Malignant myopericytoma-like tumor in a Fischer rat.

Myopericytoma is a perivascular tumor that has been recently described in humans, but not in laboratory rodents. The authors encountered an intra-abdominal tumor resembling human malignant myopericytoma in a Fischer rat. Grossly, the tumor was found as two brown-colored masses located in the mesentery of rectum. Microscopically, the tumor was composed of oval to spindle-shaped cells, which were arranged in sheets around numerous thin-walled branching vessels and partly showed a concentric perivascular growth pattern. Mitoses were frequently seen, and the tumor cells showed a local invasion. Immunohistochemically, the tumor cells were strongly positive for alpha-smooth muscle actin and weakly positive for vimentin and desmin. Ultrastructurally, the tumor cells had dendritic processes, actin-like thin filaments with dense bodies, basement membranes, hemidesmosomes, and micropinocytotic vesicles. These findings suggest that the most appropriate term for diagnosis of the present case could be a malignant myopericytoma.

Intra-abdominal follicular dendritic cell sarcoma with marked pleomorphic features and aberrant expression of neuroendocrine markers: report of a case with immunohistochemical analysis.

Follicular dendritic cell sarcoma (FDCS) is a very rare malignant tumor arising most frequently in lymph nodes with only few reports of extranodal locations. We report the case of a 35-year-old man with a large retroperitoneal mass. Histologically the tumor was composed of highly pleomorphic cells exhibiting some uncommon features such as an epithelioid appearance, cystic spaces, and multinucleated cells with morphologic features of emperipolesis. Immunohistochemically the neoplastic cells were immunoreactive for CD21, CD23 and CD35. A previously unreported expression of neuroendocrine markers (Synaptophisyn and Neuron-Specific-Enolase) was present. Ultrastructurally no neuroendocrine secretory granules were detected. FDCS can mimic a wide variety of other malignant tumors, and a correct diagnosis requires exclusion of other neoplasms and immunohistochemical confirmation.

Clonal evolution in a human neuroblastoma.

Tumor samples, obtained from a single patient at two points in his illness, have enabled us to study clonal evolution in a neuroblastoma. Cells from the primary tumor demonstrated considerable heterogeneity in terms of chromosome number; cells from 4 subsequent metastases were all nearly diploid; and cells from a tumor produced in a mouse by the injection of cells from the primary tumor were hypotriploid in modal number. All of the tumor samples contained the same marker chromosome rearrangements, indicating their origin from a common precursor. Each of the cell lines analyzed (including those from the patient's metastases, those from the tumor in a mouse, and those from the primary tumor after 11 months in continuous culture) also contained different and distinguishing chromosome abnormalities. The differences in karyotype among these tumor samples and cell lines presumably reflect the different selection pressures at work in each instance.

Formation of undifferentiated mesenteric tumors in transgenic mice expressing human neurotropic polymavirus early protein.

The human polyomavirus, JCV, is the established etiologic agent of the human demyelinating disease, progressive multifocal leukoencephalopathy (PML) seen in immunosuppressed individuals. In PML patients, the viral early protein, which is produced exclusively in glial cells is responsible for initiation of the viral lytic cycle. The JCV early protein, T-antigen, has greater than 70% homology to the well characterized SV40 early protein which has established oncogenic properties. To investigate the role of JCV T-antigen in tumorigenesis, transgenic mice containing the viral early genome were produced. Of the four positive transgenic animals, one developed severe neurological abnormalities and succumbed to death at 3 weeks of age. Another animal died with no visible gross pathology and the cause of death was not determined. The remaining two founders developed massive, undifferentiated, solid mesenteric tumors with no obvious neurological symptoms. Results from histologic analysis demonstrated the presence of highly cellular, poorly differentiated neoplastic cells in the tumor tissue. Electron microscopic evaluation of the tumor revealed the presence of a small blue cell-like tumor of epithelial/neuroectodermal origin. Results from RNA analysis by non-quantitative and highly sensitive RT-PCR indicated the presence of the JCV early transcript in various tissues, including kidney, liver, spleen, heart, lung, and brain, as well as in the tumors. However, analysis of the viral early protein by Western blot and immunohistochemistry indicated high level production of JCV early protein in the tumor tissue, but not in any other tissues. These observations present the first evidence for the development of inheritable neuroectodermal tumors induced by the human polyomavirus, JCV, early protein in a whole animal system.

Demonstration of Epstein-Barr virus in immunoblastic sarcoma of B-cells arising in a child with primary immunodeficiency disease.

