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Biomedical subjects

P H Lieberman

Publications and source records attributed to P H Lieberman.

At least 19 recordsLinked to original sources

Hepatobiliary neuroendocrine carcinoma in cats: a clinicopathologic, immunohistochemical, and ultrastructural study of 17 cases.

Hepatobiliary neuroendocrine carcinoma was diagnosed in 17 cats in a period of 10 years. Seven tumors were of intrahepatic origin, one of which was a composite containing components of epithelial and neuroendocrine carcinoma. Nine tumors were of extrahepatic origin, and one tumor was located in the gall-bladder. The cats were adult and geriatric, and the male : female ratio varied according to tumor group. Hepatomegaly, anorexia, weight loss, and vomiting were the most common clinical signs observed in the cats with hepatic neuroendocrine carcinoma. The cats with extrahepatic neuroendocrine carcinoma showed these signs plus icterus (5/9) and high concentrations of hepatic enzymes. Histologically, the hepatic neuroendocrine carcinomas had two patterns, one with acinar structures separated by vascular stroma lined by cuboidal or columnar cells and the other solid with groups of anaplastic cells separated by vascular stroma. The composite tumor consisted of both bile duct carcinoma and neuroendocrine carcinoma. The extrahepatic neuroendocrine carcinomas and the gallbladder neuroendocrine carcinoma were characterized by solid sheets or groups of round to oval cells with vascular or fibrovascular stroma. Immunohistochemical examination of 10 of the neuroendocrine carcinomas revealed that all 10 stained with neuron-specific enolase; one bile duct carcinoma and the gallbladder carcinoma stained with chromogranin; four of five bile duct carcinomas and the gall bladder carcinoma stained with synaptophysin; and one bile duct carcinoma stained with gastrin. One cat with hepatic carcinoma had duodenal ulcer; in this cat, ultrastructural studies showed neurosecretory granules leading to the diagnosis of Zollinger-Ellison syndrome. In four cats in which necropsy was permitted, carcinomatosis (4/4), lymph nodes (4/4), lungs (2/4), and intestines (1/4) were the metastatic sites. Fourteen of the 17 cats were euthanatized during or immediately after surgery.

Animals↗

Feline cystic thymoma: a clinicopathologic, immunohistologic, and electron microscopic study of 14 cases.

Cystic thymoma was diagnosed in 14 cats in a period of 6 years. The most common clinical sign was laboured breathing. The tumours were characterized by various-sized cystic spaces with central vessels. The epithelial cells varied from oval to spindle to polygonal cells enclosing cystic spaces or in pure epithelial cell components. The nuclei of the neoplastic cells had scattered chromatin and small nucleoli. The cytoplasm was pale eosinophilic. The concentration of mature lymphocytes varied from area to area with rare germinal centres. Immunohistochemically, the epithelial cells stained only with AE(1)/AE(3). The central vessels were positive for vimentin, smooth muscle actin, and factor VIII antigen. Electron microscopy revealed that the cyst walls were lined by epithelial cells that were joined by desmosomes, and the walls were well separated from the cystic spaces by a well-defined basement membrane. The neoplastic epithelial cells contained scattered tonofilaments. Three of the cats had metastasis to the lymph nodes and lungs. Two novel cases of ectopic cystic thymoma have also been described. Results of this study reveal that cystic thymoma is uncommon in cats, and that the histomorphologic, immunohistochemical, and electron microscopic features are similar to those of cystic thymoma in humans.

Animals↗

Langerhans cell (eosinophilic) granulomatosis. A clinicopathologic study encompassing 50 years.

