Alveolar soft part sarcoma: clinical, histopathological, molecular, and ultrastructural aspects

Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor occurring mainly in the adolescents and young adults. Multimodality treatment has not been effective, and excision remains the mainstay of treatment. Histopathologically, it varies little from case to case. It is composed of organoid aggregates of large polygonal cells with vesicular nuclei and abundant granular, eosinophilic cytoplasm, separated by delicate vascular channels. The line of differentiation of this unique tumor is yet undetermined, although recent advances have led to a better understanding of the genetic events underlying the pathogenesis of this tumor. The histopathological, ultrastructural, immunohistochemical, and genetic aspects of ASPS are discussed.     

Eosinophilic granuloma with acute epidural hematoma: a case report.

The most common symptoms of eosinophilic granuloma are local tenderness and an enlarged skull mass. The presence of epidural hematoma is a very rare symptom of eosinophilic granuloma. To our knowledge, this is only the second reported case of eosinophilic granuloma with epidural hematoma. A 2-year-old boy with a soft tumor on the occipital scalp, palpable at the age of 3 months, yet with no obvious history of trauma, was admitted due to a sudden onset of loss of consciousness. A brain computed tomography scan showed a lytic lesion on the occipital skull with a large epidural and subcutaneous hematoma, causing brain compression. He underwent an emergency craniectomy with removal of both the tumor and hematoma. The patient regained consciousness and had no residual neurological damage. Pathological reports showed abnormal proliferation of Langerhans' cells, eosinophilic cells and multinucleated cells. A whole-body bone nuclide scan revealed no other bone lesions. The patient was discharged uneventfully. The causes of hematomas are not very clear. They may be due to tumor necrosis or minor trauma. In our presented case, the cause of the epidural hematoma may have been tumor bleeding which ruptured into the epidural space. A solitary eosinophilic granuloma of the skull with acute epidural hematoma and loss of consciousness is extremely uncommon. Craniectomy with removal of the tumor and hematoma decompression may produce good results.     

Congenital Generalized Myofibromatosis: A Disseminated Angiocentric Myofibromatosis

Infantile myofibromatosis occurs in solitary, multiple, and generalized forms, with similar histology but different clinicopathologic and prognostic implications. We report the findings in two male infants with fatal congenital generalized myofibromatosis (CGMF) who presented with multiple dermal and subcutaneous nodules at birth. Imaging studies revealed bony and visceral lesions, which progressed despite chemotherapy. One infant had severe hypercalcemia associated with extensive lytic bone lesions. Both infants died in respiratory failure and had a combination of pulmonary CGMF and diffuse alveolar damage. Involvement of skin, soft tissue, bone, heart, lungs, liver, gastrointestinal tract, and endocrine organs was confirmed at autopsy in each case. A consistent histologic pattern of interlacing fascicles of myofibroblasts with abundant eosinophilic cytoplasm was noted, with variable necrosis and calcifications in some sites. The myofibroblasts displayed vimentin and smooth muscle actin immunoreactivity. The lungs in each case had the presumably early lesions of CGMF with an angiocentric and perivascular growth of myofibroblasts. A similar vascular pattern was present in all affected organs. These two cases demonstrate the extraordinary presentation of CGMF, which suggests its multifocal origin from vascular subintimal mesenchymal or smooth muscle cells whose phenotype is that of myofibroblasts.     

Alveolar soft part sarcoma occurring on the abdominal wall of a 2-year-old child

Alveolar soft part sarcoma (ASPS) is a rare soft tissue malignant neoplasm that affects young people. It can occur in any region of the body and at any stage of development. But ASPS on the abdominal wall is rarely reported. However, a few cases were reported in children under the age of 10 years. In this study we report a case of ASPS that occurred on the abdominal wall of a 2-year-old patient.     