The subject of this investigation was an 11-month-old infant girl who presented with a pathological fracture of the right femur due to a metastasis from an abdominal immunoblastic sarcoma. Her past history included recurrent, intractable bacterial and fungal infections. Investigations of her immune status revealed low numbers of T-lymphocytes, a reversed T-helper (TH)/T-suppressor (TS) cell ratio, no response of her peripheral blood lymphocytes to pokeweed mitogen, phytohemagglutinin, concanavalin A, and Candida albicans, and an inability of her cells to react in a mixed lymphocyte culture. Serum levels of IgG, IgM, and IgA were all below normal. No thymic shadow was visible on the chest radiograph. There was no evidence of adenosine deaminase or nucleoside phosphorylase deficiencies. The tumor cells exhibited both surface IgM and IgG, and many of the cells contained large amounts of cytoplasmic IgM. Light chain specificity was restricted to lambda chain for both surface and cytoplasmic immunoglobulin. Ultrastructural study of the tumor cells revealed the presence of both intranuclear and cytoplasmic virions in roughly 1% of the tumor cells. These viral particles strongly resembled herpes viruses. DNA-hybridization studies on the neoplasm revealed the presence of 7-10 genome equivalents of Epstein-Barr virus-DNA per tumor cell.

Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres: a novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults.

The perivascular epithelioid cell family of tumors (PEComas), defined by their co-expression of melanocytic and muscle markers, includes angiomyolipoma, lymphangioleiomyoma, and clear cell "sugar" tumors of the lung, pancreas, and uterus. We present seven cases of a unique and previously unrecognized tumor of children and young adults, which represents a new addition to the PEComa group of tumors. Culled from three institutions over a 50-year period, all cases occurred in or immediately adjacent to the ligamentum teres and falciform ligament. Six patients were female and one male; their ages ranged from 3 to 21 years (median, 11 yrs). Tumor sizes ranged from 5 to 20 cm (median, 8 cm). All cases consisted of clear to faintly eosinophilic spindled cells arranged in fascicular and nested patterns. The cells had small but distinct nucleoli and low mitotic activity. Immunohistochemically, all cases were positive with antibodies to gp100 protein (HMB-45) and negative for S-100 protein. In three of the seven cases studied immunohistochemically, the tumors expressed smooth muscle actin, melan-A, microphthalmia transcription factor (MiTF), and myosin, but not desmin. No expression of the TSC2 gene product, tuberin, was seen in three cases. One case studied cytogenetically disclosed a t(3;10). Follow-up data, available in six of seven cases (median duration, 18 mos), showed five patients to be free of disease and one to have a radiographically presumed lung metastasis. We think these tumors comprise a new entity for which we propose the term "clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres." The differential diagnosis of these tumors includes clear cell sarcoma of tendons and aponeuroses, leiomyosarcoma, and angiomyolipoma.

Desmoplastic small round cell tumor: II: an ultrastructural and immunohistochemical study with emphasis on new immunohistochemical markers.

In order to investigate the histogenesis and facilitate the diagnosis of desmoplastic small round cell tumor (DSRCT), 39 cases were studied by immunohistochemical methods using a large battery of antibodies directed against a wide variety of epithelial, mesenchymal, and neural-associated proteins. Sixteen of these tumors were also studied by electron microscopy. Thirty-seven of 39 cases reacted for cytokeratin using a "cocktail" of 3 monoclonal antibodies (CAM 5.2/AE1/AE3), 39/39 for desmin, 24/25 for epithelial membrane antigen, 22/27 for vimentin, 18/25 for neuron-specific enolase, 10/15 for CD57 (Leu-7), 3/19 for synaptophysin, 1/22 for chromogranin, 3/19 for muscle-specific actin, 3/16 for alpha-smooth-muscle actin, 11/16 for CD15 (Leu-M1), 5/12 for CA-125, 6/17 for CD99, 9/10 for MOC-31, 2/6 for NB84, 5/7 for Ber-EP4, and 8/9 for the Wilms tumor (WT1) protein. No staining was obtained in any of the cases tested for cytokeratin 5/6 or 20, neurofilament proteins, glial fibrillary acidic protein, peripherin, CA19-9, thrombomodulin, alphafetoprotein, carcinoembryonic antigen, TAG-72 (B72.3), placental alkaline phosphatase, S-100 protein, HMB-45, myoglobin, or for the two myogenic regulatory proteins myogenin and MyoD1. A frequent ultrastructural finding was the presence of juxtanuclear aggregates of intermediate filaments, but microfilaments with densities or Z-band-like material suggestive of either smooth or skeletal muscle differentiation were not seen in any case. Dendritic-like processes containing microtubules and dense core granules were seen in four tumors and all of these tumors reacted for at least one of the neural markers investigated. Although ultrastructural and immunohistochemical studies confirmed previous observations that DSRCTs present epithelial, mesenchymal, and neural phenotypes, a great variation was found in the frequency of expression of the different markers used to demonstrate each line of cell differentiation. The absence of expression of cytokeratin 5/6 and thrombomodulin together with positive staining for CD15, MOC-31, and Ber-EP4 argues against the possible mesothelial origin that has been suggested for this tumor. Additionally since none of the tumors reacted for myogenin or MyoD1, desmin expression in DSRCT cannot be regarded as evidence of skeletal muscle differentiation. Although the histogenesis of DSRCT remains unknown, it is believed that this tumor originates from a progenitor cell with potential for multiphenotypic differentiation.

