Hodgkindisease (HD) is characterized by a small numberofputativemalignant cells [HodgkinandReed-Sternberg (HRS) cells] among a background of lymphocytesandhistiocytes. The lineage ofHRS cells is still elusive anda clonal origin of these rare cells hasnot formally been demon-strated. Weisolated HRScells by micromanipulation fromhistologicalsectionsofthreecasesofHodgkinlymphoma(eachrepresenting a distinct subtype of the disease) and analyzedindividual cells for immunoglobulin variable (V) gene rear- rangements by PCR. In each of the three cases a singieheavy-chain V (VH) (and in one case, in addition, a K light-chain)generearrangement was amplifiedfromtheHRScells, identifying these cells as membersof a single done. A poten-tiallyfunctionalVHrearrangement was obtainedfrom acase ofnodular sclerosis HD. Somatic mutations and intraclonal di- versity in the VHgenesindicate a germinal center B-cell originof the HRScells in a case of lymphocyte-predominant HD,whereas ina caseof mixed-cellularity

Hodgkin disease: Hodgkin andReed-Sternberg cells picked from histological sections showclonal immunoglobulin gene rearrangements andappear tobederived fromB cells atvarious stages ofdevelopment

Hodgkin disease (HD) is characterized by a small number of putative malignant cells [Hodgkin and Reed-Sternberg (HRS) cells] among a background of lymphocytes and histiocytes. The lineage of HRS cells is still elusive and a clonal origin of these rare cells has not formally been demonstrated. We isolated HRS cells by micromanipulation from histological sections of three cases of Hodgkin lymphoma (each representing a distinct subtype of the disease) and analyzed individual cells for immunoglobulin variable (V) gene rearrangements by PCR. In each of the three cases a single heavy-chain V (VH) (and in one case, in addition, a kappa light-chain) gene rearrangement was amplified from the HRS cells, identifying these cells as members of a single clone. A potentially functional VH rearrangement was obtained from a case of nodular sclerosis HD. Somatic mutations and intraclonal diversity in the VH genes indicate a germinal center B-cell origin of the HRS cells in a case of lymphocyte-predominant HD, whereas in a case of mixed-cellularity HD the sequence analysis revealed only nonfunctional V gene rearrangements, suggesting a pre-B-cell origin. This indicates that HRS cells can originate from B-lineage cells at various stages of development.

https://www.pnas.org/content/pnas/91/23/10962.full.pdf

Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development.

Hodgkin and Reed-Sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription

Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists

Melanoma is the deadliest form of skin cancer. In the early stages, melanoma can be treated successfully with surgery alone and survival rates are high, but after metastasis survival rates drop sig...

https://www.tandfonline.com/doi/pdf/10.1080/15384047.2019.1640032

Current state of melanoma diagnosis and treatment.

We have assessed the degree of observer variation of both Breslow depth and Clark's level in a series of 50 thin malignant melanomas. Our findings are similar to those of previous international studies in the Breslow depth is the more reproducible measure. Significant intra- and inter-observer variation exists and in some cases it was up to +/- 0.86 mm. Even small differences will potentially affect patient management at our centre and this was analysed using kappa statistics. Good agreement was found between observers and this could be improved by comparing the mean of two or more measurements. This removes larger errors, but smaller observer errors and differences in subjective interpretation of the deepest malignant cell mean that agreement will never be more than 90 per cent. This is high compared with studies of observer variation in other pathological conditions, e.g., dysplasia of the cervix, but where surgical management is potentially disfiguring it is not high enough. We conclude that Breslow depth and Clark's level should not be the sole basis of wide excision protocols.

Observer variation in the measurement of Breslow depth and Clark's level in thin cutaneous malignant melanoma.

The lineage of Hodgkin and Reed-Sternberg cells is still unclear. Detection of both immunoglobulin light chains in Hodgkin and Reed-Sternberg cells by immunohistochemistry is a well-known phenomenon. However, up to now, in situ hybridization techniques have failed to demonstrate light chain messenger(m) RNA in Hodgkin and Reed-Sternberg cells. In this investigation, we have analysed 26 cases of Hodgkin's disease (nodular lymphocyte predominant Hodgkin's disease, mixed cellularity, and nodular sclerosis type) using digoxigenin-labelled oligonucleotide probes for kappa and lambda light chains by in situ hybridization. In nearly half of the cases of nodular lymphocyte predominant Hodgkin's disease and in one case of mixed cellularity type, mRNA for only one light chain could be clearly demonstrated in the lymphocytic and histiocytic cells, Hodgkin, and Reed-Sternberg cells. These results support the idea that at least some cases of Hodgkin's disease are B-cell neoplasms.

Peter S. Colloby

Papers

Observer variation in the measurement of Breslow depth and Clark's level in thin cutaneous malignant melanoma.

Demonstration of light chain mRNA in Hodgkin's disease