Immunohistochemical expression of survivin in cutaneous sebaceous lesions.

BACKGROUND: Survivin is a member of the inhibitor of apoptosis family of proteins implicated in the inhibition of apoptosis and cell cycle control, both crucial in the progression to malignancy. Survivin overexpression has been demonstrated in numerous malignancies including cutaneous squamous cell carcinoma and melanoma. To date, there are no studies evaluating the expression of survivin in sebaceous neoplasms. METHODS: Immunohistochemical expression of survivin was evaluated in a total of 20 extraocular sebaceous neoplasms: sebaceous hyperplasia (SH, 8), sebaceous adenoma (SA, 8), and sebaceous carcinoma (SC, 4). All the results were independently evaluated by a single dermatopathologist. RESULTS: Nuclear expression of survivin was present in 1.4% of lesional SH cells, 8.2% of SA cells, and 12.5% of SC cells. A significant difference in survivin expression with the Student t test was noted between SH and SA (P=0.01), SA and SC (P=0.05), and SH and SC (P=0.001). CONCLUSIONS: There is a statistically significant difference in survivin expression among SH, SA, and SC. These findings demonstrate the potential diagnostic utility of survivin, further assisting in the microscopic differentiation of benign and malignant sebaceous neoplasms. However, larger studies are needed to determine the significance of survivin expression as it relates to recurrence, metastatic potential, and outcome.

Heterotopic ovarian splenoma: report of a first case.

We present a case of ovarian splenoma, a form of heterotopic splenic hamartoma consisting of red pulp tissue. The hamartoma was located in ovarian stroma in an otherwise normal ovary. The histology showed interanastomosing vascular channels of splenic sinusoidal red pulp lined by cells that were immunoreactive for antibodies to von Willebrand antigen and CD8, findings consistent with splenic lining cells. The sinuses were lined by cuboidal to flattened cells with ovoid and grooved bland-looking nuclei. Ultrastructurally, the tumor cells showed Weibel-Palade bodies and lysosomes. To our knowledge, this is the first case of splenic tissue arising in an ovary, and it underlines the trend noted in the literature that splenic hamartoma,although a rare entity, can arise in many retroperitoneal organs, including the ovary.

Allergic granulomatosis secondary to a limited form of Churg-Strauss syndrome.

Allergic granulomatosis is a disorder of obscure etiology characterized by infiltration of lymph nodes with histiocytic granulomas and eosinophils. In this report, we describe a case of allergic granulomatosis that is consistent with Churg-Strauss disease limited to lymph nodes. The histologic findings of this patient's lymph nodes demonstrated eosinophilic abscesses and ring-shaped necrotizing and nonnecrotizing granulomas surrounding hyperplastic germinal centers. We report herein a rare type of reactive lymphadenopathy and present its histologic, immunohistochemical, and flow cytometric findings, which may allow its distinction from other lymphadenopathies.

Effect of image compression on telepathology. A randomized clinical trial.

CONTEXT: For practitioners deploying store-and-forward telepathology systems, optimization methods such as image compression need to be studied. OBJECTIVE: To determine if Joint Photographic Expert Group (JPG or JPEG) compression, a glossy image compression algorithm, negatively affects the accuracy of diagnosis in telepathology. DESIGN: Double-blind, randomized, controlled trial. SETTING: University-based pathology departments. PARTICIPANTS: Resident and staff pathologists at the University of Illinois, Chicago, and University of Cincinnati, Cincinnati, Ohio. INTERVENTION: Compression of raw images using the JPEG algorithm. MAIN OUTCOME MEASURES: Image acceptability, accuracy of diagnosis, confidence level of pathologist, image quality. RESULTS: There was no statistically significant difference in the diagnostic accuracy between noncompressed (bit map) and compressed (JPG) images. There were also no differences in the acceptability, confidence level, and perception of image quality. Additionally, rater experience did not significantly correlate with degree of accuracy. CONCLUSIONS: For providers practicing telepathology, JPG image compression does not negatively affect the accuracy and confidence level of diagnosis. The acceptability and quality of images were also not affected.

