Signet ring cell-like diffuse large B-cell lymphoma involving the breast: a case report | BMC Women’s Health

DLBCL is a high-grade lymphoma and the most common type of NHL [4]. DLBCL is highly aggressive, and patients usually present with rapidly expanding lymph nodes and systemic symptoms that require immediate treatment [4]. Although most patients present with swollen lymph nodes, approximately 40% of DLBCL cases arise from extranodal sites, including gastrointestinal tract, skin, soft tissues, mediastinum, bones, central nervous system (CNS), testes, and breast [5,6,7,8,9]. In addition, advanced DLBCL can involve extranodal tissues or organs, such as the bone marrow, pleura, peritoneum, liver, breast, and CNS, sometimes obscuring the primary site of origin [9, 10].

The spectrum of DLBCL is extensive and includes many morphological variants [10, 11]. Among these variants, DLBCL with signet ring cell characteristics is extremely rare. So far, only about seven cases of DLBCL with signet ring cells have been described in the literature; these originated from the lymph nodes, stomach, breast, orbit, and thigh [12,13,14,15,16,17]. Our case represents the first reported case of systemic DLBCL involving the breast.

In this case, the patient initially presented with a breast mass. Intraoperative frozen sections revealed aberrant cells arranged in a single row or scattered. Specifically, scattered signet ring-like cells were observed in the mesenchyme. This presented a diagnostic challenge. In fact, when such signet ring-like cells are observed, pathologists are more likely to consider metastatic adenocarcinoma of gastrointestinal origin or breast lobular carcinoma, causing misdiagnosis. The treatment options for these tumours are completely different. Therefore, it is important for pathologists to understand this rare morphological manifestation of DLBCL. When signet ring cell morphology appears, DLBCL should be considered in the differential diagnosis, and IHC studies using lymphoid markers, such as CD3 and CD20, should be performed first. Once the initial IHC suggests lymphoma, more extensive IHC and molecular testing should be performed to further classify the lymphoma. In addition, differentiating between primary and secondary DLBCL of the breast is important. The 2019 version of the World Health Organization diagnostic criteria for primary breast DLBCL includes being confined to one or both breasts, with or without involvement of regional lymph nodes [18]. In this case, PET-CT revealed the presence of metastases in multiple locations. Therefore, the final diagnosis was secondary DLBCL of the breast.

SRCL, most commonly described as a variant of follicular lymphoma, has rarely been described in DLBCL [1, 2]. DLBCL with signet ring cells involving the breast is rare, with only one such case described previously in the literature [13]. Kim et al., who first reported seven SRCL cases, divided SRCL into two types: one type had prominent, clear cytoplasmic vacuoles that contained IgG immunoglobulins, while the other had eosinophilic, hyaline, Russell body-type inclusions composed of IgM immunoglobulins [1]. It is currently believed that signet ring cells in lymphoma are divided into three subtypes: clear vacuole type, Russell body type, and hyaloplasmic deposit type, according to the morphologic and immunohistochemical characteristics [19]. The ultrastructural base of the clear vacuole type is an electron-lucent space limited by a smooth membrane, and deposition of IgG immunoglobulin exists at the periphery of the vacuoles. The Russell body-type is composed of dense granular materials and expanded pools of rough endoplasmic reticulum, related to aberrant secretion and accumulation of IgM. The hyaloplasmic deposit type shows cytoplasmic masses that contain immunoglobulins and correspond to non-membrane-bound hyaloplasmic accumulation of crystalline material. In the present case, immunofluorescence examination demonstrated that both IgM and IgG immunoglobulins were deposited in the cytoplasm of signet ring-like cells, which is inconsistent with previous cases reported in the literature. Our case for the first time demonstrated that signet ring like cells can have multiple types of immunoglobulin deposition at the same time, showing the characteristics of Russell body-type and clear vacuole type, which may represent a unique pathogenesis. To date, no study has reported that abnormal deposition of immunoglobulins has an impact on patient prognosis.

In conclusion, this is a unique case of signet ring cell-like DLBCL involving the breast. This morphological variant can be a serious pitfall for histological diagnosis, and immunohistochemical studies are very useful for differential diagnosis. However, it is important for pathologists to be aware that lymphoma can show a signet ring cell morphology and thus differentiate it from a metastatic signet ring carcinoma or breast lobular carcinoma. All of these can be confused with each other and have different behaviour and management protocols.

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