Novel epitheliomesenchymal biphasic stomach tumour (gastroblastoma) in a 9-year-old: morphological, ultrastructural and immunohistochemical findings.

Gastroblastoma is a rare gastric epitheliomesenchymal biphasic tumour composed of spindle and epithelial cells, reported by Miettinen et al in a series of three cases in 2009. All those cases arose in stomachs of young adults. Neither the epithelial nor the mesenchymal component displayed sufficient atypia to diagnose a carcinosarcoma or other malignancy. On immunohistochemistry, the epithelial component expressed cytokeratin, and the mesenchymal component was positive for vimentin and CD10. Miettinen et al designated these neoplasms as gastroblastomas based on their similarities with other childhood blastomas such as pleuropulmonary blastoma and nephroblastoma. This report describes a probable fourth case of this unique type of neoplasm. The present case arose in the gastric antrum of a 9-year-old boy. While similarities were evident with the other cases, there were some differences. The epithelial component was more predominant and showed more mature morphology. Immunohistochemically, the epithelial component showed immunolabelling for c-KIT and CD56. The mesenchymal component was only focally positive for CD10. Ultrastructually, desmosomes and microvilli were found supporting a truly epithelial lesion.

The epithelial-mesenchymal transition promotes transdifferentiation of subcutaneously implanted hepatic oval cells into mesenchymal tumor tissue.

Hepatic oval cells are thought to represent facultative hepatic epithelial stem cells in liver in which damage inhibits hepatocyte proliferation and liver regeneration. The LE/6 hepatic stem cell line was derived from the liver of male Sprague-Dawley rats fed a choline-deficient diet containing 0.1% ethionine. They are histochemically characterized by their expression of hepatocytic (hepPar1), cholangiocytic cytokeratin (CK19), hepatic progenitor cell (OV-6), and hematopoietic stem cell (c-kit) markers. In this study, we transplanted LE/6 cells by subcutaneous injection into adult female nude mice, and examined their engraftment and differentiation potential in the subcutaneous microenvironment in vivo. Our results demonstrated that following subcutaneous transplantation, differentiation of LE/6 cells into mesenchymal tumor tissue (MTT) was associated with reduced E-cadherin expression, upregulation of E-cadherin repressor molecules (Snail proteins), and increased expression of vimentin and N-cadherin, all of these events are characteristic of the epithelial-mesenchymal transition (EMT).

Undifferentiated perivascular cells in myxoid mesenchymal tumors: an ultrastructural study.

The current WHO classification of soft tissue tumors is based on the lineage of differentiation of the proliferating cells. Since mature mesenchymal cells have a broad phenotypic plasticity it has been considered unnecessary to recur to a hypothetical stem cell to explain the origin of these neoplasms. In spite of this assumption, the target cell of the oncogenic mutations in mesenchymal tumors is still a controversial item. Myxoid mesenchymal tumors constitute a heterogeneous group of neoplasms sharing in an ample mucinous matrix that separates neoplastic cells and facilitates their single submicroscopic study under electron microscopy examination. The authors have studied, by electron microscopy, 74 myxoid mesenchymal tumors, including a large variety of nosologic entities, to assess their madurational gradient. In 43 of 74 cases, a common element has been found: medium-sized cells, with high nucleo-cytoplasmic ratio, lacking lineage specific features, which were arranged around the capillary vessels. In some cases, the authors were able to demonstrate gradual differentiation in these cells, as they moved away from the vessels. These features support the hypothesis that at least some mesenchymal tumors originate from perivascular undifferentiated cells. In addition, the findings might contribute to define both topographic and morphologic characteristics of adult stem mesenchymal cells.

Phosphaturic mesenchymal tumor (mixed connective tissue variant): a case report with spectral analysis.