Massive bone marrow involvement by clear cell variant of rhabdomyosarcoma

A 16-year-old boy with generalized myalgia and petechial hemorrhage was found to have a diffuse infiltrative disease in his bone marrow (BM). The BM aspirate contained a dense population of vacuolated blast-like cells. The BM biopsy displayed compact sheets of small round cells with clear cytoplasm, reminiscent of Ewing sarcoma. Immunostains were not diagnostically conclusive while transmission electron microscopy on the BM cells demonstrated a clear skeletal muscle differentiation. The morphologic findings led to a tentative designation of metastatic embryonal rhabdomyosarcoma (RMS). It was not until cytogenetic analysis revealed the specific translocation t(2;13)(q35;q14) did the alveolar RMS finally get confirmed. Despite an exhaustive search by imaging studies, a primary tumor was not detected. This case illustrates that the massive BM involvement by atypical alveolar RMS of unknown origin may pose serious diagnostic challenges. Multidisciplinary studies are required to reach a definitive diagnosis     

Expression of Early and Late Adenoviral Proteins in Fatal Adenovirus Bronchopneumonia

The localization and distribution of three adenoviral proteins, hexon, E1 A, and 55-kDaE1B, in 16 cases of fatal adenovirus bronchopneumonia in infants and children, are described. The proteins were immunohistochemically demonstrated in paraffin sections using monoclonal antibodies followed by the avidin-biotin-peroxidase method. The hexon antigen was present in inclusion-bearing bronchial, bronchiolar, and alveolar cells, mainly in the so-called rosette cells, as well as in necrotic debris in necrotizing areas. E1A antigen was also recognized in cells with nuclear inclusions where the reaction decorated the inclusion, nuclear chromatin, and cytoplasm but distributed mainly in alveolar cells and to a lesser extent in bronchial and bronchiolar cells. The 55-kDa E1B protein was extensively present in “activated,” reactive-appearing, nuclei of bronchial, bronchiolar, and alveolar epithelial cells and in the cytoplasm of rare cells having nuclear inclusions. These activated nuclei did not stain for the other two antigens. “Smudge” cells reacted poorly or not at all with any of the antibodies. The reactivity found produced a sort of complementary pattern between the hexon-positive, inclusion-containing cells and the 55-kDa E1B-positive, inclusion-noncontaining cells. The relationships of present findings and uirologic data are discussed.     

Congenital epulis of the jaw: a series of five cases and review of literature

This article describes five cases of congenital epulis, a rare and benign swelling in the mouth of a newborn, which is not widely known. We present five cases: four cases presented as single pedunculated nodules of the gingiva and in one case two nodules were present. Of all, 50% were located at the maxilla. Excision was performed in four of the five cases and in one case, spontaneous regression was awaited. No recurrence was reported. The characteristic features of congenital epulis are a pedunculated, flesh-pink coloured tumour with a predominant occurrence on the anterior maxillary alveolar ridge in a female newborn. Although the aetiology is unknown, most authors suggest a mesenchymal, rather than an odontogenic, origin. Endogenous hormonal factors might influence growth prenatally. Histological findings include granular cells with eosinophilic cytoplasm and small, eccentric nuclei. Despite the fact that the lesion can be a striking sight, spontaneous regression is possible and can be awaited. Indications for non-radical excision under local anaesthesia are severe upper airway obstruction and interference with feeding technique. In conclusion, we provide clinical and histological information about congenital epulis, so that this entity will be more easily recognised and relevant information given to parents.     

PULMONARY ENDODERMAL TUMOR RESEMBLING FETAL LUNG: Report of a Case in a 14-Year-Old Girl

This report describes the clinical and histologic features of a pulmonary tumor in a 14-year-old girl that is most consistent with a rare entity described in the literature as "pulmonary endodermal tumor resembling fetal lung" (PET). This tumor is composed of glycogen-rich columnar cells forming complex glands with focal festooning and mitotic activity, admixed with solid "morules" of cells with eosinophilic cytoplasm and focal nuclear clearing. Patchy tumor necrosis and a bland stroma were also present. Immunoreactivity for carcinoembryonic antigen (CEA), alpha -antichymotrypsin, and 12E7 1 was present in glandular cells and for human chorionic gondatropin (HCG), alpha -antichymotrypsin, 1 and 12E7 in morular cells. Ultrastructural features are those of an epithelial tumor. Related entities have been called "pulmonary blastoma lacking sarcomatous elements" and "adenocarcinoma of fetal lung type." Most cases of PET have occurred in adults, and the histologic features thought to have prognostic significance in small published series are applied to our case, in which the patient remains well and without evidence of tumor recurrence or metastasis for 28 months following local resection as the sole treatment.     

