Spindle-cell (Sarcomatoid) Variant of Cutaneous Anaplastic Large-cell Lymphoma (C-ALCL): An Unusual Mimicker of Cutaneous Malignant Mesenchymal Tumors-A Series of 11 Cases.

Cutaneous anaplastic large-cell lymphoma (C-ALCL) represents one of the entities within the group of CD30-positive lymphoproliferative disorders of the skin. Most cases are ALK-negative, though isolated cases of ALK-positive C-ALCL have also been reported. By definition, the diagnosis of C-ALCL requires the expression of CD30 in >75% of the cells. Histopathologically, C-ALCL shows a dermal-based nodular and circumscribed proliferation of large pleomorphic cells with vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm, including hallmark cells. Since 1990, isolated case reports of a so-called "sarcomatoid" variant have been published in the literature. Herein, we present a series of 11 cases of spindle (sarcomatoid) C-ALCL, with comprehensive histopathologic, immunophenotypic, and molecular data. Spindle C-ALCL represents a potential mimicker of malignant mesenchymal or hematopoietic tumors in the skin and should always be considered in the differential diagnosis when assessing cutaneous pleomorphic spindle cell neoplasms.

Immune cell infiltration in Ectomesenchymal chondromyxoid tumor: An immunohistochemical study.

Ectomesenchymal chondromyxoid tumor (ECT) is a rare benign neoplasm, often affecting the anterior dorsum of the tongue. To date, approximately 74 cases of lingual ECT have been published. This report describes, for the first time, the morphological and immunohistochemical features of a unique ECT case, which revealed diffuse infiltration by immune cells with a dendritic-like appearance inside the tumor proliferation. The significance of these findings and discussion about the tumor cell-immune cell interactions are presented.

A case of a CD56-expressing ectomesenchymal chondromyxoid tumor of the tongue: potential diagnostic usefulness of commonly available CD56 over CD57.

Ectomesenchymal chondromyxoid tumors (ECTs) are rare. Only approximately 55 cases have been reported in the English literature. Distinguishing ECTs from soft tissue myoepithelioma (STM) is often difficult owing to morphological and immunohistochemical similarities. Here, we present a case of an ECT arising from the anterior dorsum of the tongue in a 24-year-old woman. Grossly, the tumor was soft, had a myxoid appearance, and measured 8×7×7 mm. Microscopically, it was well-demarcated, lacked a fibrous capsule, and predominantly consisted of short, spindle to ovoid cells in a myxoid background. Vimentin, glial fibrillary acidic protein (GFAP), and S-100 protein were strongly positive on immunohistochemical analysis. While CD56 was moderately immunopositive, cytokeratin (AE1/AE3) and alpha-smooth muscle actin (αSMA) showed focal weak positivity. Thus, the immunohistochemical findings suggested a diverse immunophenotype, indicating mesenchymal (vimentin and αSMA positive), neurogenic (S100, GFAP, and CD56 positive), and epithelial differentiation (cytokeratin positive). This reflected the fact that ECTs probably arise from uncommitted ectomesenchymal cells that have the potential for multilineage differentiation. The immunohistochemical staining pattern observed for ECTs slightly differs from that of STMs. Strongly positive staining for GFAP and weakly positive staining for cytokeratin are observed in ECTs, whereas the opposite is typically observed for STMs. These findings indicated that the patterns of expression on immunohistochemistry differ between ECTs and STMs, although inevitably, there was some overlap. Thus, CD56 expression in the case presented here is noteworthy, and it could potentially become an adjunct diagnostic marker for ECT instead of previously used CD57.

Clinical, histological and immunohistochemical features of ectomesenchymal chondromyxoid tumor.

OBJECTIVE: Ectomesenchymal chondromyxoid tumor is a rare oral soft tissue neoplasm that should be differentiated from other neural and chondromyxoid entities. The aim of this study was to report the clinical, histological, and immunohistochemical features of 3 additional cases of this condition. METHODS: Clinical data were obtained from the clinical records and all cases were evaluated through light microscopy and immunohistochemistry to cytokeratins, vimentin, S100 protein, desmin, smooth muscle actin, and glial fibrilary acidic protein. RESULTS: All 3 cases affected the tongue as a long-lasting submucosal swelling and were managed through conservative surgery. They all showed myxoid and chondroid histological patterns, and vimentin, S100, and glial fibrilary acidic protein immunoexpression. CONCLUSIONS: These findings reinforce the typical features of ectomesenchymal chondromyxoid tumor previously described, helping to confirm and establish the clinical, histopathological, and immunohistochemical profile of this uncommon lesion.