We present a further case of a rare mesenchymal neoplasm termed phosphaturic mesenchymal tumor (mixed connective tissue variant). The patient was a 42-year-old man with a long history of osteomalacia of unknown etiology with pathological bone fracture, abnormality of parathyroid glands, kyphosis, scoliosis, and spondylosis. Laboratory investigation disclosed hypophosphatemia, elevated serum alkaline phosphatase activity, and normal serum calcium level. The patient had a soft tissue mass in the right inguinal area, measuring 11 x 6 x 5 cm, which was previously interpreted as a calcified hematoma on sonography. The tumor was surgically removed. Grossly, the tumor was well circumscribed, unencapsulated, and had soft to dense consistency. The cut surface had a variegated appearance due to the presence of large hemorrhagic areas admixed with foci of grey-yellow tissue. Histologically, the tumor was composed of primitive mesenchymal cells, osteoclast-like cells, and cells showing myofibroblastic features without cytologic atypia. There were a well developed vascular network, microcystic areas, and poorly formed cartilaginous foci. Unusual and hitherto unpublished prominent features were flower-like, slate-gray crystals, widespread hemosiderin deposits and large areas of hemorrhages, with the latter comprising approximately 60% of the tumor. A spectral analysis indicated that chemically, the crystals mainly consisted of calcium phosphate and sodium nitrate.

Mixed neuronal-glial tumor of the digestive tract: distinctive entity from gastrointestinal stromal tumor?

A 53-year-old-woman presenting with pelvic discomfort was found to have a 9.5 cm tumor located in the wall of the ileon. Light microscopy showed that the tumor was made of fascicles of plump spindle cells and bizarre epithelioid cells. A cuff of lymphoid cells was also present at the tumor margin. The tumor cells strongly expressed tau protein, neuron-specific enolase, protein green product 9.5 and glial fibrillary acid protein (GFAP), but did not show positive immunostaining for S-100 protein, CD34 or CD117. The tumor showed unequivocal ultrastructural evidence of neural differentiation. Skeinoid fibers were scattered throughout the tumor. This is the first mixed neuronal-glial tumor of the digestive tract to be described in the literature. Such histological and immunohistochemical features could be misinterpreted as features of digestive schwannoma. We suggest that this tumor is distinct from gastrointestinal stromal tumors in lacking CD34 and CD117 expression.

[Giant mesenchymal tumor of the vulva with atypical clinical evolution]. / Tumor mesenquinmatoso gigante de la vulva con comportamiento clínico atípico.

Mixed mesenchymal tumors of the vulva are rare lesions. On other hand, aggressive angiomyxoma is a recently characterized neoplasm occurring principally in the pelvic soft-tissues and showing propensity for local recurrence. The benign soft-tissue tumors are small than malign neoplasm, mimicking and often are misdiagnosed as cysts of Bartholin's gland. In this report we describe one case of a benign, giant and atypical mixed mesenchymal tumor of the vulva and its particular clinical characteristics.

Tumor mesenquimatoso gigante de la vulva con comportamiento clínico atípico / A giant mesenchymal tumor of the vulva showing atypical clinical crolotion. Clinical report

Los tumores del mesénquima de la vulva son poco frecuentes. Por otra parte, el angiomixoma de comportamiento clínico agresivo es una lesión recientemente caracterizada que se presenta principalmente en los tejidos blandos de la pelvis y tiene tendencia a recurrir localmente. Las variedades benignas suelen ser de dimensiones menores y generalmente se confunden con quistes de la glándula de Bartholin. En este trabajo se describe el caso de un tumor mesenquimatoso mixto gigante y benigno de la vulva con características clínicas atípicas

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.

[Myofibroblastoma of the lymph nodes]. / A nyirokcsomó myofibroblastomája.

We report a case of intranodal myofibroblastoma occurring in a lymph node of the left inguinal region of a 53 years old female. This tumor was first described 6 years ago and has not been yet documented in the Hungarian literature. This rare benign mesenchymal neoplasm of the lymph node occurs almost exclusively in the inguinal region. Histologically the tumor is characterized by interlacing fascicles of spindle cells which show nuclear palisading and the presence of hemorrhage. Immunohistochemically, the tumor cells were positive for actin and vimentin. Electronmicroscopic investigation demonstrated features characteristic for myofibroblastic origin. Characteristic amianthoid structures were occasionally present. It is important to distinguish this tumor entity of other primary or secondary mesenchymal neoplasms of lymph nodes including nodal involvement of Kaposi's sarcoma, a lesion it may closely resemble.

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.

Panuveal malignant mesenchymoma.

