular, had no mitoses, and were composed of mature smooth muscle cells. Twenty-eight (97%) were positive for smooth muscle actin and 18 (62%) for desmin but none for CD117 and S-100. Both GISTs and true LMs occur in the GI tract of dogs. Both tumors have distinctive pathologic features.

Amino Acid Sequence↗
PubMed2001

Chromosomal aberrations in malignant gastrointestinal stromal tumors: correlation with c-KIT gene mutation.

Gastrointestinal stromal tumors (GISTs) are distinctive, KIT positive mesenchymal neoplasms. The genetic alterations leading to the malignant behavior of these tumors are not well known. In this study, we looked for recurrent numerical chromosomal changes, which may be associated with malignant GISTs, using interphase fluorescence in situ hybridization (FISH). Fourteen malignant primary tumors and two intra-abdominal recurrences were analyzed. Nine benign tumors were studied for comparison. In all cases, the presence of mutations in exons 9, 11 and 13 of the KIT gene were evaluated. Sixteen centromeric enumeration probes (CEP) for chromosomes 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 15, 16, 17, 18, and X and three locus specific probes (LSI) for 22q11.2 (BCR-locus), 13q14 (RB1-locus) and 14q32 (IgH-locus) were used. The most common changes seen in malignant GISTs were losses of 14q32 and 22q11. However, these changes were commonly detected in benign tumors and represent early changes related to the pathogenesis of GISTs. Losses of chromosomes 1 and 9 were the only recurrent numerical changes seen exclusively in malignant GISTs. Other recurrent numerical changes seen predominantly in malignant tumors were gain of chromosome 8 and losses of chromosomes 7 and 15. The concurrent loss of chromosome 7 and gain of chromosome 8 (in 4 cases) was never seen together with loss of chromosomes 9 or 15 and only once with loss of chromosome 1. Mutations in KIT were found in the majority of malignant GISTs (64%) confirming a previously shown correlation between presence of such mutations and malignancy. KIT mutations were seen in four of five malignant GISTs with loss of chromosome 9, but only in one of four malignant tumors with loss of chromosome 1. These observations may reflect the different pathways leading to malignant transformation of GISTs.

Adult↗
PubMed2001

Infection of human macrophages and dendritic cells with Mycobacterium tuberculosis induces a differential cytokine gene expression that modulates T cell response.

Macrophages and dendritic cells (DC) play an essential role in the initiation and maintenance of immune response to pathogens. To analyze early interactions between Mycobacterium tuberculosis (Mtb) and immune cells, human peripheral blood monocyte-derived macrophages (MDM) and monocyte-derived dendritic cells (MDDC) were infected with Mtb. Both cells were found to internalize the mycobacteria, resulting in the activation of MDM and maturation of MDDC as reflected by enhanced expression of several surface Ags. After Mtb infection, the proinflammatory cytokines TNF-alpha, IL-1, and IL-6 were secreted mainly by MDM. As regards the production of IFN-gamma-inducing cytokines, IL-12 and IFN-alpha, was seen almost exclusively from infected MDDC, while IL-18 was secreted preferentially by macrophages. Moreover, Mtb-infected MDM also produce the immunosuppressive cytokine IL-10. Because IL-10 is a potent inhibitor of IL-12 synthesis from activated human mononuclear cells, we assessed the inhibitory potential of this cytokine using soluble IL-10R. Neutralization of IL-10 restored IL-12 secretion from Mtb-infected MDM. In line with these findings, supernatants from Mtb-infected MDDC induced IFN-gamma production by T cells and enhanced IL-18R expression, whereas supernatants from MDM failed to do that. Neutralization of IFN-alpha, IL-12, and IL-18 activity in Mtb-infected MDDC supernatants by specific Abs suggested that IL-12 and, to a lesser extent, IFN-alpha and IL-18 play a significant role in enhancing IFN-gamma synthesis by T cells. During Mtb infection, macrophages and DC may have different roles: macrophages secrete proinflammatory cytokines and induce granulomatous inflammatory response, whereas DC are primarily involved in inducing antimycobacterial T cell immune response.

Biomarkers↗
PubMed2001

Vitamin C enhances differentiation of a continuous keratinocyte cell line (REK) into epidermis with normal stratum corneum ultrastructure and functional permeability barrier.