[Immunohistochemical and ultrastructural heterogeneity of gastrointestinal stromal tumors]. / Hétérogénéité immunohistochimique et ultrastructurale des tumeurs stromales digestives.

AIMS AND METHODS: Digestive stromal tumors are the most frequent undifferentiated mesenchymal tumors. The prognosis of these tumors is difficult to predict and the histogenesis is still subject to controversy. However, the frequent and specific expression of CD117 (c-kit) by these tumors could suggest an origin from interstitial cells of Cajal. The aim of this study was to analyse the histological and immunohistochemical characteristics of 46 digestive stromal tumors surgically resected, with comparaison of CD34 and CD117 expression in these tumors. Sixteen tumors were analyzed on electron microscopy. RESULTS: Sixty three and 74% of the stromal tumors were positive for CD117 and CD34 respectively. While CD117 expression was similar in all locations, on the contrary, there was a decreasing gradient of CD34 expression between gastric (87%) and jejunal (33%) tumors. All tumors with skeinoid fibers expressed CD117. Focal expression of smooth muscle actin was noted in 43% of the cases. The ultrastructural study showed no correlation with the immunohistochemical results. CONCLUSION: Digestive stromal tumors show an immunophenotypic and ultrastructural heterogeneity. CD117 expression is frequent, but not constant.

Gastrointestinal stromal tumours.

Gastrointestinal stromal tumour (GIST) is the designation used here to identify the most common subset of gastrointestinal mesenchymal tumours specific to those sites. These tumours have unique histological, immunophenotypic and molecular genetic features that set them apart from typical smooth muscle tumours and schwannomas; however, by tradition, they have been classified as GI-smooth muscle tumours, or stromal tumours/smooth muscle tumours. GISTs occur predominantly in persons over 40 years of age with an equal sex incidence. Benign GISTs outnumber the malignant ones by a margin of 10:1. GISTs occur throughout the gastrointestinal tract, but are most common in the stomach (60-70%) and small intestine (30%). GISTs are rare in esophagus, colon and rectum. Histologically they may show a spindle cell or epithelioid pattern (the former largely corresponds with the designation of cellular leiomyoma and the latter with that of leiomyoblastoma). Immunohistochemically most GISTs are positive for CD34 and c-kit protein (CD117); the latter is quite specific for GISTs among mesenchymal tumours. Genetically GISTs commonly show DNA losses in the long arm of chromosome 14, and c-kit gene mutations occur at least in some cases. c-kit is also expressed in the interstitial cells of Cajal, the gastrointestinal pacemaker cells, and relationship of GISTs to these cells has been proposed recently. GISTs differ histologically, immunohistochemically and genetically from typical (esophageal) leiomyomas that are negative for c-kit and CD34 and neither show DNA-losses in 14q nor c-kit mutations. Evaluation of malignancy of GISTs is based on mitotic count, tumour size and extra-gastrointestinal spread. Tumours with mitotic counts higher than 5/10 high power fields or larger than 10 cm have a significant risk for recurrence and metastasis and are considered histologically malignant; however, some tumours with mitotic activity < 1/10HPF may metastasize indicating some uncertainty in malignant potential of GISTs, especially those larger than 5 cm.

[The clinicopathological and immunophenotypical features of 162 cases of gastrointestinal stromal tumor].

OBJECTIVE: To demonstrate the clinicopathological and immunophenotypical features of gastrointestinal stromal tumor (GIST). METHODS: One hundred and sixty-two cases of GIST were retrospectively studied. Among them, forty-six cases were immunostained using antibodies against vimentin, CD34, muscle specific actin (MSA), smooth muscle actin (SMA), neuron specific enolase(NSE), S-100 protein, synaptophysin (SYN), cytokeratin(CK), CEA, LCA. RESULTS: Clinically, male patients predominated with a male to female ratio of 3.8:1. The average age was 50 (range 6-74). The most common symptoms were gastrointestinal bleeding and abdominal mass in 45% and 39% of the cases, respectively. The common anatomical locations were stomach (43%), ileum (20%), jejunum (18%). Pathologically, all the tumor arose from the muscular layer. The tumor diameter varied from 0.5 to 43 cm. In 55% of the cases, the tumor was malignant. The main component cell types were spindle and epithelioid in appearance. Immunophenotypically, percentage of positivity for the 10 antibodies was as follows: vimentin, 100% (39/39), CD34, 64% (23/36), MSA, 47% (16/34), SMA, 41% (14/34), NSE, 61% (17/28), S-100 protein, 19% (4/21), SYN, 15% (3/20), CK, CEA, and LCA were negative. CONCLUSION: GIST is the most common mesenchymal tumor of the gastrointestinal tract. Immunostaining confirms that only some of the GIST shows partial differentiation toward smooth muscle, neuron, or both.