We summarize our experience with 238 cases of Langerhans cell granulomatosis (LCG), 198 of whom were followed for a median period of 10.5 years. Our patients did well unless overtreated, and no deaths were attributed to the disorder itself. The disease may appear in unifocal or multifocal form, and treatment is based on this fact. Virtually all patients recovered completely except for occasional residual orthopedic problems or residual diabetes insipidus. Several of the patients underwent subsequent pregnancies without difficulty. The granulomas primarily occur in bone, but lung, skin, and lymph nodal involvement is not uncommon. Involvement of thyroid, thymus, and other sites is rare. The hallmark of the disease is the accumulation of Langerhans cells (LCs). We review the pathology of LCG by histology, electron microscopy, and immunolabeling. LCs originally were identified in squamous epithelium, but these cells are part of the widespread system of dendritic cells. The latter cells, which arise from CD34+ progenitors, are specialized and efficient antigen-presenting cells for T-cell-mediated immunity. In LCG, however, the major associated cells are not T cells, but mature eosinophils: hence the original name eosinophilic granuloma. Confusion about terminology has been based upon the scanty and rather crude pathology reports in the original literature. The term histiocytosis X was meant to cover a spectrum of three diseases--eosinophilic granuloma, Hand-Schüller-Christian disease (HSC), and Letterer-Siwe disease (LS)--but HSC and LS have no basis in pathology and hence the terms are meaningless. The term HSC has become a synonym for multifocal eosinophilic granuloma (LCG). The term LS has been used in reporting a number of benign, malignant, or unknown conditions. We prefer the term LCG to avoid confusion with the term histiocytosis X because there is evidence that the LC is not a member of the mononuclear phagocyte system and hence not a tissue macrophage, and because the use of the term "histiocyte" has become a convenience in much of the literature when reporting incompletely understood diseases.

Adolescent↗

Solid serous adenoma of the pancreas. The solid variant of serous cystadenoma?

Serous cystadenomas of the pancreas are uncommon benign neoplasms that occur most frequently in elderly females. Characteristically, the tumors have a spongy gross appearance and are composed of innumerable cysts lined by flat, cuboidal, and polygonal cells with clear to pale eosinophilic cytoplasm and round, hyperchromatic central nuclei. Macrocystic variants with an oligolocular gross appearance have also been described. In this report we describe a solid pancreatic neoplasm arising in a 70-year-old woman who remains well 5 years after a distal pancreatectomy. The well-circumscribed tumor measured 4.0 cm in maximal diameter and was formed by clear to pale polygonal to cuboidal cells arranged in nests, sheets, and trabeculae separated by thick fibrous bands. Although small acini with glandular spaces were present within the nests, cystic spaces were absent. Periodic acid-Schiff (PAS) and PAS-dismutase (PAS-D) stains revealed a large amount of cytoplasmic glycogen. The tumor cells were immunoreactive for CAM 5.2, epithelial membrane antigen, and neuron-specific enolase. The cytologic, histochemical, and immunohistochemical features of the tumor were indistinguishable from those of serous cystadenomas; therefore, we believe this solid serous adenoma represents a solid variant of serous cystadenoma. Recognition of this lesion is important because the vast majority of solid tumors in the pancreas are malignant. The differential diagnosis includes the rare primary clear-cell "sugar" tumor of the pancreas, clear cell carcinoma, clear cell islet cell tumor, and metastatic renal cell carcinoma.

Adenoma↗

Proteinaceous (angiocentric sclerosing) lymphadenopathy: a polyclonal systemic, nonamyloid deposition disorder.

Proteinaceous lymphadenopathy with hypergammaglobulinemia (PLWH) is an exceedingly rare disease of unknown etiology. Described primarily as a pathologic entity, relatively little is known about its clinical manifestations or its response to therapy. The disease is often referred to and treated as an unusual form of plasma cell dyscrasia or light chain deposition disease. We have recently encountered a young patient with PLWH who presented with generalized lymphadenopathy, marked liver function abnormalities, hypocomplementemia, cryoglobulinemia, decreased T4/T8 ratio, and ophthalmopathy. Contrary to the notion that PLWH is a clonal disorder, we found no evidence of clonality in this patient. The most characteristic finding in this and in another patient, previously seen at our institution, was marked angiocentric hyaline sclerosis of the small and mid-sized blood vessels of involved lymph nodes and organs. Based on these findings, we propose the term angiocentric sclerosing lymphadenopathy, which more accurately defines this clinicopathologic entity that appears to be distinct from light chain deposition disease and other plasma cell dyscrasias.

Adult↗

Extracranial primitive neuroectodermal tumors. The Memorial Sloan-Kettering Cancer Center experience.

