Alan D. Glick

Malignant lymphoma of peripheral T-lymphocyte origin: immunologic, pathologic, and clinical features in six patients.

In a continuing study of patients with lymphoproliferative diseases, six adult patients were encountered with a distinctive malignant lymphoma of peripheral T‐lymphocyte origin. Cell suspensions from lymph nodes of these patients contained a pleomorphic, cytologically atypical population of lymphocytes, of which an average 58% marked as T cells in the E‐rosette test. The average percent of surface immunoglobulin‐bearing B cells in these suspensions was 6%; they were of polyclonal distribution. Lymph node biopsies revealed a malignant lymphoma with certain characteristic features of the organization of the infiltrate, the morphology of the lymphoid cells, and the nature of non‐lymphoid cellular elements. The average age of the patients was 67 years; they presented with generalized lymphadenopathy, anorexia, and significant loss of weight. Four patients had lung and/or pleural involvement by lymphoma at presentation. The immunologic, pathologic, and clinical features of these patients serve to characterize this recently recognized malignant lymphoma further.

Aortic intimal sarcoma with embolic metastases.

A 46-year-old woman died from massive bowel infarction. At autopsy, a primary sarcoma was found growing along the intimal surface of the aorta at the level of the celiac axis. Tumor emboli were found in distal aortic branches and most abdominal organs. Immunoperoxidase for Factor VIII and electron microscopy (EM) did not support an endothelial origin. EM showed myofibroblastic differentiation. Review of the literature yields an array of diagnostic histologic terms for these tumors, hampering case comparison. The literature does suggest, however, that the clinical presentation of these rare neoplasms correlates nicely with the location and gross morphology of the lesion. We therefore propose a clinicopathologic classification, categorizing the lesions as intimal (obstructive and nonobstructive) and mural. The former are typically pleomorphic sarcomas and are probably of myofibroblastic origin, whereas the latter are usually leiomyosarcomas or fibrosarcomas that probably originate in the media or adventitia.

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

Abstract Hepatosplenic γδ 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 γδ 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. γδ T cell receptor (TCR) expression and clonal TCRδ gene rearrangements were documented in each case. Two different subsets of γδ TCL were identified based on δ chain variable region usage; two lymphomas were Vδ1+, whereas the third was negative for both Vδ1 and Vδ2. Cytogenetic analysis was performed on two lymphomas; isochromosome 7q and probable trisomy 8 was shown in one of the Vδ1+ lymphomas, whereas the Vδ1 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 × 2 FcR+ cells induced by anti-CD3 in a redirected cytolysis assay in one of the CD56+, Vδ1+ lymphomas, whereas IFNγ secretion was induced by anti-CD3 in the CD56-, Vδ1 negative lymphoma. These studies show that hepatosplenic γδ TCLs have CTL differentiation, retain functional activity in vitro, and are derived from at least two yS 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.

Rapidly Progressive Acute Renal Failure Due to Acyclovir: Case Report and Review of the Literature

Acyclovir nephrotoxicity has been described since the inception of the drugs use more than a decade ago. Acute renal failure mediated by this compound is characterized by abrupt elevations in serum creatinine and a gradual return to baseline renal function on discontinuation of the drug. Drug crystal formation in collecting tubules resulting in an intraparenchymal form of obstructive nephropathy has been suggested as the mechanism for acyclovir nephrotoxicity. The patient we present developed rapidly progressive acute renal failure with concomitant mental status changes in the setting of treatment with high-dose parenteral acyclovir. Acyclovir therapy was discontinued and an open renal biopsy was obtained to further evaluate our patients diminishing renal function. Pathologic examination of the biopsy specimen revealed loss of proximal tubule brush border and dilated proximal and distal tubules with flattening of lining cells and focal nuclear loss. No crystals were noted. These changes were consistent with acute tubular necrosis with regeneration. Over the next 4 days our patients renal and neurologic levels recovered to their prehospitalization statuses. It appears that our patient was affected by acyclovir-mediated nephrotoxicity that manifested on biopsy by acute tubular necrosis and the absence of crystalluria or crystal deposition. Intravenous acyclovir treatment can therefore produce rapidly progressive acute neurologic and renal toxicity that is usually reversible. The pathologic changes of acute tubular necrosis must now be included as part of the spectrum of renal damage associated with acyclovir therapy.

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 Bowmans 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.

Identification of Promonocytes and Monocytoid Precursors in Acute Leukaemia of Adults: Ultrastructural and Cytochemical Observations

Summary. Examination of 25 cases of adult non‐lymphoid acute leukaemia by electron microscopy and esterase cytochemistry revealed that most cases contained a majority of classifiable cells, however undifferentiated they may have appeared by routine light microscopy. The major proliferating cell in most cases (72%) was found to be a promonocyte or monocytoid precursor cell, characterized by extreme nuclear convolution, large cytoplasmic bundles of microfilaments, and numerous small electron‐dense lysosomal granules, which strongly stained for alpha‐naphthyl acetate esterase. Pure granulocytic cases, representing a minority (24%), were composed of blasts and typical promyelocytes and myelocytes, staining for Naphthol‐AS‐D chloroacetate esterase. Only one case was totally composed of undifferentiated, unclassifiable blasts. These results show that electron microscopy and cytochemistry increase the accuracy of classification of leukaemia and that the true incidence of monocytic leukaemia may be much higher than generally recognized.

Alveolar soft part sarcoma of the uterus

Two patients with alveolar soft part sarcoma of the uterus are described. One of the sarcomas was a submucosal nodule of the cervix, and the second was a minuscule, incidentally discovered lesion in the corpus. Both lesions contained periodic acid-Schiff-positive, diastase-resistant cytoplasmic granules, and characteristic membrane-bound crystalline inclusion bodies were demonstrated in the cervical lesion.

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. Ultra-structural 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 ana-plastic 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 ultra-structural 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.

Juxtaglomerular Cell Tumor of the Kidney

We describe an 11-year-old hypertensive girl who had a 5.0 cm. juxtaglomerular cell tumor. Of the 18 previously reported cases this appears to be the largest such tumor found. The benign nature of the tumor is emphasized, its clinical, radiological and microscopic appearance is illustrated, and appropriate treatment options are discussed.