A 73-year-old man presented with a 6-month history of progressive papules and nodules involving the entire integument. The lesions initially appeared on the trunk and subsequently spread to the extremities and scalp. His medical history was notable for arterial hypertension and a severe COVID-19 infection complicated by pulmonary embolism 6 months earlier. The patient reported an unintentional weight loss of approximately 10 kg, which was attributed to the prior COVID-19 infection. No other B symptoms were present. On physical examination, multiple erythematous, subtly indurated plaques and nodules measuring 2–5 cm were observed, predominantly affecting the shoulder girdle (Figure 1). The lesions were non-scaly and non-ulcerated. Laboratory investigations revealed a normal differential blood count except for a known idiopathic thrombocytopenia with a platelet count of 60 G/L. A skin biopsy was performed (Figure 2). Primary cutaneous plasma cell myeloma with nodal involvement. Histopathological examination of the skin revealed a dense subepidermal infiltrate composed of slightly pleomorphic plasmacytoid cells (Figure 2). Immunohistochemical staining demonstrated monoclonal plasma cell proliferation with cytoplasmic kappa light chain restriction (Figure 3B). The tumour cells expressed EMA, CD79a and MUM1, while CD138, CD20, lambda light chains, CD56, and cyclin D1 were negative (Figure 3A,C). Given suspicion of a lymphoproliferative disorder, a PET-CT scan was performed. This revealed multiple metabolically active cutaneous and subcutaneous lesions involving the trunk and extremities, as well as numerous FDG-avid lymph nodes in the cervical, axillary, intrathoracic, retroperitoneal, and inguinal regions (Figure 4). Histological analysis of an excised inguinal lymph node demonstrated extensive infiltration by a plasma cell neoplasm of intermediate maturity with kappa light chain restriction. Evaluation for systemic multiple myeloma showed no evidence of bone marrow involvement. Serum protein electrophoresis and immunoglobulin levels were normal, and no Bence Jones proteinuria was detected. The CRAB criteria were not fulfilled, with haemoglobin at 12.9 g/dL, normal calcium and creatinine levels, and absence of osteolytic lesions. The patient was treated with a myeloma-based regimen consisting of daratumumab, bortezomib, lenalidomide, and dexamethasone (Dara-VRd), followed by autologous stem cell transplantation. Plasma cells neoplasms are characterised by clonal proliferation of malignant plasma cell clones producing monoclonal immunoglobulins 1. Multiple myeloma is the most common plasma cell malignancy and typically involves the bone marrow, leading to osteolytic lesions, anaemia, renal dysfunction, and hypercalcemia 2. Extramedullary disease occurs in approximately 4% of multiple myeloma cases, while cutaneous involvement is rare, affecting only 1%–2% of patients, usually as a late manifestation 2-5. In contrast, primary extramedullary plasma cell myeloma is defined by the absence of bone marrow involvement and systemic disease and most commonly presents as a solitary lesion in the upper respiratory tract, gastrointestinal tract, or lymphoreticular organs 1, 6. Primary cutaneous plasma cell myeloma is exceedingly rare and typically presents with solitary or multiple smooth, dome-shaped dermal or subcutaneous nodules on the face, trunk, or extremities 6. Diagnostic criteria include demonstration of monoclonal plasma cells by immunohistochemistry and exclusion of systemic multiple myeloma by imaging, bone marrow examination, and laboratory studies 6. Only few cases of multifocal cutaneous plasma cell myeloma have been reported in the literature 7. Moreover, simultaneous involvement of multiple lymph nodes without bone marrow disease represents an exceptional presentation, with fewer than 10 cases described 1. To our knowledge, concurrent involvement of skin and lymph nodes without systemic multiple myeloma has not been previously reported. While solitary plasmacytomas may be treated with local therapies such as surgical excision or radiotherapy, multifocal disease and nodal involvement pose a therapeutic challenge. Due to the unpredictable clinical course and risk of progression to multiple myeloma, a systemic myeloma-like treatment approach including chemotherapy and autologous stem cell transplantation is recommended 1. As the treatment responses can be rapid and perhaps curative, a risk of future progression to multiple myeloma remains and patients should be supervised frequently 1. Sarah Preis contributed to data collection, data preparation, and drafting of the manuscript. ASG contributed to histological data analysis and manuscript review. Mara Hubbuch contributed to manuscript review. Tilo Biedermann contributed to supervision. Oana-Diana Persa contributed to manuscript review and supervision. All authors have read and approved the final version of the manuscript and agree to be accountable for all aspects of the work. Open Access funding enabled and organized by Projekt DEAL. The authors received no specific funding for this work. All patients in this manuscript have given written informed consent for the use of their de-identified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical Approval: not applicable. SP, MH and ASG have no conflict of interest to declare. TB gave advice to or received an honorarium for talks or research grants from the following companies: ALK-Abelló, Janssen, Meda, Novartis, Phadia Thermo Fisher, Sanofi, and Celgene. Unrelated to this Study ODP declares honoria and travel support from Merck Sharp & Dohme, Kyowa Kirin, Pierre Fabre, Sanofi, Sun Pharma, Bristol Myers Squibb. Data are available on request. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Preis et al. (Mon,) studied this question.