Blastic transformation of splenic marginal zone B-cell lymphoma.

To our knowledge, blastic transformation of splenic marginal zone lymphoma, a recently characterized low-grade lymphoproliferative disorder, has not been reported previously. In this regard, we report the unique case of a 70-year-old woman whose untreated splenic marginal zone lymphoma underwent blastic transformation 3 years after diagnosis. Her hematologic medical history started in 1988 as thrombocytopenia refractory to steroids associated with atypical lymphoid infiltrate in the bone marrow. She underwent splenectomy in 1989, which revealed splenic marginal zone lymphoma. One year later, the patient developed lymphadenopathy noted in the chest, axillary, abdominal, and retroperitoneal lymph nodes. Because she was asymptomatic, treatment was limited to a conservative supportive regimen. The nodal lymphoma cells had features associated with marginal zone lymphoma and expressed B-cell monotypic kappa light chain. She was readmitted for the last time 2 years later with findings of 16% blasts in the peripheral blood and massive infiltration of the bone marrow by large blastoid cells. The blasts showed dispersed chromatin and prominent nucleoli, and possessed a moderate amount of clear cytoplasm. The blasts, like the previous nodal and splenic lymphomas, had a CD20-, CD19-, IgM-positive phenotype, but lacked reactivity for CD5, CD10, and CD23. The patient displayed clinical remission after treatment with vincristine and prednisone, but died of aspiration pneumonia 1 month later. These observations suggest that, similar to the other low-grade lymphoproliferative disorders, an untreated splenic marginal zone lymphoma may undergo high-grade blastic transformation.

Dermatomyositis as a presenting symptom of ovarian cancer.

BACKGROUND: Among gynecologic malignancies, the coexistence of ovarian cancer and dermatomyositis is most frequent. CASE: A 75-year-old woman presented with dermatomyositis, and a search for underlying malignancy found an otherwise asymptomatic ovarian carcinoma with para-aortic lymph node metastases. After resection and chemotherapy, the muscle weakness and skin lesions relating to dermatomyositis began to improve. CONCLUSION: Dermatomyositis can be the only presenting symptom of ovarian cancer, so an evaluation for suspected underlying malignancy should be done.

Immunophenotypic diagnosis of acute leukemia by using decision tree induction.

We describe a model for decision making for bone marrow immunophenotypic analysis of acute leukemia. In this study, we used decision tree induction as an information processing system for the analysis of flow cytometry immunophenotype results of bone marrow specimens obtained for the diagnosis of acute leukemia. By using decision tree analysis, we queried which antibodies and at what percentage cut-offs led to particular diagnoses. Flow cytometry results of up to 27 monoclonal antibodies from bone marrow specimens of 175 adult and pediatric cases were used: acute lymphoblastic leukemia (n = 80), myeloid leukemia (n = 44), mixed lineage (n = 16), and reactive marrow (n = 35). The percentage of positive cells was used as input data, and the diagnoses were used as output of the information processing system. Results of the decision tree showed an easy, accurate, and intuitive algorithm that can delineate a hierarchy of antibodies relevant to diagnosis. A correct discrimination of acute myeloid and lymphoid leukemia from benign bone marrow can be inferred by using the results of four to eight from a panel of up to 27 antibodies with an accuracy of 95%. Here, we describe a computer-aided model that uses decision tree induction applied to flow cytometry immunophenotype data. If generalizable, this technique may be an alternative approach to modeling complex information like that seen in hematopathology and may complement the immunologist's interpretation, along with cytochemistry and morphology results, in the diagnosis of acute leukemia.

Cytophagic histiocytic panniculitis--a syndrome associated with benign and malignant panniculitis: case comparison and review of the literature.

