Plasmacytic cutaneous pathology: A review
We review the spectrum of cutaneous disorders associated with inflammatory and neoplastic plasmacytic pathology. Because plasma cells are derived from B‐lymphocytes our overview includes discussion of certain lymphoplasmacytic proliferations. It is structured along histopathological lines, addressing conditions characterized by (a) cutaneous plasma cell infiltrates, (b) deposits of plasma cell products or their derivatives in the skin and (c) miscellaneous, poorly understood cutaneous complications of plasmacytic disorders. Lesions arising primarily in the skin and those due to cutaneous involvement by multisystem disorders are addressed. The range includes a spectrum of tumefactive and circulatory manifestations. We highlight key clinical and pathological features of the different conditions and outline recent advances in our understanding of these entities. By emphasizing the dermatopathological characteristics of this spectrum of disorders we hope to hone the diagnostic accuracy of practitioners in the field.
1 INTRODUCTION
Plasma cells (PCs), the final products of B‐lymphocyte differentiation, are primed to secrete antibodies against pathogenic antigens and they form one of the cornerstones of the immune system. Recognizable cytomorphologically by an eccentric “clock‐face” nucleus and amphophilic cytoplasm, PCs express CD79a and CD138 immunohistochemically (IHC), the latter being most specific, while they normally lack CD20. Individual PCs express kappa (κ) or lambda (λ) light chains, the small polypeptide subunits of immunoglobulin molecules. Reactive plasmacytic proliferations are polytypic, expressing proportionate amounts of both light chains, while neoplastic proliferations are monotypic, displaying light chain restriction (κ:λ ratio > 10:1 or λ: κ ratio > 4:1 [numbers agreed by most authors issuing from the “normal” κ:λ ratio of 2:1]). Plasmacytic (or lymphoplasmacytic) pathology can affect the skin (a) directly, by cutaneous plasmacytic infiltrates, (b) indirectly, by deposition of plasma cell products (or their derivatives) in the skin and (c) enigmatically, by a number of rare cutaneous complications and syndromes linked to paraproteinemias [Table 1].
| Direct (plasmacytic infiltrates) | Indirect (deposits) | Enigmatic (miscellaneous) | |
|---|---|---|---|
| Inflammatory | Neoplastic | Inflammatory or neoplastic disease | Paraprotein‐associated complications |
| Admixed plasma cellsa |
Admixed plasma cells
| Immunoglobulins and derivatives
| Cutaneous manifestations
|
Prominence of plasma cells
|
Predominance of plasma cells
| Multisystem syndromes
| |
- Abbreviations: AL, amyloid light chain; cMZL, cutaneous marginal zone lymphoma; IgG4‐RD, IgG4‐related disease; NXG, necrobiotic xanthogranuloma.
- a The list of conditions under this heading represents examples of relevant entities, it is not intended to be comprehensive.
- b In general, inflammatory disorders affecting mucosal sites and skin of the genitalia and head/neck contain admixed plasma cells.
- c In certain settings plasma cells serve as a diagnostic clue, for example, palisading granulomata—necrobiosis lipoidica; subtle vascular proliferations—Kaposi's sarcoma. They are also an expected finding in the background of Rosai‐Dorfman disease.
- d Three categories of scleredema exist: type 1 associated with certain acute infections; type 2 associated with a paraproteinemia; type 3 associated with diabetes mellitus.
2 PLASMACYTIC INFILTRATES IN THE SKIN—INFLAMMATORY
2.1 Admixed plasma cells
Non‐neoplastic conditions in which PCs, admixed with other cell types, form part of a general reaction pattern are numerous and notable examples include (a) infections (particularly syphilis and borreliosis), (b) connective tissue diseases (particularly morphea and lupus erythematosus), (c) the follicular occlusion tetrad (following follicular rupture) and (iv) inflammatory processes affecting special sites [mucosal surfaces (apart from plasmacytosis mucosae) and skin of the genitalia and head/neck (so‐called plasma cell‐friendly environments)].1 Moreover, PCs can serve as a diagnostic clue in certain settings for example, palisading granulomata (necrobiosis lipoidica) and subtle vasoproliferative disorders (Kaposi's sarcoma). Reactive PCs are also an expected finding in the background of Rosai‐Dorfman disease. These points notwithstanding, a comprehensive overview if this disease subset is beyond the scope of the current review.
2.2 Prominence of plasma cells
Inflammatory processes in which PCs form a prominent component of the infiltrate and play a key role in the pathological process include (a) multisystem disorders capable of involving the skin and (b) isolated cutaneous phenomena. “Cutaneous and systemic plasmacytosis,” multicentric Castleman's disease and IgG4‐related disease belong in the first group. These are rare chronic, systemic, inflammatory disorders of unknown etiology, characterized by a polyclonal lymphoplasmacytic proliferation, hypergammaglobulinemia and plasma cell‐rich tumefactive lesions at multiple anatomic sites. Although considered separate entities, overlap exists between them, occasionally leading to diagnostic quandaries.