Intraocular malignant mesenchymal tumors are very rare, and only a few case reports of such primary and metastatic tumors have been reported. We report a case of a malignant mesenchymoma involving the entire uveal tract. A 21-year-old woman presented with a tumor on the whole iris of the right eye, which caused intractable glaucoma. Upon enucleation of the eye, a very anaplastic tumor was found to occupy the whole uveal tract; its features were compatible with a tumor of mesenchymal origin, including rhabdomyosarcomatous and liposarcomatous characteristics. Choroidal osteoma was a coincidental finding. The histologic findings of the tumor were of two types of malignant mesenchymal tumors, and therefore the diagnosis of malignant mesenchymoma was made. This is to our knowledge the first tumor of its kind to be reported intraocularly.

Cutaneous mesenchymal tumour with haemangiopericytoma-like features.

A case of cutaneous mesenchymal haemangiopericytoma-like tumour affecting a 17-year-old male is presented. Clinical features were non-specific. The tumour was studied by light, electron microscopy and immunohistochemistry. The results of these studies suggested the diagnosis of a mesenchymal, poorly-differentiated tumour showing features of haemangiopericytoma. The clinical course after surgery was uneventful after a 9-month follow-up period.

Spindle cell variants of embryonal rhabdomyosarcoma in the paratesticular region. A report of the Intergroup Rhabdomyosarcoma Study.

We reviewed 173 cases of paratesticular rhabdomyosarcoma (RMS) of Intergroup Rhabdomyosarcoma Studies (IRS)-I, -II, and -III for evaluation of possible histological factors that might account for the good prognosis of these patients. Almost all cases (161 of 173 cases, 93.1%) occurring in this site were of embryonal histology. A spindle-cell subtype of embryonal RMS was identified that presented a storiform growth pattern with abundant collagen between the tumor cells in most cases. Other tumors of this subtype showed an arrangement of tumor cells in bundles with a low to moderate amount of collagen, resembling a leiomyosarcoma. The other embryonal RMS in this site had the classical embryonal cytology. The spindle-cell subtype was highly differentiated by immunohistochemistry and electron microscopy. Lymph node metastasis was found in seven of 43 patients (16.3%) with a RMS of spindle-cell subtype, compared with 40 of 112 patients (35.7%) with RMS of non-spindle-cell type. Clinical data from patients with spindle-cell subtypes of the paratesticular lesions revealed that they almost always had an association with clinical groups of limited disease (32 patients, 74.4%, with Group I; 10 patients, 23.3%, with Group II disease) and a significantly better prognosis (95.5% survival at 5 years) when compared with patients with the classic embryonal variant of RMS (80% survival at 5 years, p < 0.035). The incidence and anatomic distribution of this spindle cell subtype of embryonal RMS was estimated on 800 randomly selected patients from IRS-II. It was found in the head and neck, extremities, orbit, and some other sites, but 30.6% were located in the paratesticular area. Patients with spindle cell RMS of nonparatesticular sites usually had more extensive disease compared with patients having paratesticular lesions; two thirds of the cases had gross residual tumor after surgery or metastatic tumor at diagnosis. We conclude that spindle-cell RMS is a subtype of embryonal RMS with a very favorable prognosis. The site factor of the paratesticular localization may allow earlier diagnosis of the spindle-cell lesions compared with other sites. Other unknown factors may also play a role.

Uncommon mesenchymal tumors of the liver. Light microscopy, ultrastructure, immunohistochemistry and literature review.

This report presents the gross morphology, cytological, histological, ultrastructural and immunohistochemical features of two angiomyelolipomas of the liver. Diagnosis and classification of these tumors is difficult. There is no immunohistochemical and ultrastructural confirmation for Ito-cell pathogenesis of hepatic angiomyelolipomas.

[Application of electron microscopy in the diagnosis of neoplasms].

The majority of neoplasms can be diagnosed by light microscopy, but in some cases the diagnosis remains ambiguous due to poor differentiation, even though special stainings have been employed. This paper presents 34 cases of neoplasms in which the tumors were diagnosed by electron microscopy. This includes distinguishing (1) anaplastic carcinoma from lymphoma; (2) anaplastic carcinoma from amelanotic melanoma; (3) APUDoma from other tumors; (4) different mesenchymal tumors. The diagnoses of 4 cases of malignant melanoma, 11 cases of APUDoma, 7 cases of poorly differentiated carcinoma or anaplastic carcinoma, 2 cases of non-Hodgkin's lymphoma, 9 cases of mesenchymal tumors and 1 cases of other tumors have been resolved by electron microscopy. It is obvious that in some cases, electron microscopy can be of help in establishing a correct diagnosis.

Primary malignant ectomesenchymoma of the orbit.

