Telehematopathology in a clinical consultative practice.

We studied a series of 60 telepathology cases sent in consultation to the Department of Hematopathology from January 1, 1995, through July 31, 2000. Cases from the United States and the world representing academic, private, military, and federal sectors were reviewed. Ninety percent of patients were adults (54 of 60), and male patients outnumbered female patients 2 to 1. Ages were from 1 to 79 years (mean, 42 years). Forty-three cases were lymph nodes (72%), 14 were bone marrow or peripheral blood (23%), and 3 were from other sites (5%). Twenty-seven of the consultant diagnoses were benign (27 of 60). Twenty-nine were malignant (non-Hodgkin lymphoma, Hodgkin disease, and "other malignancy" groups), and 4 were nondiagnostic. Glass slide/paraffin tissue blocks were available in only 35 (58%) of 60 cases. The concordance rate for diagnostic telehematopathology cases with subsequent glass slide/paraffin block follow-up was 91% (29 of 32 cases). The discordance rate was 9% (3 of 32). This finding shows a high degree of diagnostic accuracy for consultative telehematopathology. Of 118 images analyzed, 58 were considered very good/good (49%), 32 were poor/very poor (27%), and 28 were fair (24%). Poor images had suboptimal resolution, color, or technical quality of transmission, and most poor images were low-power images. Additional case problems included insufficient immunoperoxidase stain availability, selection, and labeling; transmitted field selection; specimen preparation and staining; presence or absence of accompanying clinical data; and availability of ancillary studies such as flow cytometric, cytogenetic, and molecular data. From this analysis, the following recommendations are offered. To optimize telehematopathology consultation, include any additional information that have a significant influence on the final consultant diagnosis. Include any pertinent clinical information, laboratory data, special stains, immunoperoxidase stains, and molecular data. Select representative and diagnostically significant low-power and high-power fields for an accurate diagnosis. Label every immunostain or special stain submitted. Always send glass slides and tissue blocks when requested by the consultant. Optimize telemedicine microscopy and computer equipment with appropriate technical expertise, training, and support. In conclusion, the field of telepathology offers an exciting and potentially powerful solution to the problem of national and global subspecialty consultation. Hematopathology is potentially well suited to this technologically advanced marriage of computer and Internet technologies with modern microscopy, molecular diagnostics, immunophenotypic profiling, and the consultant pathologist.

Immunoperoxidase detection of CD10 in Precursor T-lymphoblastic lymphoma/leukemia: a clinicopathologic study of 24 cases.

CONTEXT: CD10 was originally reported in non-T-cell lymphoblastic lymphomas/leukemias. It has since been identified, however, in a minority of cases of T-lympho-blastic lymphoma/leukemia and other hematopoietic and nonhematopoietic entities. The usual method for the detection of CD10 previously required fresh tissue. A new antibody for CD10 (56C6) in paraffin embedded tissue sections, however, has recently become available. OBJECTIVE: To study the expression of CD10 in paraffin sections of T-lymphoblastic lymphoma/leukemia using monoclonal antibody 56C6. DESIGN: Twenty-four cases of T-lymphoblastic lymphoma/leukemia in various anatomic sites were studied. Immunohistochemical analysis with CD10 and a panel of other hematolymphoid antibodies was performed in all 24 cases. Gene rearrangement studies for the T-cell receptor by the polymerase chain reaction were performed in 18 of 24 cases. RESULTS: All cases were positive with at least 2 T-cell markers. In 15 (63%) of 24 cases CD10 was positive. T-cell receptor gene rearrangement was detected in 10 of 18 cases. CONCLUSIONS: Immunodetection of CD10 in T-lympho-blastic lymphoma/leukemia using monoclonal antibody 56C6 is common. This finding is useful in the evaluation of T-cell neoplasms.

Extramedullary manifestation of multiple myeloma (systemic plasmacytoma) that simulates hemangioma.

We describe 2 cases of a unique type of extramedullary manifestation of multiple myeloma (systemic plasmacytoma) that presented as subcutaneous nodules and mediastinal mass, respectively. Both lesions had a similar morphologic appearance, with dilated vascular-like lumina that was separated by thin fibrovascular septa, filled with erythrocytes, and lined by mature and immature plasma cells and plasmacytoid cells. The plasma and plasmacytoid lining cells showed kappa light chain restriction in both cases, consistent with a B-cell monoclonal process. The lining cells were also focally positive for epithelial membrane antigen but were negative for endothelial cell markers. Abundant delicate capillaries were seen in the septa that separated the vascular lumina, mimicking a vascular tumor. Furthermore, we believe that our cases are different from the previously described blood lakes in a plasmacytoma by the presence of well-formed fibrovascular septa that separated the vascular-like spaces. Neoangiogenesis propagated by myeloma cells may contribute to this unusual morphologic manifestation of extramedullary manifestation of multiple myeloma.

CD45 (leukocyte common antigen) immunoreactivity in metastatic undifferentiated and neuroendocrine carcinoma: a potential diagnostic pitfall.