Many cases of hemophagocytic syndromes with cytophagic histiocytic panniculitis (CHP) are being classified and considered as a natural disease progression of subcutaneous panniculitic T-cell lymphoma (SPTL). Review of the literature on both CHP and SPTL discloses distinct patterns suggesting these disorders may not be equivalent, even though a terminal hemophagocytic syndrome may be associated with each. Some SPTL appear to have association with Epstein-Barr virus (EBV), show malignant histopathology in the skin, and may disseminate terminally, with a majority of cases showing a rapidly fatal progression. On the other hand, classic cases of CHP without proven lymphoma may not be associated with EBV, appear to be histologically benign, and have an indolent course unless terminal hemophagocytic syndrome develops. We compared and contrasted a case of CHP and a case of SPTL and reviewed the literature. Our observations suggest that the often fatal hemophagocytic syndrome may be associated with both benign and malignant subcutaneous panniculitis.

Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis.

We evaluated 48 archival cases of acute erythroleukemia and divided them into 3 groups: M6a, corresponding to the traditional French-American-British M6 category; M6b, which is pure erythroleukemia; and M6c, in which myeloblasts and pronormoblasts each account for more than 30% of cells by the French-American-British exclusion criteria. No significant differences were noted among the subtypes for ratio of males to females; age; or exposure to toxins, alcohol, or both. However, compared with the patients in the M6a group, patients in the M6b and M6c groups demonstrated a statistically significant increase in cytogenetic aberrations, proliferation markers (proliferating cell nuclear antigen and Ki67), and ringed (type III) sideroblasts. Marked survival differences were noted between the M6a (30.1 +/- 29.5 months) and M6b (3.15 +/- 4.2 months) groups, with patients in the M6c group demonstrating an intermediate prognosis (10.5 +/- 12.7 months). Chemotherapeutic regimens induced remission in all treated patients in the M6a and M6c groups but did not appear to affect the M6b group. However, the patients in the M6c group remained in remission for a significantly shorter period of time than did patients in the M6a group. Overall, survival appeared to depend on the ratio of pronormoblasts to myeloblasts at diagnosis and demonstrated a rapid decline with increasing pronormoblast and decreasing myeloblast counts. We must, therefore, devise chemotherapeutic regimens that target both blastic components of this disease.

Aggressive giant cell reparative granuloma of the metacarpal: a case report.

A 67-year-old woman presented with pain and swelling over her ring metacarpal. There was no history of antecedent blunt or penetrating injury. X-rays showed a progressively destructive lesion of the metacarpal shaft and base. Subsequent biopsy revealed a giant cell reparative granuloma. Because of here age and the presence of osteoarthritis and digital stiffness, a ray amputation was carried out. Follow-up examination 3 years later revealed no evidence of recurrence.

Hematologic malignancies developing in Syrian golden hamsters during induction of pancreatic carcinoma.

We report 30 hematologic malignancies arising in 25 of 236 Syrian golden hamsters (SGH) that received combinations of N-nitrobis(2-oxopropyl)amine (BOP) and Streptozotocin (STZ). Lesions developed with morphological similarity to human small lymphocytic (n = 7), diffuse mixed (n = 2), diffuse large cell lymphoma (n = 13), follicular lymphoma (n = 2), anaplastic large cell lymphoma (n = 3), hairy cell leukemia (n = 2), malignant histiocytosis (n = 1) and discordant lymphomas (n = 5). The types and distribution of these lesions are different from epizootic lymphomas in SGH. We also report a higher percentage (12 versus 4.6%) and the earlier appearance (< or = 40 versus 80-112 weeks) compared with aging-associated spontaneous SGH lymphoma. The features of these hematologic malignancies have not been previously reported in epizootic or aging-associated spontaneous lymphomas and therefore suggest a new class of hematologic lesions in SGH. Benign and atypical hyperplasia correlated with STZ administration (r = 0.97, P = 0.03). The malignant lesions correlated with areas of lymphoid hyperplasia (r = 0.78, P= 0.004). Only one of the 21 untreated SGH spontaneously developed a low grade lymphoma. The unusual types, distribution and occurrence of these lesions may suggest a role for these carcinogens in their induction.

Neural network analysis of flow cytometry immunophenotype data.