Appraisal of the comparative utility of immunohistochemistry and electron microscopy in the diagnosis of childhood round cell tumors.

To provide an objective assessment of the comparative utility of fluorescence- and peroxidase-based immunohistochemistry and electron microscopy, an observer blinded study was conducted under realistic study conditions utilizing a large sampling of poorly differentiated pediatric round cell tumors. Working independently, using a single ancillary technique of particular expertise, each of three investigators attempted to render a specific diagnosis with regard to 50 diagnostically challenging tumors. The results were compared against the subsequent "file diagnosis" established by consensus with all relevant information made available. A grading scheme was applied wherein points were awarded based on the accuracy and confidence of diagnosis. A comparative efficiency rating, expressed as a percentage, was formulated by dividing the number of points awarded each technique by the total number of points theoretically available. Electron microscopy proved superior overall, with an efficiency rating of 89%. Immunoperoxidase and immunofluorescence studies yielded efficiency ratings of 71 and 61%, respectively. Used in combination, the techniques achieved an efficiency rating of 95%. Application of these ancillary techniques resulted in a revision of the provisional diagnosis in 11 of 50 cases, and left only two cases without a firm specific diagnosis.

Malignant ectomesenchymoma in childhood.

Five childhood malignant ectomesenchymomas are reported from three centers in three countries. The children were all younger than 3 years (four less than 12 months), four were boys, and four tumors were sited in the pelvis or external genitalia. All tumors had distinctive light microscopic features of rhabdomyosarcoma and three also demonstrated small numbers of included neuronal cells. Immunohistochemical studies and transmission electron microscopy revealed the additional presence of neurogenic components in the remaining two patients. An additional epithelial component was found by immunohistochemistry in one tumor, which suggests a pluripotential origin that still requires karyotypic investigation. Aggressive chemotherapy and adequate surgical excision have thus far been effective in providing disease-free follow-up for periods of 7 to 50 months. It is implied that because the biological behavior and morphology closely resemble those of rhabdomyosarcoma and because the neurogenic component is often inconspicuous, many malignant ectomesenchymomas may be misdiagnosed as rhabdomyosarcomas.

CD34 expression by gastrointestinal tract stromal tumors.

Gastrointestinal stromal tumors (GISTs) are neoplasms arising in the wall of the gastrointestinal tract that frequently show evidence of smooth muscle differentiation, either by their appearance alone or by immunohistology. A significant number of these neoplasms fail to react with any markers of muscle differentiation, however. A subset of these neoplasms have epithelioid features, and the presence of these features can give rise to confusion with other neoplasms, such as carcinomas and melanomas. Here we show that the CD34 monoclonal antibody My10 reacts with 19 of 23 (83%) of these lesions, including both those with and without epithelioid features. Five of 10 epithelioid and one of 13 spindled neoplasms lacked detectable muscle-specific actin (MSA), smooth muscle actin (SMA), and desmin; all six were CD34 reactive. Immunoblotting experiments show that the antigen on these stromal neoplasms has a molecular weight identical to that found on hematopoietic cells. The frequency and intensity of the reactivity of GISTs with anti-CD34 antibodies are distinctly higher than those reported for smooth muscle neoplasms of soft tissue and myometrium. This reactivity can be a useful adjunct in the diagnosis of difficult cases, especially in those exhibiting epithelioid morphology.

Expression of Ki-1 antigen (CD30) in mesenchymal tumors.