Leukocyte common antigen (CD45/LCA) and keratin expression are generally mutually exclusive in diagnostic surgical pathology. CD45 reactivity is a reliable indicator of the hematolymphoid nature of a tumor, whereas keratin reactivity is typical of epithelial differentiation (carcinomas and some sarcomas). Some lymphomas, however, might lack detectable CD45 expression, whereas occasional ones might express keratins. CD45 immunoreactivity has been considered exquisitely specific for hematopoietic cells. We report three undifferentiated or neuroendocrine carcinomas that showed membrane-associated immunoreactivity for CD45 in addition to showing distinctive keratin cocktail (AE1/AE3) and epithelial membrane antigen reactivity (all cases); also, keratin 7 was demonstrated in one case and keratin 19 in another. Two cases were lymph node metastases of undifferentiated carcinomas, one of them from the lungs and the other of an unknown origin; the former case showed neuroendocrine features. The third case represented a pulmonary large-cell undifferentiated carcinoma. These cases were negative for lineage-specific leukocyte antigens and did not show clonal immunoglobulin heavy-chain gene rearrangements. Electron microscopic studies demonstrated desmosomes and keratin-like tonofilaments in all three cases, thus confirming the epithelial nature of these tumors. The exceptional membrane staining for CD45 seen in these undifferentiated carcinomas might be comparable to experimentally detected incorporation of leukocyte antigens into the cell membranes of nonleukocytic cells in a leukocyte-rich environment. This rare diagnostic pitfall should be considered in the diagnostic surgical pathology of undifferentiated tumors. It is best avoided by employing a panel of leukocyte and epithelial antigens and by use of electron microscopy, if possible.

Waldenström's macroglobulinemia: a clinicopathologic study of 22 cases.

BACKGROUND: Waldenström's macroglobulinemia (WM) is a rare immunoproliferative disorder, the clinical course of which varies. In related B-cell neoplasms, such as multiple myeloma and chronic lymphocytic leukemia, the histologic features of bone marrow are considered to be of prognostic relevance. METHODS: To assess the prognostic features of WM, the authors reviewed the clinical and pathologic features of 22 patients. Bone marrow aspirates and core biopsies were available for each case. Immunostains for a panel of hematopoietic markers as well as p53 and proliferating cell nuclear antigen (PCNA) were performed. RESULTS: There were 14 males and 8 females, with a mean age of 60 years. At presentation, two histologic subtypes, lymphoplasmacytoid (73%) and lymphoplasmacytic (27%), were observed. Four patterns of bone marrow infiltration were delineated: diffuse (45%), nodular-interstitial (22%), mixed paratrabecular-nodular (20%), and paratrabecular (13%). In 11 patients, the infiltrate occupied greater than 70% of the bone marrow; in 8 patients, 30-70%; and in 3 patients, less than 30%. PCNA reactivity was observed in 58% of cases and p53 reactivity in 21%. Ten patients died of disease with an average survival of 84 months. The remaining 12 patients were alive with disease at last follow-up. The pretreatment parameters that were correlated with shorter survival were hemoglobin, white blood cell count, platelet count, splenomegaly, lymphadenopathy, and serum immunoglobulin M level. CONCLUSIONS: The findings of this study suggest that some pretreatment parameters, such as cytopenia, serum immunoglobulin M level, splenomegaly, and lymphadenopathy, correlate with poor prognosis for patients with WM. In contrast, histologic features and expression of p53 and PCNA did not correlate significantly with survival.

Childhood Hodgkin's disease in the United States: an analysis of histologic subtypes and association with Epstein-Barr virus.

Hodgkin's disease (HD) typically has a bimodal age distribution and is less common than non-Hodgkin's lymphoma in the pediatric age group, especially in very young children. Recent reports described a high prevalence of Epstein-Barr virus (EBV) in HD from developing countries in both adult and pediatric populations. In this series, we studied with immunohistochemical analysis 44 cases of pediatric HD from the United States to investigate the association with EBV in developed countries and to determine which subtypes occur in this group. The 44 cases (40 boys, 4 girls; male-to-female ratio, 10:1) were categorized as nodular lymphocyte predominance in 16 (36.4%) of 44; nodular sclerosis in 13 (29.5%); and mixed cellularity in 4 (9.1%). Eleven of the cases were difficult to subclassify by the usual morphologic and immunophenotypic criteria. Of these, eight (18.1%) were designated interfollicular HD, and three were classified as HD "not otherwise specified." EBV LMP was positive in 38.6% of cases: 5 (38.5%) of the 13 with nodular sclerosis; 3 (75%) of the 4 with mixed cellularity; 1 (6.0%) of the 16 with nodular lymphocyte predominance; 7 (87.5%) of the 8 with interfollicular HD; and 1 (33.3%) of the 3 with HD "not otherwise specified." There was a strong association between the age of the patient and EBV expression. In children 4 years or younger, all of the 3 cases were LMP positive; in the 5- to 9-year-old age group, 8 (61.5%) of 13 were LMP positive; and in the 10- to 15-year-old group, only 21.4% were positive. Our results confirm the male predominance in pediatric HD and show an association with EBV, especially in the youngest patients and with the mixed cellularity and interfollicular subtypes. Most, but not all, cases of pediatric HD can be subclassified by traditional criteria.

Evaluation of albumin-globulin ratio to confirm the clinical stages of sarcoidosis.

The serum albumin-globulin ratio (A/G) has been evaluated and correlated to confirm the clinical stages of sarcoidosis in clinically diagnosed cases. In comparing each clinical stage of sarcoidosis, using Student's t test (P = .05), a significant difference was observed. Overall, men maintained a higher A/G ratio than women in all of the clinical stages. The authors conclude that the serum A/G ratio, which can be computed from serum analyses of albumin and globulins by a suitable method, can be an additional and reliable index requiring no extra serum sample or cost per test to confirm clinical stages of sarcoidosis. This measurement can easily be used in monitoring the progression of disease or efficacy of the therapy.