A continuous rat epidermal cell line (rat epidermal keratinocyte; REK) formed a morphologically well-organized epidermis in the absence of feeder cells when grown for 3 weeks on a collagen gel in culture inserts at an air-liquid interface, and developed a permeability barrier resembling that of human skin. By 2 weeks, an orthokeratinized epidermis evolved with the suprabasal layers exhibiting the differentiation markers keratin 10, involucrin, and filaggrin. Granular cells with keratohyalin granules and lamellar bodies, and corneocytes with cornified envelopes and tightly packed keratin filaments were present. Morphologically, vitamin C supplementation of the culture further enhanced the normal wavy pattern of the stratum corneum, the number of keratohyalin granules present, and the quantity and organization of intercellular lipid lamellae in the interstices of the stratum corneum. The morphological enhancements observed with vitamin C correlated with improved epidermal barrier function, as indicated by reduction of the permeation rates of tritiated corticosterone and mannitol, and transepidermal water loss, with values close to those of human skin. Moreover, filaggrin mRNA was increased by vitamin C, and western blots confirmed higher levels of profilaggrin and filaggrin, suggesting that vitamin C also influences keratinocyte differentiation in aspects other than the synthesis and organization of barrier lipids. The unique REK cell line in organotypic culture thus provides an easily maintained and reproducible model for studies on epidermal differentiation and transepidermal permeation.

Animals↗
PubMed2001

Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. They are defined here as KIT (CD117, stem cell factor receptor)-positive mesenchymal spindle cell or epithelioid neoplasms primary in the GI tract, omentum, and mesentery. GISTs typically present in older individuals and are most common in the stomach (60-70%), followed by small intestine (20-25%), colon and rectum (5%), and esophagus (<5%). Benign tumors outnumber the malignant ones by a wide margin. Approximately 70% of GISTs are positive for CD34, 20-30% are positive for smooth muscle actin (SMA), 10% are positive for S100 protein and <5% are positive for desmin. The expression of CD34 and SMA is often reciprocal. GISTs commonly have activating mutations in exon 11 (or rarely exon 9 and exon 13) of the KIT gene that encodes a tyrosine kinase receptor for the growth factor named stem cell factor or mast cell growth factor. Ligand-independent activation of KIT appears to be a strong candidate for molecular pathogenesis of GISTs, and it may be a target for future treatment for such tumors. Other genetic changes in GISTs discovered using comparative genomic hybridization include losses in 14q and 22q in both benign and malignant GISTs and occurrence in various gains predominantly in malignant GISTs. GISTs have phenotypic similarities with the interstitial cells of Cajal and, therefore, a histogenetic origin from these cells has been suggested. An alternative possibility, origin of pluripotential stem cells, is also possible; this is supported by the same origin of Cajal cells and smooth muscle and by the common SMA expression in GISTs. GISTs differ clinically and pathogenetically from true leiomyosarcomas (very rare in the GI tract) and leiomyomas. The latter occur in the GI tract, predominantly in the esophagus (intramural tumors) and the colon and rectum (muscularis mucosae tumors). They also differ from schwannomas that are benign S100-positive spindle cell tumors usually presenting in the stomach. GI autonomic nerve tumors (GANTs) are probably a subset of GIST. Other mesenchymal tumors that have to be separated from GISTs include inflammatory myofibroblastic tumors in children, desmoid, and dedifferentiated liposarcoma. Angiosarcomas and metastatic melanomas, both of which are often KIT-positive, should not be confused with GISTs.

Amino Acid Sequence↗
PubMed2001

The neurofibromatosis type 2 gene is mutated in perineurial cell tumors: a molecular genetic study of eight cases.

Perineurial cell tumors (PNTs) are rare neoplasms derived from or showing differentiation toward specialized lining cells of the nerve sheath, the perineurial cells. In this study, we have evaluated neurofibromatosis type 2 (NF2) gene alterations in eight PNTs using archival formaldehyde-fixed, paraffin-embedded tissue. Two conventional soft-tissue PNTs from the upper back and chest wall, one retiform soft tissue variant from the scapular region, and five sclerosing PNTs from the fingers and palm were studied. All cases showed histological features of PNTs, and the neoplastic cells were positive for epithelial membrane antigen and negative for S100 protein. The coding sequences (exons 1 to 15) of the NF2 gene were polymerase chain reaction (PCR) amplified and evaluated for mutations by direct sequencing of the PCR products. Five NF2 point mutations, two in the 5'-untranslated region (UTR) and three in exons 3, 6, and 8, were identified in four of eight cases (50%) studied. Exon mutations resulted in changes of predicted amino acids sequences: Asp-->Asn at codon 83, Glu-->Asp at codon 182, and Leu-->Val at codon 241. In two cases (one with a missense mutation in codon 241), the same point mutation in the 5'-UTR at the nucleotide position 8958 was identified. A loss of heterozygosity (LOH) study was performed in three cases. LOH at the NF2 locus was found in one case with a mutation in the 5'-UTR. However, in another case with exon 8 and 5'-UTR mutations, deletion of one allele of the NF2 gene was previously documented by fluorescence in situ hybridization. The coexistence of NF2 gene mutations and LOH at the NF2 locus indicates that the NF2 tumor suppressor gene is altered in PNTs by the two-hit mechanism.

