Orbital leiomyosarcoma after retinoblastoma.

Patients with the inherited, bilateral form of retinoblastoma have an increased incidence of osteogenic sarcoma such that the mortality from the secondary tumor exceeds that of the initial bilateral retinoblastoma. We report a 29-year-old male survivor of bilateral retinoblastomas originally diagnosed at 8 months of age, whose treatment eventually included bilateral enucleation, bilateral orbital radiation, and systemic chemotherapy. At age 26, a tumor removed from his right maxillary sinus was diagnosed as fibroma. At age 29, he developed an inferior orbital mass that extended into the right maxillary sinus. A biopsy and comparison with the previous maxillary sinus mass revealed both lesions to be leiomyosarcoma. Both light and electron microscopy supported the diagnosis. The patient has survived treatment with orbital exenteration and maxillectomy combined with postoperative radiation to the right orbital-maxillary area. This appears to be the fourth case of leiomyosarcoma in the third decade of life in a male patient with a previously irradiated orbit after enucleation for bilateral retinoblastoma. Leiomyosarcoma appears to be another orbital tumor associated with bilateral retinoblastoma.

Microvillous lymphomas are B-cell neoplasms that frequently express CD56.

Microvillous lymphomas (MVLs) are rare, poorly defined, large transformed cell lymphomas characterized by a cohesive sinus growth pattern and ultrastructural cytoplasmic processes. Most MVLs express B-cell antigens and have been compared ultrastructurally to transformed follicular center cells and follicular dendritic cells. For additional definition of the immunophenotype of these unusual B-cell lymphomas, we evaluated eight cases of MVL for B-cell-associated antigens (CD21, CD35, CDw75, DBA.44, bcl-2) using paraffin immunoperoxidase. CD56, the neural cell adhesion molecule, was tested because of the unusual, cohesive, sinus pattern of tumor cell growth seen in MVL. Molecular analysis for immunoglobulin heavy chain and bcl-2 gene rearrangements was performed to confirm B-cell clonality and to evaluate cases for possible follicular origin. All of the cases were marked as B cells (CD20 positive), and the clonal nature confirmed by immunoperoxidase in five cases (63%) of eight and polymerase chain reaction for immunoglobulin heavy chain in seven cases (88%) of eight. CDw75 staining was present in six cases and CD74 in seven. DBA.44 and CD21 and CD35 were negative in all of the cases, and four cases (50%) of eight expressed CD56. bcl-2 protein expression was seen in seven of eight cases; bcl-2 gene rearrangement was present in one case (33%) of three studied. In conclusion, MVLs are B-cell lymphomas demonstrating clonal immunoglobulin heavy chain gene rearrangement. The neoplastic cells express CDw75 and bcl-2 protein. The presence of bcl-2 rearrangements in a limited number of cases implies that at least some MVLs have a follicular origin. Fifty percent of MVLs express CD56, suggesting a role for adhesion molecules in the distribution of this lymphoma.

Hepatosplenic gammadelta T-cell lymphoma: ultrastructural, immunophenotypic, and functional evidence for cytotoxic T lymphocyte differentiation.

Hepatosplenic gammadelta T cell lymphoma (TCL) is a rare, aggressive subset of peripheral TCL that presents with hepatosplenomegaly and cytopenias. Detailed clinicopathological, ultrastructural, and cytogenetic analyses of these lymphomas are limited; functional characteristics of these lymphomas are unknown. We have undertaken a clinicopathological, immunophenotypic, ultrastructural, cytogenetic, and functional analysis of three hepatosplenic gammadelta TCLs. All patients presented with massive hepatosplenomegaly and anemia, thrombocytopenia, or severe neutropenia; terminal blastlike transformation occurred in one patient. Combination chemotherapy had no response in two patients, but induced complete remission in one. gammadelta T cell receptor (TCR) expression and clonal TCRdelta gene rearrangements were documented in each case. Two different subsets of gammadelta TCL were identified based on delta chain variable region usage; two lymphomas were Vdelta1+, whereas the third was negative for both Vdelta1 and Vdelta2. Cytogenetic analysis was performed on two lymphomas; isochromosome 7q and probable trisomy 8 was shown in one of the Vdelta1+ lymphomas, whereas the Vdelta1 negative lymphoma had 14p+ with t(1;14)(q21;p13). NK cell-associated antigens (CD11c, CD16, or CD56) and cytotoxic T lymphocyte (CTL) effector proteins (perforin, granzyme B, TIA-1, and Fas ligand) were expressed by each lymphoma; dense core cytolytic granules were observed by electron microscopy in both lymphomas studied. Functional studies performed in two cases showed TCR-mediated cytolysis of P815 x 2 FcR+ cells induced by anti-CD3 in a redirected cytolysis assay in one of the CD56+, Vdelta1+ lymphomas, whereas IFNgamma secretion was induced by anti-CD3 in the CD56-, Vdelta1 negative lymphoma. These studies show that hepatosplenic gammadelta TCLs have CTL differentiation, retain functional activity in vitro, and are derived from at least two gammadelta T cell subsets.