Giant Cell Tumor of Soft Tissue with Pulmonary Metastases: Pathologic and Cytogenetic Study

Giant cell tumor of soft tissue (GCTST) has gained general acceptance as an uncommon but distinct primary soft tissue tumor since it was first described in 1972. GCTST is predominantly seen in adults and typically shows uniformly dispersed osteoclast-like giant cells admixed with oval to polygonal mononuclear cells. It usually follows a benign clinical course, although the malignant variant has been described in cases in which the mononuclear cells demonstrate obvious dysplastic features. It is still not clear whether the two variants belong to the spectrum of the same tumor. No cytogenetic chromosomal abnormalities have been reported in the literature of GCTST. Interestingly, the osseous counterpart of giant cell tumor, which shares similar histologic features, quite often displays a telomeric association at the cytogenetic level, a finding that has never been reported in GCTST. We report the case of a 12-year-old girl with GCTST of the right leg that metastasized to the lung. Cytogenetic studies from the primary tumor showed the phenomenon of telomeric association involving multiple chromosomes.     

Mesenchymal chondrosarcoma of the foot,an unusual location: Case report and review of the literature

We present a case of primary mesenchymal chondrosarcoma of the proximal phalanx of the first toe. The bones of the foot represent an infrequent primary site for this neoplasm. The tumour consisted of layers of undifferentiated round cells with scanty cytoplasm and hyperchromatic nuclei. The presence of brain, lung, and left auricle metastasis was demonstrated, and the patient died due to brain edema 18 days after admission. Mesenchymal chondrosarcoma is a rare tumor that more frequently involves the pelvic bones, the femur, and the humerus. To our knowledge, only nine cases of primary mesenchymal chondrosarcoma arising from the bones of the foot have been previously reported, with none involving the phalanx of the toe. © 1996 Wiley-Liss, Inc.     

Primary leptomeningeal histiocytic lymphoma in a young child

A 20-month-old boy had an 8-week history of vomiting, lethargy, generalized muscle weakness, and seizures. There was no history or clinical signs of an underlying systemic disease or an immunodeficiency. Cerebrospinal fluid (CSF) had 99 nucleated cells/cu mm, malignant cells, high protein and normal glucose. CT and MRI scans showed diffuse meningeal enhancement around the brain and spinal cord, but no parenchymal involvement. Biopsy of the leptomeninges showed malignant cells with marked nuclear pleomorphism and prominent clear to eosinophilic cytoplasm. The immunohistochemical studies were positive for histiocyte-macrophage markers and were negative with T and B cells, Ki-1, neural and glial cell antibodies. Multiple tests revealed no other site of disease. The patient died 3 months after onset of treatment despite intensive IV and intrathecal chemotherapy. We have not found any other reported case of primary histiocytic leptomeningeal lymphoma in a young child. © 1996 Wiley-Liss, Inc.     

Third ventricular chordoid meningioma in a child

Meningiomas are rare in children. Chordoid meningioma is a very rare variant, as only 16 cases in children have been reported. The authors report the first case of a chordoid meningioma in the third ventricle. A 12-year-old boy presented with headache, abnormal behaviors, and ataxia. Brain MR imaging revealed a 2-cm, well-enhanced mass in the third ventricle and hydrocephalus. Positron emission tomography with [18F]fluorodeoxyglucose showed that the mass was hypermetabolic. Gross-total removal of the mass was performed using a left frontal transcortical and transventricular approach. The mass originated from the left caudate head and was connected to the choroid plexus. A chordoid meningioma was diagnosed on the basis of the histological characteristics of the tumor, which was composed of cords and nests of eosinophilic vacuolated cells with an abundant myxoid matrix, similar to the features of a chordoma. A typical focal meningiomatous pattern was observed. The tumor cells were immunoreactive for vimentin and epithelial membrane antigen. The patient's headache and gait disturbance improved after the tumor was removed. The tumor showed no signs of recurrence during 12 months of follow-up.     

Splenic involvement in a stillborn fetus with tuberous sclerosis and multiple cardiac rhabdomyomas

Multiple cardiac rhabdomyomas are frequently associated with tuberous sclerosis (TSC). However, splenic involvement in TSC is very rare. Histiocytoid cells in the spleen have been previously reported in only seven neonates and one fetus. We report an unusual case of multiple cardiac rhabdomyomas in a stillborn fetus with TSC who had clusters of histiocytoid cells in the spleen. These large cells had abundant eosinophilic cytoplasm and were positive with CD 68; ultrastructurally, they contained many membrane-bound bodies. It has been suggested that these cells are histiocytes. To the best of our knowledge, the present case is the second stillborn fetus who had splenic involvement with TSC.     