Intra-abdominal desmoplastic small round-cell tumor. Report of 19 cases of a distinctive type of high-grade polyphenotypic malignancy affecting young individuals.

Nineteen cases of a distinctive type of malignant small-cell tumor are presented. The main features of the entity are as follows: a predilection for adolescent males (mean age: 18.6 years); predominant or exclusive intra-abdominal location, with only inconstant and secondary organ involvement; nesting pattern of growth; focal rhabdoid features; intense desmoplastic reaction; immunohistochemical reactivity for epithelial [keratin, epithelial membrane antigen (EMA)], neural [neuron-specific enolase (NSE)], and muscle (desmin) markers; and highly aggressive behavior. It is proposed that this represents yet another member of the continuously enlarging and evolving family of small round (blue) cell tumors of infancy and childhood that features, more than any other member of this group, the capacity for simultaneous multidirectional phenotypical expression.

Hibernoma: a possible model of brown fat histogenesis.

Hibernomas are composed of cells remarkably similar to those observed in brown adipose tissue. A surgically resected hibernoma was observed to contain cells at all stages of maturation from immature, relatively lipid free cells to multiloculated and finally uniloculated adipocytes. The ultrastructural features of adipocytes contained in the hibernoma were compared to previously reported features of differentiating preadipocytes and lipid depleted mature adipocytes derived from human white adipose tissue. This comparison confirmed the existence of distinct mitochondrial and cytoplasmic membrane component differences at all developmental stages and suggests that brown and white adipose tissue are two unique histologic types.

Ovarian involvement by the intra-abdominal desmoplastic small round cell tumor with divergent differentiation: a report of three cases.

Three girls, one 14 and two 15 years of age, with the recently described neoplasm that has been designated "intra-abdominal desmoplastic small round cell tumor with divergent differentiation," and ovarian involvement at presentation are described. In two cases the ovarian tumor was initially thought to be the primary neoplasm. In all cases there was extensive extraovarian tumor at the time of presentation. The ovarian involvement was bilateral in two cases and unilateral in the third. Microscopic examination showed prominent nodular growth within the ovaries. The tumors were characterized predominantly by nests of small cells with hyperchromatic nuclei and scant cytoplasm separated by a prominent desmoplastic stroma. A few tubules containing mucinous secretion were present in one case. On immunohistochemical staining many of the tumor cells stained positively for cytokeratin, epithelial membrane antigen, desmin, and vimentin. Staining for neuron-specific enolase was present in two cases but was conspicuous in only one of them. Leu-7 was expressed by the tumor cells in two cases, and S-100 protein by one, giving further support to the possibility of neuroectodermal differentiation within some of these neoplasms. The two cases studied by electron microscopy both showed frequent intercellular junctions, basal lamina, cytoplasmic filaments, and sparse, small dense granules of either neuroendocrine or lysosomal type. Paranuclear aggregates of filaments were found in one case and cellular processes were prominent in the other case. The differential diagnosis in these cases was extensive and included a number of small cell tumors that may involve the ovary, either primarily or secondarily, in young females. The desmoplastic small round cell tumor should be considered in such cases when the appearances on routine examination are consistent with the diagnosis, and appropriate immunohistochemical stains should be performed to confirm the diagnosis.

An intra-abdominal small round cell neoplasm with features of primitive neuroectodermal and desmoplastic round cell tumor and a EWS/FLI-1 fusion transcript.