Splenic marginal zone lymphoma. A distinct B-cell neoplasm.

The splenic marginal zone is a morphologically and perhaps immunologically distinct B-cell compartment. Lymphomas arising from cells of the splenic marginal zone are rare. Here we describe the morphologic, immunologic, and clinical features of 14 cases. Patient age ranged from 35 to 79 years (median, 68 years) with a male-to-female ratio of 1:1.8. The spleen was uniformly enlarged (median, 1,540 g; range, 388-3,845 g) in all patients, the neoplastic infiltrate had a nodular pattern in three cases, nodular and diffuse in seven cases, and diffuse in four cases. The neoplastic cells had small to medium-sized nuclei with round, oval, or slightly indented contours, small eosinophilic nucleoli, and a moderate amount of pale cytoplasm. Extrasplenic involvement was present in 12 patients. Lymph nodes often had a vaguely nodular pattern and preservation of sinuses; bone marrow was infiltrated focally (seven cases) or diffusely (one case). Five patients had hepatic involvement. Ultrastructurally, neoplastic cells differed from other small B cells and resembled normal marginal zone cells by having long, serpentine rough endoplasmic reticulum profiles. All lymphomas marked as B cells and light chain restriction was demonstrated in 12 cases. Bcl-2 protein expression was present in all cases. Most cases (70%) were negative for DBA.44 (CD72). Plasmacytic differentiation was present in three cases. In conclusion, splenic marginal zone lymphoma is a B-cell neoplasm with distinctive clinical, morphologic, immunologic, and ultrastructural characteristics.

Natural killer-like T-cell lymphomas: aggressive lymphomas of T-large granular lymphocytes.

Natural killer (NK)-like T cells are major histocompatibility complex-unrestricted cytotoxic T cells that are surface CD3-positive, express NK-cell antigens, and rearrange their T-cell receptor. Most neoplasms arising from this T-cell subpopulation have been a chronic lymphoproliferative disease referred to as T-large granular lymphocyte (LGL) leukemia. Only 10 NK-like T-cell lymphomas have been described in detail previously; this study presents the clinicopathologic features of six others and distinguishes these lymphomas from T-LGL leukemia. All patients presented with B-symptoms and often had marked hepatosplenomegaly without significant peripheral lymphadenopathy. Four of the six patients were immunosuppressed. All had CD3, CD8, CD56-positive tumors, presumably of hepatosplenic (n = 3), intestinal (n = 1), pulmonary (n = 1), or nodal (n = 1) origin. Three patients had lymphomatous bone marrow infiltrates, and four had peripheral blood involvement by neoplastic large lymphocytes, some of which had a blastic appearance or resembled virocytes. Azurophilic granules, ultrastructurally corresponding to cytoplasmic dense core and/or double density granules, were seen in all cases. T-cell clonality was shown in five tumors by Southern blot analysis, and three had abnormal karyotypes. Two untreated patients died 20 days after presentation, and three patients who received combination chemotherapy died within 5 months of presentation. One patient remains in complete remission 22 months after treatment. These findings suggest NK-like T-cell lymphomas are aggressive, are clinicopathologically distinct from T-LGL leukemia, and should be in the differential diagnosis of extranodal T-cell lymphoproliferations, including those in immunosuppressed patients. Furthermore, the LGL morphology, phenotype, and tissue distribution of some NK-like T-cell lymphomas suggest they arise from thymic-independent T cells of the hepatic sinusoids and intestinal mucosa.

Is focal segmental glomerulosclerosis really focal? Distribution of lesions in adults and children.