Expression of CD30(Ki-1) antigen has long been considered to be restricted to activated lymphocytes and related tumors. However, expression of this antigen has also been detected in embryonal carcinomas, in nonembryonal carcinomas, in malignant melanomas, and even in some myeloid cell lines and macrophages at late stages of differentiation. In this study, using monoclonal antibody Ki-1, expression of CD30 antigen was immunohistochemically examined in frozen sections of 28 benign and 63 malignant mesenchymal tumors. The authors found CD30 expressed in two of four leiomyomas, seven of 11 leiomysarcomas, one of six rhabdomyosarcomas, two of two aggressive fibromatoses, one of three fibrosarcomas, two of four synovial sarcomas, one giant cell tumors of tendon sheaths, all five malignant fibrous histiocytomas, all three osteosarcomas, one of three Ewing's sarcomas, in a tumor cell subpopulation of two of ten malignant schwannomas, and in the Schwann cell compartment of one of two ganglioneuromas tested. Furthermore, CD30 was consistently expressed in the myoepithelial compartment of 13 fibroadenomas. However, all five lipomas, all seven liposarcomas, all three neuroblastomas, both ganglioneuroblastomas, both chondrosarcomas, and tumors of disputed origin tested were consistently CD30 negative. These findings indicate that, outside the lymphatic system, CD30 antigen is not restricted to epithelial neoplasms but may also be present in tumors of mesenchymal origin. The authors conclude that CD30 antigen, although having limited utility in the differential diagnosis of tumors of questionable histogenesis, may eventually define relevant subgroups within the main tumor categories.

Undifferentiated (embryonal) sarcoma of the liver: ultrastructure, immunohistochemistry, and DNA ploidy analysis of two cases.

We describe the histopathologic, immunohistochemical, electronmicroscopic features, and DNA flow cytometric analysis of 2 cases of undifferentiated (embryonal) sarcoma of the liver. The tumor cells were found to be uniformly nonreactive to antibodies that identify cells belonging to the macrophagic-monocytic system. Focal expression of cytokeratin was an unexpected finding. We conclude that the observations are compatible with origin of this sarcoma from primitive mesenchyme. Uncertainty still exists about histogenesis, but the morphologic features of this neoplasm are quite characteristic. Both tumors demonstrate aneuploid stem lines with high S phase. Whether these findings are prognostically significant remains to be seen.

Expression of the common acute lymphoblastic leukemia antigen (CD10) in mesenchymal tumors.

The expression of the CD10 antigen, formerly designated as common acute lymphoblastic leukemia antigen and recently identified as neutral endopeptidase, was examined immunohistochemically in 26 benign and in 55 malignant mesenchymal tumors. CD10 expression was found in 4 of 4 leiomyomas, 7 of 10 leiomyosarcomas, 1 of 6 rhabdomyosarcomas, 2 of 2 Triton tumors, 1 of 2 aggressive fibromatoses, 1 of 3 fibrosarcomas, 1 of 4 synovial sarcomas, 1 of 1 giant cell tumors of tendon sheath, 4 of 4 malignant fibrous histiocytomas, 3 of 3 Ewing's sarcomas, and 2 of 3 osteosarcomas. Furthermore, CD10 was expressed consistently in the myoepithelial compartment of 12 fibroadenomas and, in 7 of these cases, in a minor stromal cell population, probably of (myo-) fibroblastic origin. Tumors of adipose tissue (4 lipomas, 5 liposarcomas), tumors of autonomic ganglia (2 ganglioneuromas, 1 ganglioneuroblastoma, 2 neuroblastomas), tumors of peripheral nerves with purely schwannian differentiation (7 malignant schwannomas), and tumors of disputed origin were consistently CD10-negative, however, as were single cases of fibroma and chondrosarcoma. These findings indicate that the expression of CD10 is a frequent but not obligatory feature in some mesenchymal tumors. Therefore CD10 is of value in the differential diagnosis of mesenchymal tumors.

Pulmonary blastoma. An ultrastructural study of a case and its transplanted tumor in athymic nude mice.

A pulmonary blastoma in a 52-year-old Japanese man was serially transplanted into athymic nude mice. This report emphasizes the characteristics of the neoplasm seen on light and electron microscopic examination. The original tumor consisted of branching tubular structures and primitive mesenchymal components with a few smooth-muscle cell bundles, and resembled fetal lung tissue. Electron microscopic examination revealed that the immature stromal cells resembled epithelial cells. After serial passages in nude mice, the stromal element of the tumor disappeared, and the epithelial element showed squamous metaplasia and occasional mucus production. Endocrine-type granules were observed in a few tumor cells. Histogenetic considerations, including a suggestion that the tumor was derived from entodermal cells, are presented.