Adolescent↗
PubMed2001

Mesenchymal tumors of muscularis mucosae of colon and rectum are benign leiomyomas that should be separated from gastrointestinal stromal tumors--a clinicopathologic and immunohistochemical study of eighty-eight cases.

Most mesenchymal tumors of the gastrointestinal tract are currently classified as specific gastrointestinal stromal tumors. However, true leiomyomas are more common in the esophagus, and they have been occasionally noted in the colon and rectum, but the small number of reported cases does not allow for clinicopathologic profiling. This study was undertaken to characterize 88 tumors of the muscularis mucosae of the colon and rectum. Seventy tumors were obtained form the files of AFIP and 18 cases from the Department of Pathology of the Haartman Institute of the University of Helsinki. The lesions, except one, were removed by snare polypectomy as incidental lesions at cancer or polyp surveillance; one small tumor was an incidental finding in the rectal resection specimen. The tumors had a significant male predominance in both institutions (overall 2.4:1). They occurred in age range of 38 to 85 years (median 62 years). The lesions were typically small (range 1 to 22 mM, median 4 mM) and located predominantly in the rectum and sigmoid (72%). All tumors were composed of well-differentiated, eosinophilic smooth muscle cells that were seen immediately beneath the mucosa obliterating the muscularis mucosae layer and merging with it. Two tumors had significant atypia ("symplastic leiomyoma"); mitotic activity was seen in one of these tumors, but not in others. The lesional cells were uniformly positive for smooth muscle actin and desmin and negative for CD34, CD117 and S100-protein, based on immunohistochemical studies on 20 to 24 cases with each marker. No gastrointestinal stromal tumors were identified among the tumors of muscularis mucosae, and no CD117-positive cells, except mast cells, were seen in the muscularis mucosae layer. None of the patients had morbidity related to the tumor. Based on follow-up data on 29 patients, leiomyomas of muscularis mucosae are benign. They should be separated from gastrointestinal stromal tumors that have a clinicopathologic spectrum including frequent disease-related mortality. Snare polypectomy is an adequate treatment, but ensuring the complete removal and follow-up are necessary precautions for tumors with any atypia or mitotic activity.

Actins↗
PubMed2001

Differentiating lymphoblastic lymphoma and Ewing's sarcoma: lymphocyte markers and gene rearrangement.

We encountered a child with an intraosseous small round cell tumor that was negative for LCA, CD20 (L26), and CD3 and positive for vimentin, CD99 (MIC-2), and periodic acid-Schiff. The tumor exhibited rosette-like formations. This case was initially interpreted as Ewing's sarcoma (ES); however, additional studies revealed positivity for CD79a, CD43, and TdT expression, and an immunoglobulin heavy chain gene rearrangement (IgH-R) by polymerase chain reaction (PCR) established this to be a precursor B-lymphoblastic lymphoma. Because the differential diagnosis of ES and lymphoblastic lymphoma can be difficult and the differential diagnostic value of leukocyte antigens and immunoglobulin heavy chain gene rearrangement studies have not been fully evaluated, we conducted a more extensive investigation on 33 (21 soft tissue and 12 intraosseous) ES cases. Cases were retrieved from the files of the Department of Pathology at Georgetown University and from the Soft Tissue Registry of the Armed Forces Institute of Pathology. The cases were studied by light microscopy, immunohistochemistry, and PCR for IgH-R and T cell receptor gamma chain gene rearrangement (Tgamma-R). There were 17 females and 16 males; the mean age was 29.3 years. Locations included the extremities (n = 17) and trunk (n = 16). All cases fit the ES spectrum by light microscopy and immunohistochemistry, as previously determined, and were negative for lymphoid markers (LCA, CD3, CD20, CD43, CD79a, and TdT), CD10 and CD34. CD99 was positive in 31/33 and bcl-2 was weakly positive in 13/33 cases. All 21 cases studied for gene rearrangements by PCR were negative for IgH-R and Tgamma-R. Distinction of intraosseous lymphoblastic lymphoma from ES may be difficult because lymphomas may occasionally exhibit unexpected morphologic and immunophenotypic properties including LCA, CD3 and CD20 negativity and cytokeratin positivity. Additional analysis using CD79a, CD43, TdT, and PCR should be performed to avoid misdiagnosis. True ES is negative for lymphoid markers including CD79a, CD43, and TdT, as well as for IgH-R and Tgamma-R.