The clinical data of 54 patients (57% males) with extracranial primitive neuroectodermal tumors (PNET) seen over a 20-year period at Memorial Sloan-Kettering Cancer Center were reviewed. The age at diagnosis ranged from 1 month to 81 years (median, 17 years). One PNET arose in a previously irradiated site. One patient had an unaffected identical twin. Primary sites were thoracopulmonary (n = 25), pelvis (n = 12), retroperitoneum or abdomen (n = 10), limbs (n = 5), neck (n = 1), and unknown (n = 1). At diagnosis, epidural extension was present in 13 patients with truncal primaries, and 11 patients had distant metastases. All of the latter died with disease. Progression-free survival (PFS) among the 43 patients with localized tumors (all greater than 5 cm) was 25% at 24 months. Two of 13 patients who relapsed after more than 12 months without therapy were long-term survivors. Patients with localized PNET who had resection of all gross disease within 3 months of diagnosis had a significantly longer PFS (P = 0.0003). Radiation therapy caused tumor shrinkage but was not curative of measurable disease. A dose-response effect was evident with the most commonly used drug, cyclophosphamide. Myeloablative regimens using melphalan (n = 8) or thiotepa (n = 1) with autologous bone marrow rescue were not clearly beneficial. The treatment results favor: (1) early surgical removal, (2) dose-intensive use of drugs active against PNET (especially cyclophosphamide), and (3) radiation therapy to ablate residual microscopic disease.

Adolescent↗

Gross, histologic, cytochemical, and immunocytochemical study of medullary thyroid carcinoma in sixteen dogs.

The gross, histomorphologic, cytochemical, and immunocytochemical findings in 16 dogs with medullary thyroid carcinoma were evaluated. Grossly, the neoplasms were encapsulated, firm, lobulated, and grey-white to tan. The typical histologic pattern was groups or sheets of round to polygonal cells with fibrovascular stroma, which was thickened and hyalinized in places. Variants of clear cell (two dogs), giant cell (one dog), and oxyphil cell (one dog) types were also seen. In all 16 dogs, Grimelius-stained sections of the neoplasms revealed intracytoplasmic silver granules; ten tumors contained amyloid and four contained mucin. Immunohistochemically, the neoplasms reacted to AE1/AE3 (n = 13), S-100 protein (n = 5), neuron specific enolase (n = 14), synaptophysin (n = 11), calcitonin (n = 16), somatostatin (n = 4), gastrin (n = 7), and serotonin (n = 6). Only one neoplasm was positive for vimentin. None of the neoplasms reacted to antibodies for neurofilaments, thyroglobulin, insulin, glucagon, or adrenocorticotrophic hormone. Eleven neoplasms contained multiple (two to four) peptides, in various combinations. It was concluded that in dogs, gross and histologic features can be used to distinguish medullary thyroid carcinoma from other thyroid malignancies. Cytochemical and immunocytochemical studies with neuron specific enolase, synaptophysin, and calcitonin can be used to establish the diagnosis of medullary thyroid carcinoma in dogs.

Animals↗

Lymphomas in dogs. A morphologic, immunologic, and clinical study.

One hundred seventy-six canine lymphomas were classified morphologically using four of the major human lymphoma classification schemes (Rappaport, Lukes-Collins, Kiel, and the Working Formulation). All 176 dogs received the same chemotherapeutic protocol. Sixty-two of these lymphomas had their immunophenotypes established by examination of cell surface markers by automated cytofluorography. Several different morphologic types of canine lymphoma were identified and these were comparable to morphologic categories in human classification schemes. Follicular and low grade lymphomas were rare. The two most common morphologic types were diffuse large cell (centroblastic) and immunoblastic. The Kiel classification appeared to be the most useful human scheme for classifying the canine lymphomas. Cytofluorographic analysis was generally straightforward, and 60 of the 62 lymphomas were placed into one of three immunophenotypic categories: 27 pan-T(LQ1)+SIg+, 21 pan-T(LQ1)-SIg+, and 12 pan-T(LQ1)+SIg-. Two of the lymphomas could not be characterized immunologically because a pre-existing or reactive non-neoplastic population of lymphocytes made interpretation of single cell suspension analysis difficult. The authors identified correlations between morphology and survival and disease-free remission; dogs with high-grade tumors generally survived the longest and had the longest remissions. No correlations were identified between high concentrations of serum lactate dehydrogenase, age, sex, or stage of disease, and morphology, immunophenotype, remission, or survival times. A significant correlation between clinical illness and survival time was documented. The median age of the dogs was nine years, no significant effect of sex on prevalence was observed, and some breeds were significantly overrepresented. Significant morphologic-immunophenotypic correlations included shorter remission and survival times for T-cell tumors than B-cell tumors, and a highly significant correlation between the pan-T(LQ1)+SIg-"T cell" phenotype and hypercalcemia.