Malignant ectomesenchymoma (MEM) is a rare soft tissue tumour believed to arise from a pluripotential migratory neural crest cell and composed of both a mesenchymal element (most often rhabdomyosarcoma) and a neuroectodermal element (often neuroblastoma). Reported sites of origin are the abdomen, perineum or scrotum, the extremities, the middle ear, nasopharynx, face, and neck. We report the first case of an orbital MEM, with a review of the 17 cases previously reported from other sites.

Immunohistochemical and ultrastructural spectrum of hepatic sarcomas of childhood: evidence for a common histogenesis.

Hepatic sarcomas of childhood, which appear heterogeneous by standard morphologic criteria, pose challenging diagnostic and nosologic problems to the pediatric surgical pathologist. To identify features of these tumors that might help to clarify their origin and histologic classification, we studied 13 undifferentiated (embryonal) sarcomas of the liver (UESL) and two intrinsic hepatic rhabdomyosarcomas (RMS) using immunohistochemical and electron microscopic techniques. Immunohistochemical staining was performed on 14 tumors with use of commercially available antibodies against a variety of markers, as well as peanut agglutinin lectin; electron microscopy was performed on five UESL and both RMS. Desmin was expressed by 6/12 UESL and 2/2 RMS, muscle-specific actin by 5/12 UESL and 2/2 RMS, neuron-specific enolase by 1/12 UESL and 1/2 RMS, alpha-1-antitrypsin by 8/12 UESL and 1/2 RMS, and alpha-1-antichymotrypsin by 10/12 UESL and 1/2 RMS. Cytokeratin expression was observed in only four UESL. The overlap of immunohistochemical staining patterns and ultrastructural features shown by these obstensibly different tumors suggests a common histogenesis, perhaps from a multipotential mesenchymal stem cell.

Distinctive unclassified mesenchymal tumor of the digit of dogs.

Four examples of a mesenchymal tumor of undetermined histogenesis occurred in three mixed-breed dogs and one Yorkshire terrier. All tumors occurred as solitary, soft to firm, solid, tan, and ulcerated masses in the digits of dogs aged 11 to 15 years. The compact cellular tumor had cells with anisokaryotic round, oval, or irregular nuclei, some of which were multinucleated. The neoplastic cells appeared to arise in the tissue near the third phalanx in the area of dense collagenous trabeculae located proximal to the fat pad and sweat glands. The unclassifiable cells had some features of histiocytes by transmission electron microscopy, but failed to stain for lysozyme and alpha-1-antichymotrypsin, markers for monocyte-macrophage derived cells. Immunohistochemically, the cells stained for vimentin but not for cytokeratins, desmin, S-100 protein, epithelial membrane antigen, alpha-lactalbumin, lysozyme, alpha-1-antichymotrypsin, alpha-lactalbumin, casein, and heavy and light chain immunoglobulins. The combined findings of light and transmission electron microscopy and immunohistochemistry exclude tumor histogenesis from an epithelial cell, melanocyte, mast cell, plasma cell, Schwann cells, and Merkel cell.

Undifferentiated (embryonal) sarcoma of the liver. A tumor of uncertain histogenesis showing divergent differentiation.

Pathologic features of eight cases of undifferentiated (embryonal) sarcoma of the liver (USL) in childhood were studied. Light microscopic examination showed a diffuse growth of spindle cells with occasional polygonal cells and multinucleated giant cells and also revealed focal areas of storiform pattern in four tumors, cambium layer formation in one tumor, and alveolar arrangement in one tumor. Immunohistochemical study showed positive staining of proliferating cells for suggestive histiocytic markers (A1AT in 6/6, A1ACT in 5/6, lysozyme in 4/6, and KP1 in 4/6) and for muscle markers (desmin in 4/6 and HHF35 in 3/6). Ultrastructural examination demonstrated that the individual tumors were composed of a mixture of cells having fibroblastic, histiocytoid, fibrohistiocytoid, myofibroblastic, and undifferentiated (primitive mesenchymal) morphologies. Also identified were cells with definite myoblastic morphology in three tumors: leiomyoblastic in one and rhabdomyoblastic in two. In conclusion, the tumor cells in USL show phenotypical diversity comparable to those of malignant fibrous histiocytoma with or without additional rhabdomyosarcomatous or leiomyosarcomatous differentiation.