Through a series of biopsies, researchers documented first report case of an intermediate stage of lymphoma transformation

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n uncommon case of blood cancer non-Hodgkin lymphoma developing into classical Hodgkin lymphoma was recently described by American researchers in a case report published in AMOR journal.

“Through a series of biopsies, we report a unique case of diffuse large B-cell lymphoma (DLBCL) with stepwise development of classical Hodgkin lymphoma (cHL),” said pathologists Dr. Haipeng Shao and Pardis Vafaii from the Department of Hematopathology and Laboratory Medicine at H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. “To the best of our knowledge, this is the first report of an intermediate stage of transformation from DLBCL into cHL,” they added.

Lymphoma, or cancer in the infection-fighting lymphatic part of a human’s immune system, is categorized into two types: Hodgkin lymphoma and non-Hodgkin lymphoma – both with distinct behaviors and different treatment requirements.

Classical Hodgkin lymphoma – named after the 19th century British physician Thomas Hodgkin who first described the abnormalities in lymphatic system – is a less frequently diagnosed lymphoma subtype with tell-tale signs of abnormal lymphoid cells called ‘Reed­-Sternberg cells’ seen as giant purple nucleoli when examined under light microscopy.

90% of lymphomas, however, are of the non-Hodgkin lymphoma variety and do not exhibit the Reed­Sternberg cells. Of all the non-Hodgkin lymphomas, DLBCL is the most common type, which develops when white blood cells called lymphocytes (specifically the B-cell lymphocytes) starts dividing uncontrollably.

The distinction between DLBCL and cHL is clinically important as both respond differently to chemotherapeutic regimens, according to Shao and Vafaii. Moreover, “Classical Hodgkin lymphoma and non-Hodgkin lymphoma rarely develop in the same patient,” they explained. In their published case report, however, DLBCL and cHL was found to develop on the same anatomic sites, particularly on the skin of the patient, evidenced by the presence of cHL following the occurrence of DLBCL.

The patient was an elderly male with a history of stage IV DLBCL. Biopsies taken from the patient’s left arm and upper back revealed results consistent with DLBCL of the non-germinal center subtype. The patient then underwent chemotherapy, salvage therapy and an autologous bone marrow transplant.

Following the transplant, the patient’s biopsies started manifesting features of cHL, indicating a hybrid intermediate stage, according to the authors. “In the second biopsy…scattered Reed-Sternberg/Hodgkin-like cells were admixed with the DLBCL cells,” Shao and Vafaii wrote of the large atypical lymphoid cells which resemble Reed-Sternberg in cHL but do not develop into cHL.

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owever, despite these Reed-Sternberg/Hodgkin-like cells showing typical immunophenotype of cHL cells and were associated with limited inflammatory cells, “cHL diagnosis requires the presence of expansile lesion with a characteristic mixed inflammatory background associated with Reed-Sternberg/Hodgkin cells,” the authors explained, and “the Reed-Sternberg/Hodgkin-like cells neither seem to elicit a mixed inflammatory reaction nor form a discrete mass lesion within the large lymphoid cells,” rendering it difficult for the pathologists to diagnose cHL at this stage.

Three months later, however, an excisional biopsy performed on the patient’s lymph node no longer showed evidence of DLBCL but instead exhibited “many scattered clusters of Reed-Sternberg/Hodgkin cells with prominent cherry-red nucleoli in a background of small mature lymphocytes and granulocytes,” which are findings consistent with a cHL of the nodular sclerosis subtype, the authors reported.

The diagnosis of cHL established in the final lymph node biopsy therefore demonstrated that the Reed-Sternberg/Hodgkin-like cells found in the intermediate stage signaled the progression of DLBCL into cHL. “While Reed-Sternberg/Hodgkin-like cells are not uncommonly seen in a variety of non-Hodgkin lymphomas, the subsequent development of cHL in this patient indicated that the scattered Reed-Sternberg/Hodgkin cells among DLBCL cells truly represented a precursor of cHL,” the authors said, adding that the transformation would be possible for pathologists to diagnose, albeit very challenging.

Furthermore, “The identification of a hybrid intermediate stage suggested that [cHL and DLBCL] were clonally related,” the authors said, and recommended that the genetic changes in the cHL transformation could be further analyzed by examining individual Reed-Sternberg/Hodgkin-like cells in the precursor stage as well as cHL cells in later stages with subsequent molecular studies such as laser capture microdissection or next generation sequencing.

According to Shao and Vafaii, the case report was unique in which a stepwise transformation from DLBCL into cHL was demonstrated through a series of biopsies, which highlights the importance of repeated biopsies in diagnostically-challenging case. “Precursor or early lesions that could not be initially established diagnostically would eventually manifest themselves in later biopsies,” the authors concluded.