Lawrence M. Weiss

Detection of Epstein–Barr Viral Genomes in Reed–Sternberg Cells of Hodgkin's Disease

We used slot blot hybridization, Southern blot hybridization, and in situ hybridization to investigate the presence of Epstein-Barr virus (EBV) genomes in biopsy tissues from patients with Hodgkins disease. Slot blot hybridization performed on DNA of tissue specimens from 16 patients revealed that biopsy tissue from 3 (19 percent) contained EBV DNA. Southern blot hybridization with a DNA probe containing the 500-base-pair tandem repeated sequences located at the termini of the EBV genome confirmed the findings of the slot blot hybridization in the three positive tissue specimens and indicated the monoclonality of the EBV-infected cells in such tissues. In situ hybridization performed on the three positive specimens and on two from a previous study localized EBV nucleic acid to the Reed-Sternberg cells and variants in all specimens, with intense hybridization to Reed-Sternberg cells in two, less intense but consistent hybridization to Reed-Sternberg cells in two, and focal hybridization to Reed-Sternberg cells in one. We conclude that EBV genomes are present within Reed-Sternberg cells and variants in some patients with Hodgkins disease and that the infected cells are monoclonal.

Cytokeratin 7 and Cytokeratin 20 Expression in Epithelial Neoplasms: A Survey of 435 Cases

Cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) are low molecular weight cytokeratins. Their anatomic distribution is generally restricted to epithelia and their neoplasms. We surveyed 435 epithelial neoplasms from various organ systems by immunohistochemistry using CK 7 and CK 20 monoclonal antibodies. Expression of CK 7 was seen in the majority of cases of carcinoma, with the exception of those carcinomas arising from the colon, prostate, kidney, and thymus; carcinoid tumors of the lung and gastrointestinal tract origin; and Merkel cell tumor of the skin. The majority of cases of squamous cell carcinoma of various origins were negative for CK 7, except cervical squamous cell carcinoma, in which 87% of cases were positive. Approximately two thirds of cases of malignant mesothelioma were CK 7-positive. CK 20 positivity was seen in virtually all cases of colorectal carcinomas and Merkel cell tumors. CK 20-positive staining was also observed in cases of pancreatic carcinomas (62%), gastric carcinoma (50%), cholangiocarcinomas (43%), and transitional cell carcinomas (29%). The expression of CK 20 was virtually absent in carcinomas from other organ systems and in malignant mesothelioma. CK 7- and CK 20-negative epithelial neoplasms included adrenal cortical carcinoma, germ cell tumor, prostate carcinoma, renal cell carcinoma, and hepatocellular carcinoma.

Contemporary classification of histiocytic disorders

Pathologists and pediatric hematologist/ oncologists of the World Health Organizations Committee on Histiocytic/Reticulum Cell Proliferations and the Reclassification Working Group of the Histiocyte Society present a classification of the histiocytic disorders that primarily affect children. Nosology, based on the lineage of lesional cells and biological behavior, is related to the ontogeny of histiocytes (macrophages and dendritic cells of the immune system). Dendritic cell-related disorders of varied biological behavior are dominated by Langerhans cell histiocytosis, but separate secondary proliferations of dendritic cells must be differentiated. Juvenile xanthogranuloma represents a disorder of dermal dendrocytes, another dendritic cell of skin. The hemophagocytic syndromes are the most common of the macrophage-related disorders of varied biological behavior. Guidelines for distinguishing the exceedingly rare malignant diseases of histiocytes from large cell lymphomas through the use of a battery of special studies are provided.

Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors

A series of 43 adrenocortical tumors was analyzed using nine histologic features. Mitotic activity, especially with atypical forms, and venous invasion correlated best with metastasizing or recurring tumors; however, no single criterion was useful alone. The combination of the following nine criteria was most useful in distinguishing malignant from benign tumors: nuclear grade III or IV; mitotic rate greater than 5/50 high-power fields; atypical mitoses; clear cells comprising 25% or less of the tumor; a diffuse architecture; microscopic necrosis; and invasion of venous, sinusoidal, and capsular structures. None of the 24 tumors with two or less of these criteria metastasized or recurred, while all but one of the 19 tumors with four or more of these criteria either recurred or metastasized.