Animals↗

Extra-adrenal pheochromocytoma (paraganglioma) in a cat.

Extra-adrenal pheochromocytoma (paraganglioma) arising from periadrenal tissue was diagnosed in an 18-year-old spayed domestic shorthair cat. The tumor was palpable on physical examination, but not apparent on plain radiographs. The cat developed temporary cardiac arrhythmia while the mass was being handled during excision, suggesting that the tumor was functional. The tumor was characterized histologically by nests and sheets of neoplastic cells separated by thin, vascular stroma. The cells had abundant eosinophilic granular cytoplasm and prominent nuclei. Diffuse, dark, intracytoplasmic granules were seen in sections stained with Grimelius stain. Ultrastructurally, the cells contained round and oblong, membrane-limited, dense core neurosecretory-type granules. Serotonin was detected in the cytoplasm of the neoplastic cells by use of immunocytochemical analysis.

Adrenal Gland Neoplasms↗

Immunohistochemical, molecular, and cytogenetic analysis of a consecutive series of 20 peripheral T-cell lymphomas and lymphomas of uncertain lineage, including 12 Ki-1 positive lymphomas.

Although several independent series of non-Hodgkin's lymphomas (NHLs) have been subjected to cytogenetic studies or analyses of lineages by assaying for clonal immunophenotypes and clonal rearrangements affecting immunoglobulin (IG) and T-cell receptor (TCR) genes, no published reports exist of series of non-B-cell NHLs on which cytogenetic, immunohistochemical, and IG and TCR gene rearrangement studies have been undertaken together. Among 343 NHLs ascertained prospectively between January 1984 and December 1988 at the Memorial Sloan-Kettering Cancer Center, 278 cases with clonal chromosome abnormalities were identified. Of the latter, 20 were non-B-cell NHLs, which in turn comprised 15 peripheral T-cell lymphomas (PTCLs) and 5 lymphomas of uncertain lineage (LULs). The LULs either were biogenotypic, had discordant immunophenotype and immunogenotype, or showed no evidence of B-cell, T-cell, or histiocytic derivation. Of the 15 PTCLs, eight expressed the Ki-1 antigen and four of these had translocations involving the band 5q35 [t(5q35)]. Of the five LULs, four expressed the Ki-1 antigen and one of these had a translocation involving band 5q35. Previous studies have associated t(5q35) with Ki-1 positive NHLs characterized histologically by a pleomorphic diffuse large cell morphology. In our series of 12 Ki-positive non-B-cell NHLs, five (42%) had a 5q35 translocation. They were histologically indistinguishable from the subset without the translocation. The frequent lineage uncertainty exhibited by Ki-1 positive NHLs of similar histology and cytogenetic abnormalities suggests their derivation from an early uncommitted lymphoid cells.

Antigens, Differentiation↗

Follicular neoplasms of the thyroid in men older than 50 years of age. A DNA flow cytometric study.

The clinical behavior of follicular neoplasms of the thyroid in elderly men can be difficult to predict on histologic grounds alone. To assess the usefulness of DNA flow cytometry in predicting the metastatic potential of these tumors, the authors studied 44 primary and metastatic follicular neoplasms of the thyroid by DNA flow cytometry of paraffin-embedded tissue. The neoplasms were obtained from 44 men ranging in age from 50 to 79 years (mean, 60). There were 29 follicular adenomas, 11 primary follicular carcinomas (neoplasms with capsular and/or vascular invasion), and 4 metastatic follicular carcinomas. Follow-up information was available on 40 of the 44 patients. The mean follow-up was 114 months. Twenty-five of the 29 follicular adenomas had a diploid DNA content, 2 (7%) were tetraploid, and the DNA histograms on 2 were not interpretable. All patients with follicular adenomas had no evidence of disease (NED) at last follow-up. Eight of the 11 primary follicular carcinomas were diploid. Six of these patients had NED, one died with carcinoma at 82 months, and no follow-up was available on one. Three (27%) of the primary follicular carcinomas were aneuploid or tetraploid. Two of these patients had NED, and the third died with carcinoma 84 months after diagnosis. Two of the four metastatic follicular carcinomas were diploid and two (50%) were aneuploid or tetraploid. One of the two patients with diploid metastatic follicular carcinomas died with carcinoma, as did one of the two patients with aneuploid metastatic follicular carcinomas. These results suggest the following: (1) follicular carcinomas are more likely to be aneuploid or tetraploid than are follicular adenomas; (2) follicular neoplasms without capsular or vascular invasion may include a small number of aneuploid or tetraploid tumors; and (3) DNA ploidy does not add to the prognostic value of histologic studies alone.