We report an intra-abdominal round cell tumor in a young man which exhibited the light and electron microscopic appearance of a peripheral primitive neuroectodermal tumor (PNET), in addition to the clinical and topographic characteristics, desmoplasia and a complex immunophenotypic profile of the intra-abdominal desmoplastic round cell tumor (DSRCT). Reverse transcription polymerase chain reaction revealed a EWS/FLI-1 fusion transcript as in PNET/Ewing's sarcoma, instead of the EWS/WT1 transcript of DSRCT. The tumor was also strongly positive for the mic2 protein. This is a unique case of a hybrid tumor arising in the peritoneal cavity of a young male. The existence of such a hybrid tumor in this location suggests that DSRCT and PNET may be related and possibly share a common histogenesis.

Solitary fibrous tumor of the abdominal wall: a report of two cases immunohistochemical, flow cytometric, and ultrastructural studies and literature review.

Solitary fibrous tumors have been described at many extrapleural sites in recent years. However, solitary fibrous tumors arising from somatic soft tissue occur only rarely and can pose problems in the differential diagnosis from other benign or malignant soft tissue tumors. The majority of solitary fibrous tumors occurring in the somatic soft tissue have been found in the extremities and limb girdles, and the head and neck regions. There have been only eight published cases located in the abdominal wall. We herein report two female patients who developed solitary fibrous tumors of the abdominal wall that were not in association with the underlying peritoneum. Histologically, both tumors were characterized by a variety of architectural patterns, alternating hypercellular and hypocellular areas, proliferation of plump spindle cells, thick keloid-like and/or amianthoid collagen bundles, and ectatic staghorn-like vessels. Both tumors showed a diffuse strong reaction for CD34 and vimentin as well as focal positivity for bcl-2 and smooth muscle actin. A striking predominance in females was found in a literature review of solitary fibrous tumors of the abdominal wall, contrasting with other somatic soft tissue sites which show an equal gender distribution. Interestingly, expression of estrogen but not progesterone receptor was observed in both tumors. Ultrastructurally, the tumor cells displayed features of fibroblasts with dilated branching rough endoplasmic reticulum (RER) and Golgi apparatus. Both tumors assayed by flow cytometry demonstrated a diploid DNA content with an S-phase fraction of 7.9% and 11.4%, respectively. At follow up, both patients were well without evidence of recurrence or metastasis after surgical excision.

Malignant fibrous histiocytoma: an ultrastructural study of six cases.

The ultrastructures of six malignant fibrous histiocytomas were studied. The lesions were composed of different proportions of fibroblastic- and histiocytic-appearing cells. Intermediate, undifferentiated, and foam cells also were present. Three of the lesions had some "fibroblasts" that had intracytoplasmic bundles of filaments with focal densities (myofibroblastic cells). Malignant fibrous histiocytoma is considered a sarcoma that has an undifferentiated mesenchymal cell origin, that differentiates along a broad fibroblastic and histiocytic (fibrohistiocytic) spectrum, and that usually has a predominant "fibroblastic" component.

Inflammatory malignant fibrous histiocytoma.

This report describes a 13-year-old girl with inflammatory malignant fibrous histiocytoma of the abdomen. Clinical, pathologic, and ultrastructural features of this subgroup of tumors are discussed. Differential diagnostic criteria are reviewed.

Trocar-site metastasis is not always due to laparoscopy.

The use of laparoscopic surgical techniques for the management of gynecologic malignancies has increased over the last years. Metastasis developing at the trocar insertion site is an emerging problem. We present the case of a 66-year-old woman with endometrial cancer who was diagnosed with an umbilical tumor after laparoscopically assisted vaginal hysterectomy (LAVH) and bilateral salpingoophorectomy. The interval between LAVH and diagnosis of the umbilical tumor was 13 months. The tumor was excised, and metastasis of endometrial cancer was histologically confirmed. Review of computer tomograms taken before LAVH showed a tumor in the umbilical area that had not been recognized before therapy. Therefore, tumor manifestation at the abdominal wall after laparoscopic surgery should not automatically be considered the result of iatrogenic spreading.

Electron microscopy of ultrasound-guided fine-needle biopsy specimens.

