Cutaneous plasmacytosis is a rare entity consisting of a dermal infiltration of polyclonal plasma cells, with or without systemic manifestations including lymphadenopathy, fever, gammopathy, and in some cases infiltration of plasma cells into visceral organs. Given the frequency of extracutaneous manifestations of this disease, this entity is now preferentially referred to as cutaneous and systemic plasmacytosis (C/SP). In the past, cases without lymph node involvement have been termed “cutaneous plasmacytosis,” and the term “systemic plasmacytosis” has been applied only to patients who also have lymphadenopathy. This disease was first described in 1976 by Yashiro,¹ as a “kind of plasmacytosis” and later in 1980 by Kitamura et al.,² who defined “cutaneous plasmacytosis” as patients with skin lesions and polyclonal hypergammaglobulemia. In 1986, Wantanabe et al.³ classified a group of patients as having “systemic plasmacytosis,” noting characteristic skin findings, lymphadenopathy, and hypergammaglobulinemia. They postulated that the disease represented an overactive immune response to an unknown antigen. Given the rarity of this entity, and somewhat limited reports in the literature, much remains to be discovered regarding the pathogenesis, etiology, and management of this disorder.

C/SP is a rare entity, with fewer than 100 cases reported in the literature.⁴ Onset most commonly occurs in middle age, with a median age at diagnosis reported to be 49 years.⁵ This entity has also been rarely described in children, with cutaneous manifestations only, and low risk of systemic progression. This particular presentation has been referred to as benign primary cutaneous plasmacytosis.^6,7,8,9 One case in the literature reported this disease as being present since birth, identifying the possibility of the congenital nature of this entity.⁹ There is a slight male-to-female predominance, reported as 1.0:0.6 or 1.2:1.0.^10,11

C/SP most commonly affects individuals of Asian descent. By far, the most frequently reported are Japanese patients. There have also been rare cases in the literature of Chinese, Korean, and Vietnamese patients affected.^5,12,13,14 Even less common is this entity occurring in the Caucasian population. To date, around 10 patients of this particular subset have been documented.^{6,7,15,16,17,18,19,20,21}

The etiology of C/SP is unknown; however, many speculations have been made regarding the pathogenesis of this condition. Several studies have demonstrated an increase in interleukin-6 (IL-6) levels, implicating the cytokine as an important player in the pathogenesis of this disease.^5,22,23 As a key function of IL-6 is the differentiation of B cells to immunoglobulin-producing cells, namely plasma cells. One study showed that serum IL-6 levels parallel disease activity, and that effective treatment, in turn, also lowers the serum IL-6 levels.²³ The underlying reason and mechanism for the elevated IL-6 levels remain unclear. Another study postulated a similar pathogenesis as primary cutaneous marginal zone B-cell lymphoma, in which stimulation by an unknown antigen or infectious agent is responsible for the perpetuation of the disease.⁵ The authors of this study suggest that factors in the microenvironment of the skin or nearby lymph nodes stimulate IL-6 production, which in turn inhibits apoptosis of plasma cells and subsequently results in their proliferation.⁵ The exact stimulus for this proposed mechanism has yet to be determined. These noted elevations in IL-6, coupled with similarities in clinical presentation, have led to the speculation of C/SP being closely related to or on a similar spectrum as cutaneous plasmacytic Castleman disease.^5,24 Other studies have showed that human herpesvirus 8 (HHV-8) is absent in patients with C/SP, in contrast to most cases of multicentric Castleman disease, revealing a key difference in the pathogenesis of these disorders.^25,26 Elevated IgG4 levels in the serum and plasma cell infiltrate of cutaneous plasmacytosis have also been identified, bringing into question the possible relationship of this disease to a T_H2-mediated hypersensitivity reaction or IgG4-related sclerosing disease.²⁷ The striking geographical predominance has prompted the theory of an environmental or infectious cause; however, studies have failed to identify a causative organism.^12,28 Further studies are needed to elucidate the underlying pathogenesis of this condition.

The cutaneous manifestations of C/SP classically include red-to-brown-to-black macules, papules, and plaques (Figs. 50-1, 50-2 and 50-3). Lesions typically are evenly distributed, and located on the face, trunk, and extremities, with sparing of acral surfaces.⁴ It has been noted in some cases that the lesions follow skin lines, or a “Christmas Tree” pattern, similar to what is seen in pityriasis rosea.⁵ The lesions are often round or oval-shaped, and occasionally infiltrative. Lesions are typically asymptomatic, but may be pruritic in up to 40% of patients.^10,27

The most frequently reported extracutaneous manifestation is superficial lymphadenopathy, which is often asymptomatic, and has been reported as being present in up to 58% of patients.¹⁰ The lymphadenopathy has been noted in the cervical, axillary, and inguinal lymph nodes, and is typically multifocal and symmetric.⁵ Some studies have demonstrated infiltration of plasma cells into lymph nodes, in the absence of palpable lymphadenopathy on examination, citing this observation as a reason to evaluate for systemic involvement in all patients with this condition.¹¹ On laboratory examination, hypergammaglobulinemia is the most frequently reported abnormality and has been noted in up to 80% to 90% of cases.^5,10 This gammopathy is typically polyclonal; however, monoclonal gammopathy is rarely reported.^5,10,28 Most commonly involved are elevations of IgG, over 80% reported, followed by IgA and IgM. Elevated levels of IgE have also been demonstrated.⁵ Other commonly found laboratory abnormalities include elevated erythrocyte sedimentation rate (ESR) and anemia.^5,10 Bone marrow infiltration of plasma cells as well as infiltration of visceral organs, resulting in hepatosplenomegaly, can also occur.^5,10,11