The distribution of lesions of glomerulosclerosis, whether focal or diffuse, has important implications for pathogenesis and potential therapeutic response. Determination of focal or diffuse nature of lesions from a single section, may, however, be misleading. We therefore evaluated the distribution of segmental glomerulosclerosis in patients with nephrotic syndrome and idiopathic focal segmental glomerulosclerosis (FSGS) by three-dimensional analysis. From our files, we identified all such biopsies with a diagnosis established by immunofluorescence, electron microscopy, and light microscopy that had > 10 glomeruli and serum creatine < 3.5 g/dl. Renal biopsies from 15 adults (9 women, 6 men, age 40.3 +/- 4.2 years and six children (2 girls, 4 boys, age 6.3 +/- 1.4 years) thus identified had sufficient serial sections for analysis. An average of 20.0 +/- 2.6 glomeruli in adults versus 25.2 +/- 3.9 in children were examined. Sclerosis assessed on a single section involved 31.5 +/- 6.8% of glomeruli in adults, contrasting only 11.7 +/- 5.7% in children (P < 0.05). Complete serial section analysis was possible in 14.1 +/- 1.6 and 10.7 +/- 1.6 glomeruli in adults and children, respectively. After this serial section analysis, the percent of glomeruli involved by sclerosis increased to 48.0 +/- 6.6% in adults and 23.2 +/- 7.4% in children (P < 0.025). The pattern remained focal in all but one case that had the highest serum creatinine. The greater increase in sclerosis after serial section analysis in children versus adults reflects the predominance of small peripheral, that is, more segmental, lesions in children than adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased interleukin-6 (IL-6) production in a young child with clinical and pathologic features of multicentric Castleman's disease.

A 21-month-old boy presented with a papular rash, lymphoadenopathy, and splenomegaly. He developed symmetric polyarthritis, fever, and progressive glomerulonephritis. Serologies for viral agents including HIV were negative. Antinuclear antibody was transiently positive, but no anti-DNA antibodies were present. CH50 and serum C3 values were low. Biopsies of skin, kidney, bone marrow, and lymph node were obtained. There was a perivascular and periadnexal lymphocytic infiltrate in the skin, with a normal epidermis. Renal biopsy showed proliferative mesangial glomerulonephritis. Bone marrow showed an increased number of plasma cells. Lymph node showed histologic changes described in multicentric Castleman's disease including marked follicular hyperplasia, vascular proliferation, and interfollicular expansion with numerous plasma cells. IL-6 mRNA was demonstrated in cells in the marginal zone and interfollicular regions of the node by in situ hybridization. Likewise, the serum IL-6 level was elevated during a clinical exacerbation of the patient's nephritis. These data suggest an underlying lymphoproliferative disorder, such as Castleman's disease, with overproduction of IL-6 resulting in systemic features of the disease, including glomerulonephritis.

Marrow mast cell hyperplasia in hairy cell leukemia.

Marrow mast cells, frequently elevated in chronic B-lymphoproliferative disorders, were counted per high magnification field (HMF) on toluidine blue stained marrow biopsies from 34 patients diagnosed with hairy cell leukemia (HCL); similar counts were performed on splenic sections from nine of these patients. Biopsies from 28 normal marrow transplant donors and 10 normal spleens served as controls. Mast cells were distributed irregularly throughout normal and HCL marrows, but tended to be more concentrated about the hairy cells in cases focally involved by HCL. HCL marrows averaged 12.7 mast cells/HMF compared to 1.1 for controls. Although most normal marrows (86%) averaged < 2 mast cells/HMF, 88% of HCL cases averaged > or = 2 mast cells/HMF. Splenic mast cells averaged < 1/HMF for both HCL and control cases. By electron microscopy, marrow mast cells in HCL demonstrated normal substructure with numerous granules. The cell surfaces of mast cells showed filopodia that often came in contact with those of hairy cells. These results indicate most HCL marrows, but not spleens, are associated with varying degrees of mast cell hyperplasia. Furthermore, this study suggests a biologic interaction between mast cells and hairy cells. The significance of marrow mast cell hyperplasia in HCL is unknown, but these mast cells may contribute to the increased reticulin fiber network observed in HCL marrows.

Melanocytoma of the ciliary body with scleral extension.

A 35-year-old woman had a circumscribed pigmented scleral lesion overlying a pigmented mass in the ciliary body and trabecular meshwork. Sclerectomy and iridocyclectomy were performed. Histologically, the lesion proved to be a melanocytoma. This represents to our knowledge the fourth reported case of scleral extension of a ciliary body melanocytoma.

Distant cutaneous metastasis of pleural malignant mesothelioma.

We report a facial tumor that was proven to be a metastatic mesothelioma. The diagnosis was not established pre-mortem. The patient died shortly after the facial biopsy, and an autopsy revealed a large pleural-based mass which had the gross appearance typical of a mesothelioma. Electron microscopic examination of tissue from the pleural tumor was diagnostic for mesothelioma. The patient had extensive visceral metastatic disease. Inclusion of this entity in the differential diagnosis of certain cutaneous tumors is important, in part because this lesion may be confused with angiosarcoma, particularly when it occurs in the skin of the face or head in older patients.