Keratin expression in human tissues and neoplasms

Keratin expression in human tissues and neoplasms

Molecular Analysis of the T(14;18) Chromosomal Translocation in Malignant Lymphomas

One of the most common karyotypic abnormalities is the t(14;18) translocation, which is found in many lymphomas that have a characteristic follicular morphology. Recent molecular studies have shown that this chromosomal translocation results in the juxtaposition of the candidate proto-oncogene bcl-2 (B-cell leukemia-lymphoma) on chromosome 18 with the immunoglobulin heavy-chain locus on chromosome 14. However, because performing accurate cytogenetic studies in solid hematolymphoid neoplasms is difficult, knowledge of the prevalence of the t(14;18) translocation and, by association, the extent of bcl-2 involvement in human lymphomas is limited. We used a number of chromosome-18 DNA probes to analyze various subtypes of Hodgkins and non-Hodgkins lymphomas and test for structural abnormalities near or within the bcl-2 gene. Molecular features of the t(14;18) translocation were found in virtually all follicular neoplasms and about 28 percent of diffuse large-cell lymphomas. No changes in bcl-2 were found in several other subtypes of Hodgkins and non-Hodgkins lymphomas, including those previously suggested to originate from follicular-center cells and those about which cytogenetic data have been difficult to obtain. Our findings suggest a close pathogenetic relation between bcl-2 and a large group of non-Hodgkins lymphomas, both with and without a follicular morphology. The methods employed in this study may be useful in improving the accuracy of diagnosis and subclassification of malignant lymphomas.

Pathologic features of prognostic significance in adrenocortical carcinoma

There are currently no well-established pathologic prognostic factors helpful in distinguishing low versus high grade adrenocortical carcinomas. The effect of 11 pathologic parameters on survival was investigated in 42 cases of adrenocortical carcinoma. Only one variable, mitotic rate, had a strong statistical association with patient outcome. The 21 patients with carcinomas with > 20 mitoses per 50 high power fields (hpf) had a median survival of 14 months, whereas the 21 patients with carcinomas with ≤ 20 mitoses had a median survival of 58 months (p < 0.02). The presence of atypical mitoses, capsular invasion, tumor weight > 250 g, and size > 10 cm each showed a marginal statistical association with poor survival (p < 0.06), whereas other features assessed, such as nuclear grade, presence of necrosis or of venous or sinusoidal invasion, character of the tumor cell cytoplasm, or architectural pattern, showed no statistical significance in predicting survival. It is proposed that adrenal cortical carcinomas with >20 mitoses be designated high grade, whereas tumors with ≤20 mitoses be designated low grade.

Tumours of histiocytes and accessory dendritic cells: An immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases

Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases

Description of an In Situ Hybridization Methodology for Detection of Epstein-Barr Virus RNA in Paraffin-Embedded Tissues, with a Survey of Normal and Neoplastic Tissues

The authors describe a highly sensitive and practical in situ hybridization method using an oligonucleotide probe for EBER1 RNA for the detection of Epstein-Barr virus (EBV) in formalin-fixed, paraffin-embedded tissue sections. Paraffin-embedded tissues from 793 cases of normal and neoplastic tissues were studied. Nuclear staining for EBV RNA was uniformly present in all or virtually all neoplastic cells in a variety of known EBV-positive tumors. We also demonstrate rare EBV-infected cells in normal lymphoid tissues. RNAase predigestion, competitive inhibition, and control probe studies confirmed the specificity of the staining. In addition, cross-reactivity of EBV RNA staining with other viruses was not present. Additionally, the distribution of EBV in a wide variety of other normal and neoplastic tissues is reported.

Clonal rearrangements of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy.

Histologic diagnosis of mycosis fungoides may be difficult, especially in lymph nodes that show changes frequently associated with chronic skin disease. As an alternative approach to diagnosis, we have analyzed the configuration of DNA for the beta T-cell receptor genes in biopsy tissues from 14 patients with mycosis fungoides. Clonal rearrangements of these genes were found in each specimen tht contained histologically unambiguous mycosis fungoides. Clonal rearrangements were also found in seven of nine lymph nodes removed from patients with mycosis fungoides and considered histologically to contain only benign lymphadenopathy. Matching rearrangements of beta T-cell receptor genes were detected in benign lymph nodes and histologically involved tissues when paired specimens were available from the same cases. Our findings provide molecular evidence for the clonal T-cell origin of mycosis fungoides and indicate the high incidence of extracutaneous disease in patients with palpable lymphadenopathy. In addition, this study demonstrates that the detection of rearranged T-cell receptor genes can be a sensitive and practical method for the diagnosis and characterization of T-cell neoplasms.