12E7 Antigen↗
PubMed2001

IFNs activate toll-like receptor gene expression in viral infections.

Toll-like receptors (TLRs) mediate innate immune responses to microbes. TLR2, TLR5, TLR6, and TLR9 have been implicated in responses to bacterial components, and TLR4 is the receptor for Gram-negative bacteria. Recently, TLR4 was described to function in respiratory syncytial virus-induced NF-kappaB activation. Here we have analyzed TLR1-9 mRNA expression in human primary macrophages infected with influenza A and Sendai viruses. TLR1, TLR2, TLR4, TLR6, and TLR8 mRNAs were expressed at basal levels in macrophages. Viral infection enhanced TLR1, TLR2, TLR3, and TLR7 mRNA expression, and neutralizing anti-IFN-alpha/beta antibodies downregulated gene expression of these TLRs. Exogenously added IFN-alpha upregulated TLR1, TLR2, TLR3, and TLR7 mRNA expression in macrophages, as well as TLR3 mRNA expression in epithelial and endothelial cell lines. IFN-gamma enhanced the expression of TLR1 and TLR2 mRNA in macrophages, and TLR3 in epithelial and endothelial cells. The data suggests a novel role for IFNs in the activation of innate immunity.

Antibodies↗
PubMed2001

Superficial acral fibromyxoma: a clinicopathologic and immunohistochemical analysis of 37 cases of a distinctive soft tissue tumor with a predilection for the fingers and toes.

This report describes the clinicopathologic features and immunohistochemical findings identified in 37 cases of a distinctive soft tissue tumor that has a predilection for the hands and feet. The study group included 25 male and 12 female subjects ranging in age from 14 to 72 (mean, 43; median, 46) years. The patients presented with solitary masses 0.6 to 5.0 cm (mean, 1.75 cm) that were present from 3 months to 30 years (median duration, approximately 3 years) before surgical intervention and involved the toes (n = 20), fingers (n = 13), and palm (n = 4). Twenty of the cases were documented to involve the nail region. Histologically, the tumors were typically located in the dermis or subcutis and composed of spindled and stellate-shaped cells with random, loose storiform, and fascicular growth patterns. The lesional cells were embedded in myxoid or collagenous matrix, often with mildly to moderately accentuated vasculature and increased numbers of mast cells. There was generally slight to mild nuclear atypia; only 3 cases had more substantial atypia. Mitotic figures were infrequent. Occasional multinucleated stromal cells were noted in 19 cases. The process showed immunoreactivity for CD34 (21 of 23 cases), epithelial membrane antigen (18 of 25 cases), and CD99 (11 of 13 cases). No immunoreactivity was detected for actins, desmin, keratins, or HMB-45, and only 1 of 23 tumors had weak reactivity for S100 protein. The surgical specimens consisted of biopsy or partial resection specimens (n = 4), local excisions (n = 29), and amputated or partially amputated digits (n = 4). Detailed follow-up, available for 18 patients (mean follow-up interval, 10.1 years), revealed 1 recurrence after local excision and 2 instances of persistent or progressive disease after partial excision. A differential diagnosis of fibrous histiocytoma, dermatofibrosarcoma protuberans, acquired (digital) fibrokeratoma, sclerosing perineurioma, cutaneous myxoma (superficial angiomyxoma), and acral myxoinflammatory fibroblastic sarcoma is discussed.

Adolescent↗
PubMed2001

Keratin 1 expression in endothelia and mesenchymal tumors: an immunohistochemical analysis of normal and neoplastic tissues.