Mesangial deposition of type I collagen in human glomerulosclerosis.

The presence of type I collagen in both diffuse and nodular diabetic glomerular lesions has been examined using immunohistochemical and electron microscopic techniques. At the ultrastructural level, banded collagen fibrils were observed in the mesangium in all cases of nodular (Kimmelstiel-Wilson) sclerosis and in 60% of the diffuse sclerotic lesions. Antibodies against type I collagen were localized in the fibrotic interstitium and the mesangium in all cases examined. Staining with type I collagen antibodies occurred in glomeruli with intact Bowman's capsules, and was predominantly localized to areas immediately adjacent to mesangial cells. In cases of focal sclerosis of nondiabetic origin, banded collagen fibrils and staining with anti-type I collagen antibody were observed in all cases in which the segmental lesion was presented in the specimen. The pattern of antibody localization in both the diabetic lesions and focal sclerosis differed from that obtained using anti-type IV (basement membrane) collagen antibodies. These results demonstrate that type I collagen is among the extracellular matrix components that comprise the sclerotic glomerular lesions of both diabetic and nondiabetic origin. Furthermore, the spatial localization of this collagen type suggests mesangial cell origin.

Malignant lymphoma of the breast: a review of 13 cases.

Thirteen cases of primary malignant lymphoma of the breast are reported from a 15-year retrospective review of records. The ages ranged from 19 to 75 years. One patient had nodular sclerosing Hodgkin's disease and 12 had non-Hodgkin's lymphoma. Eleven patients were treated with local excision, followed by radiotherapy, chemotherapy, or both. One patient had mastectomy and chemotherapy, and one had local excision only. Four patients died 6 months to 7 years after initial diagnosis. One patient was alive and with disease 5 years later. The remainder were alive and free of disease 24 months to 9 years after presentation. Prognosis depended on the clinical stage and histologic grade of the lesion. Five-year survival was 72 per cent, which was slightly better than that observed in mammary carcinoma.

Plasmacytic differentiation in parafollicular (monocytoid) B-cell lymphoma. A study of 12 cases.

Parafollicular (or monocytoid) B-cell lymphoma (PBCL) is a recently described low grade lymphoma. The relationship of parafollicular B cells to other B lymphocytes is not known, but the authors observed plasmacytic differentiation in the initial case of PBCL. In this report 12 cases of PBCL were studied by light microscopy and immunophenotypic analysis, and plasmacytic differentiation was found in four cases. This plasmacytic differentiation and the anatomic relationship of the neoplastic cells to reactive follicular centers suggest a functional relationship between these cell types.

Primitive neuroepithelial tumors with vermiform processes (filiform neuroepithelial tumors). Immunocytochemical and ultrastructural study of 2 cases.

Two unique, poorly-differentiated neuroepithelial tumors are described, one in a 35-year-old woman with an anterior mediastinal tumor and one in a 71-year-old woman with a left femoral mass. Immunocytochemical stains demonstrated Neuron specific enolase in both tumors and Chromogranin in one. Electron microscopy showed the cells of both neoplasms to contain abundant, thick, vermiform, organelle-free processes, previously described solely in large cell lymphomas. Rare dense-core granules were present, and very few processes were suggestive of neurites. These observations enlarge the spectrum of poorly differentiated neuroepithelial tumors.

Adenovirus infection of the kidney: mass formation in a patient with Hodgkin's disease.

Adenovirus (AV) infection usually has a benign course in normal hosts; however, in immunocompromised patients, AV may cause pneumonia, cystitis, or disseminated disease with substantial morbidity and even mortality. Although pulmonic AV involvement is common, infection of the kidney is unusual. The histologic findings previously described include tubular necrosis with interstitial inflammation and glomerulonephritis. We report a case of an AV-induced unilateral mass lesion in the kidney of a patient with Hodgkin's disease (HD) following bone marrow transplantation.

Anaplastic large-cell Ki-1 malignant lymphomas. Recognition, biological and clinical implications.

Anaplastic large-cell Ki-1 lymphoma is defined by its characteristic histological appearance, reactivity with antibodies against CD30, and possibly by a chromosome marker t(2;5)(p23;q35). Because of its pleomorphic appearance, sinus distribution, and frequent reactivity with EMA, this lymphoma is often mistaken for other diseases such as metastatic carcinoma and malignant histiocytosis. The clinical features of this lymphoma are unusual and include a young median age and frequent extranodal disease with skin being a common site. Although remission is easily achieved, relapse is common and combination chemotherapy is suggested. The role of Ki-1 antigen in normal lymphocyte function, the cell of origin of anaplastic large-cell Ki-1 lymphoma, and its relationship to Hodgkin's disease are important questions that hopefully will be answered in the near future.