GENE ALTERATIONS AND APOPTOSIS IN RHABDOMYOSARCOMA

The aim of the study is to look retrospectively for gene alterations and evaluate apoptosis in rhabdomyosarcomas RMSs from 40 children including 24 patients not previously treated. Histological subtype was botryoid in 1 case, spindle cell in 2 cases, embryonal in 22 cases, alveolar in 10 cases, and undetermined in 5 cases. Gene expression was evaluated immunohistochemically for p53 tumor suppressor gene, MDM2 oncogene, and bcl-2 gene. N-myc amplification was detected by in situ hybridization. Apoptotic cells and bodies were recognized morphologically and stained by 3-OH end labeling. Intranuclear accumulation of p53 protein was obvious 25 of tumor cells in two recurrent embryonal RMSs. Expression of the MDM2 gene was intense 80 of tumor cells in a recurrent and metastatic embryonal RMS. Amplification of the N-myc gene was obvious about 20 of tumor cells in an alveolar RMS metastatic at diagnosis. Expression of the bcl-2 gene was intermediate 25-75 of tumor cells in 26 of cases and high 75 of tumor cells in 10 of cases either embryonal or alveolar. The percentage of tumor cells showing morphologically recognizable apoptosis was 0.2-7.5 mean 2.9 . There was no correlation between apoptosis and histological subtype, bcl-2 expression, or previous treatment.     

Extracellular Matrix of Small Round cell Tumors of Childhood: An Immunohistochemical Study of 67 Cases

Sixty-seven childhood tumors were studied immunohistochemically for the extracellular matrix elements type IV collagen, laminin, and fibronectin. Tumors included Ewing's sarcoma, primitive neuroectodermal tumor, small cell osteosarcoma, neuroblastoma or ganglioneuroblastoma, rhabdomyosarcoma, and lymphoma. It was found that small cell osteosarcoma was often positive for fibronectin but not type IV collagen or laminin, a new observation. In the lymphomas, matrix proteins were rarely found. Ewing's sarcoma was variably positive for type IV collagen and laminin, but fibronectin was absent. Extracellular laminin and fibronectin were found in one of two cases of primitive neuroectodermal tumor. In neuroblastoma and ganglioneuroblastoma, the matrix components were rarely found. These results, discrepant with findings in cultured cells, may reflect the altered capacity of tumors to produce these proteins in vitro, which suggests that caution should be exercised in drawing conclusions regarding the nature or histogenesis of tumors from data obtained with cultured tumor cells. Embryonal rhabdomyosarcoma frequently contained all matrix elements in the extracellular space and in a dotlike pattern in the cytoplasm; alveolar rhabdomyosarcoma rarely contained these proteins and never exhibited the dotlike pattern. The frequent finding of matrix proteins in embryonal rhabdomyosarcoma but only rarely in alveolar rhabdomyosarcoma and the unique immunostaining pattern in embryonal rhabdomyosarcoma may prove to be a useful adjunct in the diagnosis of childhood tumors.     

LYMPHOKINES POST AUTOLOGOUS PERIPHERAL BLOOD STEM CELL TRANSPLANTATION IN CHILDREN

Malignant ectomesenchymoma (MEM) is a rare soft tissue tumor believed to arise from a pluripotent migratory neural crest cell and composed of both a mesenchymal element and a neuroectodermal element. The authors report the case of an 11-month-old male who presented with a local abdominal MEM and systemic metastases into lungs, liver, bones, and bone marrow. This is the first reported case of an MEM with initial bone marrow dissemination. The tumor consisted of a neuroblastoma component and a mesenchymal component with sarcomatous features. Diagnosis and therapy were complicated by the histological heterogeneity of the tumor, which also influenced the clinical appearance and course in this case. A literature search revealed 15 other evaluated cases that arose in soft tissue and had adequate clinicopathologic data. Complete surgical resection was the mainstay of treatment, and chemotherapy also appeared to be important. In all reported patients ( n = 3) with initial metastases or bone marrow dissemination, as in this case, no cure could be achieved. In patients with disseminated MEM, new therapeutic approaches such as high-dose chemotherapy followed by stem cell rescue should be considered, similar to the current strategy in patients with stage IV neuroblastoma or soft tissue sarcoma.