Plasma cell neoplasms (PCN) include a spectrum of diseases that ranges from clinically indolent entities, such as monoclonal gammopathy of unknown significance (MGUS), to locally invasive neoplasms, including solitary plasmacytoma of bone, extraosseous plasmacytoma, such as primary cutaneous plasmacytoma, and finally to systemic neoplasms with aggressive clinical course such as multiple myeloma (MM) and plasma cell leukemia.

Skin involvement by PCN is rare, occurring in less than 2% of MM patients, and has been described only as single case reports and small case series.¹ IgA- and IgD-expressing tumors appear to have more frequent cutaneous involvement than other types of myeloma.² African-American males are more commonly affected.³ Cutaneous lesions may represent direct extension from underlying bone lesions or present as metastatic MM lesion. Primary cutaneous plasmacytomas that do not arise from underlying bone lesions are exceedingly rare.⁴

The majority of patients with primary cutaneous plasmacytomas are elderly or middle-aged with mean age, 59.5 years.⁵ The clinical manifestations include solitary or clustered erythematous papules, nodules, or subcutaneous plaques⁶ (Figs. 35-1A,B, 35-2, and 35-3). Some of them are not related to direct cutaneous infiltration by neoplastic plasma cells, but rather due to deposition of paraproteins they produce as in the case of amyloidosis and cryoglobulinemia.

In myeloma, skin lesions rarely develop early in the course of the disease or even during its first manifestation^7,8,9; most commonly cutaneous involvement appears late in the course. It is believed that cutaneous dissemination by MM occurs in the advanced stages, when the overall tumoral mass approximates 2 to 3 kg.¹⁰ The prognosis at this stage is dismal with average overall survival of less than 1 year.¹¹ Other cutaneous manifestations described in association with MM are listed in Table 35-1.¹²

Microscopic examination of skin lesions of MM usually demonstrates dermal-based nodular (Fig. 35-4A,B) and/or diffuse interstitial infiltrates of neoplastic plasma cells with sparing of the epidermis.⁶ The diffuse interstitial pattern is characterized by sheets and cords of neoplastic plasma cells infiltrating the dermis and subcutis. In some cases, the neoplastic cells can be easily identified as plasma cells showing intermediate-sized coarse, clumped chromatin, abundant cytoplasm, perinuclear Hoff, and variable nucleoli. The neoplastic tumor cells show variable maturation with occasional morphologic atypia including binucleation and multinucleation (Fig. 35-4C).¹ In some cases, given the degree of atypia, the recognition of a plasma cell dyscrasia can be very challenging (Fig. 35-4D). In such cases, the tumor cells are large with pleomorphic vesicular nuclei, prominent nucleoli, and granular eosinophilic cytoplasm. These are best characterized as plasmablasts. In those cases, mitotic activity is usually increased. A distinct grenz zone is commonly seen.¹ Intracytoplasmic inclusions (Russell bodies) and intranuclear inclusions (Dutcher bodies), although not usually prominent, may sometimes be present (Fig. 35-5A–D).^13,14