A prospective 3-year study was undertaken in order to assess the value of electron microscopy (EM) as a supplement to routine light microscopy (LM) in ultrasound-guided fine-needle biopsy of suspected abdominal and retroperitoneal tumours. Eight-six of the 899 ultrasound-guided fine-needle biopsies performed during this period were supplemented with EM using the following indications: metastatic lesions with unknown primary tumour, primary retroperitoneal tumours, tumours with atypical clinical histories and where the primary LM evaluation was unable to determine tumour cell type. Two methods of obtaining material for EM were tested, namely, fine-needle aspiration and fine-needle histological biopsy (Surecut). Both methods yielded suitable material for EM evaluation in approximately 80% of the 76 cases where tumour cells were identified by LM. However, it was technically easier to process material for EM when obtained by fine-needle histological biopsy. The results of the 62 cases where suitable material for EM was obtained were grouped according to the histopathological and clinical value of the diagnosis. In 23 cases (37%) EM was without additional diagnostic value. In 12 cases (19%), EM supplied a more precise histopathological diagnosis, but the diagnostic gain was without clinical significance. In 27 cases (44%) EM was of significant clinical value, as the diagnosis by itself was enough to change the investigative procedure and/or the treatment of the patient.

Intra-abdominal desmoplastic small-cell tumours with divergent differentiation. Report of two cases and review of the literature.

Two intraabdominal desmoplastic small cell tumours presenting in young adult males and involving the entire peritoneum, with no evident single primary site, have been studied. The histological pattern was suggestive of a metastatic small cell epithelial neoplasm, but immunohistochemical study revealed strong reactivity for cytokeratins, vimentin and desmin indicating synchronous epithelial and myogenous differentiation. In addition epithelial membrane antigen and neuron specific enolase were also positive. Electron microscopy showed fairly undifferentiated tumour cells with striking desmosome-like junctions, containing prominent paranuclear whorls of intermediate filaments, and a typical myofibroblastic stroma around neoplastic islands. Although the histogenesis of these recently described and rare tumours still remains uncertain, it seems that they constitute a reproducible entity which requires differential diagnosis from other small cell tumours of childhood and young adulthood.

Plexiform fibrohistiocytic tumor. Report of a case involving preoperative aspiration cytology and immunohistochemical and ultrastructural analysis of surgical specimens.

A typical case of plexiform fibrohistiocytic tumor (Enzinger and Zhang) occurring in the skin and subcutis of the abdominal wall in a 7-year-old girl is reported. Preoperative fine-needle aspiration cytology revealed a benign lesion with fibroblastic-histiocytic features which also contained bi- and multinucleated giant cells. The surgical specimen showed a tumor with multiple small nodules within fibrous septa; these nodules were composed of spindle cells and epithelioid cells and contained scattered multinucleated osteoclast-like cells. The tumor cells showed ultrastructural and immunohistochemical features of myofibroblasts and histiocyte-like cells. Thus, there was an abundance of lysosomes, prominent filopodia and bundles of thin cytofilaments along the cytoplasmic border, as well as immunoreactivity for alpha-smooth-muscle-specific actin, alpha-1-antitrypsin and alpha-1-antichymotrypsin. Ultrastructurally there were tumor cells exhibiting features of histiocytes which also contained bundles of actin of smooth muscle type. The presented case of plexiform fibrohistiocytic tumor appears to be composed of a rather peculiar cell form, somewhere between myofibroblasts and histiocytes.

Histiocytic lymphoma in a patient with Lennert's lymphoma. Report of a case with unusual cytoplasmic inclusions.

The transformation of Lennert's lymphoma into histiocytic lymphoma appears to be part of the natural history of the disorder rather than therapeutically induced. Unusual paranuclear nonmembrane-bound filamentous inclusions were found in many of the neoplastic cells in the histiocytic lymphoma. We report evidence for the immunoglobulin nature of this material, indicating a B cell origin of the neoplasm.

Annulate lamellae in human malignant tumors: report of three cases.

During the course of applying electron microscopy to diagnostic surgical pathological specimens, three malignant tumors (malignant melanoma, fibrous mesothelioma, lymphoblastic lymphoma) were found to contain annulate lamellae, distinctive intracytoplasmic organelles composed of membrane stacks interrupted by constrictions or pores. In one case both annuli and lamellae were present, a combination rarely described in human tissue and in animal models. In this material, the annuli of the annulate lamellae were structurally similar to nuclear pores. It is postulated that the abundant fibrils are probably related to the unusual configuration of the annulate lamellae. A morphologic relationship of the annulate lamellae to both the endoplasmic reticulum (cases 1 and 2) and the nuclear membrane (case 3) supports the theory that annulate lamellae may be related to both of these structures.