Adenocarcinoma↗

Alveolar soft-part sarcoma. A clinico-pathologic study of half a century.

In the period from 1923 to 1986 our pathologists examined pathologic material from 102 patients with alveolar soft-part sarcoma (ASPS). Followup clinical data is available for 91. Median followup is 7 years (range 1 month to 27 years). Local recurrence was only found if residual disease was left at the time of the original excision. Survival in those patients who presented without metastases was 77% at 2 years, 60% at 5 years, 38% at 10 years and 15% at 20 years (median 6 years). No survival advantage could be demonstrated for patients who received chemo and/or radiotherapy, although numbers are small and staging not uniform. An evaluation by electron microscopy and immunohistochemistry cannot confirm recent claims that ASPS is a muscle tumor. ASPS is an unusual neoplasm; the primary therapeutic option is aggressive surgical excision. Survival even with the development of metastases can be long.

Adolescent↗

Nonrandom chromosomal aberrations are associated with sites of tissue involvement in non-Hodgkin's lymphoma.

In an effort to assess the utility of pretreatment cytogenetics as indicators of sites of involvement by lymphoma, clinical and cytogenetic correlations were performed on 133 consecutive specimens derived from 130 patients with non-Hodgkin's lymphoma. Nonrandom chromosomal aberrations detected at the time of diagnosis were associated with sites of clinical involvement presenting initially or during the progression of the lymphoma. Statistically significant associations included translocation breaks involving the chromosomal region 1p32-36 and bone marrow involvement, chromosome 14 abnormalities including breaks at 14q22-24 and splenic involvement, chromosome 9 abnormalities and pulmonary involvement, and monosomy 11 and bone involvement. A significant correlation was also observed between breaks involving the region 6q22-24, detected during the course of disease, and bone marrow involvement by lymphoma. The relationship of the sites of nonrandom chromosomal breakage reported here to known cellular oncogenes and implications to concepts of tumor evolution and spread are discussed.

Bone Marrow↗

Cytogenetic and molecular genetic analysis of abnormal cells in Hodgkin's disease.

Eleven tumors from ten patients with Hodgkin's diseases (HD) were characterized by histologic, cytogenetic, immunophenotypic, and genotypic studies. Cell surface markers for lymphocyte antigens did not show clonal excess. Five tumors showed the presence of karyotypically abnormal cells, but no common abnormalities were found. The remaining six tumors showed normal karyotypes. Ten tumors were analyzed for gene rearrangements with probes for IgJH, IgCk. IgC lambda, and TCR-beta genes. The IgJH probe detected a minor clonal population (about 5%) in one tumor with abnormal karyotype; three tumors with abnormal karyotypes showed germline genotype. In contrast, four of the six tumors with normal karyotypes showed rearrangements in IgJH (one tumor) and in C-lambda (three tumors) genes. The pattern of gene rearrangement observed in these tumors did not obey the hierarchy described in B-cell differentiation. These results suggest that B-cell lineage cannot be attributed unequivocally to the clonal populations in HD.

Adolescent↗

Morphology of canine ovarian Sertoli-Leydig cell neoplasms. A report of 12 cases.

Of 71 dogs with primary ovarian neoplasms, 12 (17%) had Sertoli-Leydig cell tumors. Five dogs had Sertoli-Leydig cell tumors, four had pure Sertoli cell tumors, and three had Sertoli-Leydig cell tumors with a retiform pattern. Variously differentiated Sertoli cells were seen in the Sertoli-Leydig cell tumors, and one of these metastasized to the peritoneum. The pure Sertoli cell tumors were similar to these tumors in male dogs. The retiform pattern in the third group of tumors was characterized by tubuloalveolar structures resembling rete testes. Heterologous elements were seen in seven tumors (58%)--enteric glands in three Sertoli-Leydig cell tumors and one Sertoli-Leydig cell tumor with retiform pattern, and neuroendocrine carcinoma in one pure Sertoli cell tumor and two Sertoli-Leydig cell tumors with retiform pattern. The uterus was examined in seven dogs, and six (87%) had endometrial hyperplasia.

Animals↗