"A unique case of Hodgkin lymphoma with signet ring cells"

Authors of the case:
Resident: Vygantė Maskoliūnaitė; Consultant: Ugnius Mickys MD

A 57-year-old male presented with complaints of an episodic fever and night sweats lasting for about three months. Two months after the beginning of symptoms, he noted an enlarged inguinal lymph node. A computer tomography scan showed generalized lymphadenopathy and multiple nodules in spleen. A biopsy of the inguinal lymph node was performed, and Hodgkin lymphoma was suspected. The patient was admitted to the hematology department for further investigation and the material from biopsy was sent to our center for consultation.
Clinically,an enlarged 5-cm-diameter left inguinal lymph node was palpated. PET-CT scan showedmetabolically active cervical, mediastinal, abdominopelvic lymphadenopathy with splenic nodules.

A large lymph node had a thickened capsule and an effaced architecture with thick fibrous septations and partial nodal formations. Numerous atypical mononuclear giant cells with high N/C and prominent nucleoli were observed scattered or in clusters. Also, rare binucleated giant (Reed-Sternberg) and immunoblast-like cells were seen. Rich macrophages and fibroblast, also, less common lymphocytes and eosinophils formed the background.  To our surprise, a part of the cell population had signet ring cell appearance with a large, clear vacuole in cytoplasm and an eccentric, a bit hooked nucleus with prominent nucleoli.

T lymphocytes formed predominant part of infiltrate in the background, especially CD4-positive lymphocytes. ALK/ EBV LMP1/ EBER reations were negative. Overall, Ki67 proliferative activity reached 60%.
Giant and signet ring cells were strongly positive for CD30, CD15 and Fascin. 80% of these cells were weakly positive for B markers (PAX5, CD79a). Giant cells expressed MUM1, Bcl2, Vimentin and 20% of cells were weakly positive for CyclinD1. BOB1/Oct2, CD10, T markers (CD3/CD7), Bcl6, LCA, cMYC were negative. Signet ring cells did not express PanCytokeratins or CD68 and were considered as feature of lymphoma.

A final diagnosis of classical Hodgkin lymphoma, nodular sclerosis (grade 2, WHO) with unusual signet ring cells was made, considering full cHL immunohistochemical panel. It was noted, that differential diagnosis included grey zone lymphoma due partial DLCBL histological appearance in surrounding infiltrate.
After two cycles of chemotherapy, control PET-CT scan showed partial metabolic response without progression of disease. Minimal residual activity was observed in paraaortic and inguinal lymph nodes.

Signet-ring cell lymphoma (SRCL) is considered as a rare morphologic variant of non-Hodgkin lymphoma. Less than 100 cases of SRCL was published in English literature to date. Mostly, it was described as B cell lymphomas, including plasmacytoma/multiple myeloma. T cell lymphomas were less common. Non SRCL cases were diagnosed with Hodgkin lymphoma. It was noted, that signet ring appearance can be caused by cytoplasmic accumulation of immunoglobulin or vacuoles derived from multivesicular bodies.  Presumably, the presence of signet ring cells does not appear to affect the prognosis of the underlying subtype of lymphoma. However, the main reason to recognize this rare variant is misdiagnosis of metastatic signet ring cell carcinoma, which has poor prognosis in most cases.

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