Comparison of anaplastic large cell Ki-1 lymphomas and microvillous lymphomas in their immunologic and ultrastructural features.

Anaplastic large cell Ki-1 malignant lymphomas (MLs) resemble microvillous lymphoma in having a pleomorphic infiltrate with a prominent sinus growth pattern. Ultrastructural features of anaplastic large cell Ki-1 MLs and their immunologic relationship to the microvillous MLs have not been thoroughly evaluated. We have studied 23 anaplastic large cell Ki-1 MLs immunologically as well as 14 cases ultrastructurally, and compared them with 7 cases of microvillous MLs. Anaplastic large cell Ki-1 MLs were predominantly T-cell in type (13 cases) with three cases marking as B; in seven cases the immunophenotype was not clearly defined. Six microvillous MLs expressed monotypic cytoplasmic or surface immunoglobin and the remaining case had a probable B-cell phenotype (LN-1+, UCHL1-). All microvillous MLs were Ki-1/Ber-H2 (CD30) negative. Epithelial membrane antigen (EMA) marked most anaplastic large cell Ki-1 MLs, except those of B-cell type, whereas all microvillous MLs were EMA negative. By electron microscopy, both lymphomas had features of transformed lymphocytes although anaplastic large cell Ki-1 MLs generally had more nuclear irregularity and variability from cell to cell. Numerous cytoplasmic processes were present in three anaplastic large cell MLs and in all microvillous MLs. The ultrastructural features of the cytoplasmic projections were not sufficiently distinctive to differentiate these two lymphomas. It is apparent that at least two forms of MLs may have a sinus growth pattern and that these MLs cannot be differentiated by morphology alone. Full characterization requires a battery of immunological markers and ultrastructural studies; even then there is overlap of these MLs. The majority of microvillous MLs, are Ki-1-, EMA-, and have a B-cell phenotype, but a small population (21% in this study) of Ki-1+ MLs have numerous cytoplasmic processes. The biological and clinical significance of cytoplasmic projections in these lymphomas are unknown.

Sterile corneal ulceration after cataract extraction in patients with collagen vascular disease.

We report the occurrence of sterile corneal ulceration in 11 eyes of eight patients with collagen vascular diseases and dry eyes after cataract extraction with intraocular lens implantation. Keratolysis occurred after both extracapsular and intracapsular cataract extraction and appeared unrelated to the type of intraocular lens. Despite aggressive lubrication and other medical treatment, including systemic immunosuppressive agents, penetrating keratoplasty was often required. Although all eyes were saved, visual outcome was usually poor. The histopathologic finding of polymorphonuclear leukocytes localized near the areas of corneal dissolution provides evidence for the role of polymorphonuclear leukocyte-derived collagenase as a contributing factor in the pathogenesis of sterile corneal ulceration in these patients.

Glomerular hypertrophy in minimal change disease predicts subsequent progression to focal glomerular sclerosis.

The study sought a diagnostic clue to identify the group of pediatric patients with apparent minimal change disease who subsequently develop focal glomerular sclerosis (FGS). Review of all renal biopsy material at our institutions identified 42 pediatric patients who met the standard criteria for minimal change disease (MCD) on initial biopsies. Of those, 10 deteriorated clinically and on rebiopsy showed focal glomerular sclerosis (FGS). The initial renal biopsies of these 10 patients were analyzed morphometrically to determine the mean glomerular tuft area (GA). The results were compared to those of the remaining 32 patients whose subsequent benign clinical course was consistent with MCD, and to randomly selected, age-matched autopsy controls without renal disease (CONT, N = 10). The mean age was comparable among the three groups studied. Separate groups of adult (N = 12) and pediatric (N = 18) patients with initial biopsies with FGS were also studied. The initial biopsy of pediatric patients who subsequently showed FGS (rebiopsy performed on average 3.3 years later) had an average GA of 13.5 x 10(-3) mm2, 76% larger than glomeruli from children with MCD (7.7 x 10(-3) mm2, P less than 0.0005) and 62% larger than CONT (8.4 x 10(-3) mm2, P less than 0.005). Patients with FGS on initial biopsy, whether adult or pediatric, also had significantly larger GA than the age-matched MCD or CONT groups. Evaluation of GA in all the 42 pediatric biopsies with initial MCD further showed that in 23 patients GA was equal to or smaller than the CONT average.(ABSTRACT TRUNCATED AT 250 WORDS)