Acute leukemia is one of the leading malignancies in the United States with a mortality rate strongly influenced by the phenotype. This phenotype is based on detection of cell associated antigens normally expressed during leucopoietic differentiation. In this regard, leukemia classified as lymphoid or myeloid by phenotype is also classified as a candidate for the corresponding chemotherapy protocol. Additionally, the subtype of leukemia based on the degree of differentiation and cell maturity influence prognosis, response to treatment, and median survival times. In this paper, we analyze immunophenotype flow cytometry data toward categorization of leukemia into subcategories based on lineage and differentiation antigen expression. Twenty-eight inputs (derived from the mean fluorescence intensity of up to 27 antibodies, and an additional binary input denoting the past diagnosis of leukemia) are used as input to a neural classifier to categorize a total of 170 cases into the lineage and differentiation categories of leukemia. The neural classifier consisted of a feed forward network trained using back propagation. A complexity regulation term (weight decay) was used to improve the generalization performance of the neural classifier. A training error of 0.0% and a generalization error of 10.3% was obtained for categorization based on lineage, while a training error of 0.0% and a generalization error of 10.0% was obtained for categorization based on differentiation. These results indicate that objective classification of multifaceted phenotypes in leukemia can be achieved for analyzing multiparameter data in flow cytometry and further categorization into the prognostic subtypes.

CD34 immunostaining of bone marrow biopsy specimens is a reliable way to classify the phases of chronic myeloid leukemia.

Flow cytometry studies have shown that high expression of CD34 antigen in patients with chronic myeloid leukemia (CML) is indicative of accelerated or blastic phases. It has also been suggested that similar information can be obtained by CD34 immunostaining of bone marrow biopsy specimens. To test this hypothesis, the authors studied 59 conventionally fixed, paraffin-embedded bone marrow trephine biopsy specimens, representing the three phases of the disease (stable, accelerated, and blast crisis). Immunohistochemical staining for CD34 was performed using QBEnd10, a monoclonal antibody reactive in routine paraffin-embedded tissue. The differences in CD34 positivity among chronic, accelerated, and blastic phases of CML were highly significant (P = .0001). This study demonstrated that CD34 immunohistochemical staining of bone marrow biopsy specimens represents a reliable method for classifying patients with CML and may provide essential diagnostic and prognostic information when a marrow aspirate is unavailable.

The expression of H-like blood group glycolipids in small cell carcinoma of the lung.

Monoclonal antibody SM1 has been shown to be preferentially reactive with small cell carcinoma of the lung (SCCL) cell lines by fluorescent and radioimmunoassay membrane staining (1). Using solid phase indirect radioimmunoassay, the antigen is not detected in non-SCCL lung carcinomas histologically classified as squamous carcinoma, adenocarcinoma or large cell carcinoma, and other tumors, viz; pheochromocytoma, a mesoderm derived lymphoblastic leukemia cell line or in normal human brain, heart, liver, colon, endothelial tissues of the aorta and blood vessels, skin, omentum, muscle, lung parenchyma and is weakly reactive with bronchial mucosa, pancreas, and kidney. The membrane antigens detected by SM1 were isolated from small cell carcinoma of the lung (SCCL) cell line, SW2, using anion exchange chromatography and thin layer chromatography, and were further analysed by exoglycosidase and endoglycosidase treatments followed by chemical staining and immunostaining with SM1 and other antibodies. We show here that SM1 antibody reacts with a group of fucose-containing neutral glycolipids and gangliosides many of which are cross-reactive with antibodies to H antigens.

Primary squamous cell carcinoma originating in congenital cysts of the liver. Report of a case and review of the literature.

An 82-year-old woman developed a well-differentiated squamous cell carcinoma that apparently arose in two discrete congenital cysts of the liver. Both cysts were lined predominantly by stratified squamous epithelium with extensive areas of dysplasia and foci of transition to in situ carcinoma and overt exophytic and infiltrating squamous cell carcinoma. A third intrahepatic cyst was lined entirely by bile duct-type epithelium and contained no tumor. The liver was massively infiltrated by the carcinoma, and there were metastases to the lymph nodes, lung, and bone marrow. Since a search for an alternative primary tumor site was unrevealing, the authors interpret this as a unique case of primary squamous cell carcinoma originating in congenital cysts of the liver.