Keratin polypeptides of the nonhair type, numbered 1 through 20 in the Moll catalog, are selectively expressed in normal and neoplastic tissues. Keratin 1 (K1), the highest-molecular-weight keratin (67 kd), was generally considered specific for keratinizing squamous epithelia. However, recent studies have shown that it is an integral component of the multiprotein kininogen receptor of endothelial cells. A library of formalin-fixed, paraffin-embedded tissue samples was evaluated immunohistochemically (avidin-biotin peroxidase complex method) for K1 expression using a specific monoclonal antibody (Novocastra clone 34betaB4). The study group included a wide variety of normal tissues and 541 tumors of epithelial or mesenchymal derivation. The specificity of the antibody to K1 was verified in normal epithelial tissues, where the staining was essentially limited to the epidermis and Hassal corpuscles of the thymus and focally to other squamous epithelia. Among carcinomas, it was essentially limited to keratinizing squamous carcinomas. It was also regularly found in endothelial cells of normal capillaries, veins, and arteries. Capillary, cavernous, and venous hemangiomas often had endothelia with K1 positivity. Among the malignant vascular tumors, epithelioid hemangioendotheliomas were consistently positive (8 of 8). However, angiosarcomas had more variable expression (59 of 81 were positive), with well-differentiated tumors generally having greater reactivity than poorly differentiated examples. Mesenchymal tumors with K1 expression included schwannomas (10 of 16), epithelioid sarcomas (26 of 37), and synovial sarcomas (19 of 68). In the last 2 tumor types, K1 reactivity was detected in both epithelioid and spindled neoplastic populations. In addition to its specificity for keratinizing squamous epithelia, K1 can be immunohistochemically detected in normal vascular endothelial cells and a spectrum of vascular tumors. However, its expression in poorly differentiated vascular tumors is variable, suggesting that this marker is poorly conserved in highly transformed endothelia. The unexpected K1 immunoreactivity in nonvascular soft tissue tumors, such as synovial sarcoma, epithelioid sarcoma, and schwannomas, requires further study.

Adult↗
PubMed2001

Low-affinity nerve growth factor receptor (p75) in dermatofibrosarcoma protuberans and other nonneural tumors: a study of 1,150 tumors and fetal and adult normal tissues.

Low-affinity nerve growth factor receptor (p75) is a member of the tumor necrosis factor receptor family. It may modulate the binding of nerve growth factor (NGF) to the functional high-affinity receptor tyrosine kinase (trk) A. NGF is thought to be responsible for growth, apoptosis, and function of the nervous system. The presence of this receptor (p75) was determined in a large group of neural and nonneural tumors and fetal and adult tissues. One thousand one hundred fifty tumors were analyzed with monoclonal antibody for p75, along with selected normal fetal and adult tissues. Immunoreactivity for p75 was present in adult pericytes, perivascular fibroblasts, basal cells of several types of epithelia, perineurial cells, and dendritic reticulum cells. Additionally, a wide zone of subepithelial mesenchyme and skeletal muscle were positive in the first-trimester fetus, but were diminished or negative in the adult. Consistently positive nonneural mesenchymal tumors included dermatofibrosarcoma protuberans (DFSP), embryonal and alveolar rhabdomyosarcoma, synovial sarcoma, and spindle cell hemangio(endotheli)oma. Schwann cell tumors, ganglioneuroma, granular cell tumor, and malignant peripheral nerve sheath tumor (MPNST) were also p75 positive. Mesenchymal nonneural tumors that were variably positive (32% to 69%) for p75 included fibrosarcoma variants, solitary fibrous tumor, hemangiopericytoma, spindle cell lipoma, Ewing's sarcoma, mesenchymal chondrosarcoma, and malignant melanoma. Nervous system tumors such as paragangliomas, neuroblastoma, meningioma, and perineurioma and nonneural mesenchymal tumors, including extraskeletal osteosarcoma, benign fibrous histiocytomas, fibromas, alveolar soft part sarcoma, epithelioid sarcoma, smooth muscle and gastrointestinal stromal tumors, and angiosarcomas, were almost always negative for p75. Epithelial tumors that were consistently positive included mixed tumor and adenoid cystic carcinoma, whereas mesothelioma, adenocarcinomas, and most squamous cell carcinomas were negative. p75 is not a specific marker for nerve sheath tumors. It is present in a variety of other mesenchymal tumors including synovial sarcoma and in CD34-positive tumors such as DFSP, spindle cell lipoma, and hemangiopericytoma. The presence of p75 in nonneural tumors such as DFSP and rhabdomyosarcoma mimic its presence in early fetal mesenchyme and skeletal muscle, suggesting oncofetal expression in these tumors. p75 may be useful to distinguish DFSP from benign fibrous histiocytoma.

Connective Tissue↗