Cutaneous plasmacytosis2-5 mainly affects adult Asian males and is characterized clinically by widespread non‐scaly, erythematous/brown plaques on the trunk and head/neck. Microscopically the lesions display mature, polytypic, plasma cell‐rich cutaneous infiltrates in perivascular, interstitial and perineural distributions. A polyclonal hypergammaglobulinemia is usually present. Sometimes accompanied by systemic manifestations and superficial lymphadenopathy, distinction between cutaneous and systemic plasmacytosis (defined by involvement of at least 2 organs) is challenging. This has prompted use of the term “cutaneous and systemic plasmacytosis”. A potential to evolve to lymphoma has been postulated.3, 4
Castleman's disease (CD),6, 7 first described as localized mediastinal lymphadenopathy or giant lymph node hyperplasia, is an uncommon, episodic, polyclonal lymphoplasmacytic disorder. Uni‐ and multi‐centric variants of the disease exist and histopathological subsets include the (a) hyaline‐vascular (b) plasma cell and (c) mixed types. Pertinent to this review is the multicentric, plasma cell subset. This may be idiopathic or HIV‐related and is characterized by lymphadenopathy, systemic symptoms, laboratory abnormalities (including polyclonal hypergammaglobulinemia) and rare involvement of extra nodal sites such as the skin. Cutaneous involvement results in multiple erythematous/brown plaques or nodules on the trunk, face and extremities. Microscopically these exhibit regressive lymphoid follicles with interfollicular plasmacytosis in the dermis/subcutis. Interleukin‐6 (IL‐6) and human herpesvirus‐8 (HHV‐8) have been implicated in the pathogenesis of the disorder. Affected patients are at risk for the development of lymphomas, Kaposi's sarcoma and/or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein & skin changes syndrome).
IgG4 related disease (IgG4 RD),8 a unifying term for a number of previously recognized organ specific diseases (eg, Riedel's thyroiditis, autoimmune sclerosing pancreatitis and others), is a rare, multisystem chronic inflammatory disorder of unknown etiology. It is characterized by tumefactive inflammatory lesions often affecting the hepatobiliary tree, the salivary glands, the lacrimal glands/orbits, lymph nodes and less commonly other organs including the skin. The histopathological hallmarks of the disease include a dense, polyclonal, lymphoplasmacytic infiltrate with enrichment of IgG4‐positive cells, storiform fibrosis and an obliterative phlebitis. In addition to cutaneous pseudolymphomas, granuloma faciale has been invoked as a manifestation of IgG4 RD,9 although a definite link with systemic disease remains to be proven. Elevated serum IgG4 levels and other polyclonal immunoglobulin abnormalities are usually present and the diagnosis requires clinicopathologic correlation.
In contrast to the systemic conditions outlined above, the entity termed “pretibial lymphoplasmacytic plaque in children” is an isolated cutaneous phenomenon.10, 11 It is characterized by a chronic, irregular, erythematous or tan‐brown plaque on the shin of an otherwise healthy Caucasian child or adolescent. The microscopic findings include a dense nodular to diffuse polytypic PC infiltrate in a lymphohistiocytic background. Lesions formerly referred to as acral pseudolymphomatous angiokeratoma of children (APACHE) likely belong in this category.12 Its etiology and course remain obscure.
3 PLASMACYTIC INFILTRATES IN THE SKIN—NEOPLASTIC
3.1 Admixed plasma cells
Admixed mature neoplastic PCs are observed in a number of low grade B‐cell lymphomatous infiltrates in the skin, be they of primary cutaneous or systemic origin. Examples, the most important of which is primary cutaneous marginal zone lymphoma (cMZL), are discussed here. Although the nature (reactive or neoplastc) of cMZL has been controversial, it is now classified as a low‐grade B cell lymphoma.13, 14 PCs are observed to varying degrees in this setting resulting in a heterogenous morphological spectrum. Some authors have found it useful to segregate cMZL into different sub‐types (conventional, lymphoplasmacytic, plasmacytic and blastoid variants).15 Using this scheme, admixed PCs are usually observed in the conventional (Figure 1) and lymphoplasmacytic variants of cMZL, while they tend to be prominent in the other variants. Mature neoplastic PCs may also be seen in primary cutaneous follicle center cell lymphomas, although this is the exception rather than the rule. They can also feature in instances of cutaneous involvement by systemic B‐cell lymphomas of which one example is lymphoplasmacytic lymphoma (LPL).16This neoplasm of small B lymphocytes, plasmacytoid lymphocytes and plasma cells primarily involves bone marrow, sometimes lymph nodes and the spleen. It is often associated with a paraprotein, usually IgM, and Waldenstrom's macroglobulinemia occurs in a subset of these patients. Demonstration of a monotypic PC infiltrate in a cutaneous deposit of LPL will indicate the neoplastic nature of the process and exclude a pseudolymphoma. Moreover the finding of an MYD88 L265P mutation in this setting is a helpful diagnostic clue, as this has been found in the majority of cases LPL/Waldenstrom's macroglobulinemia17 and only rarely in cMZL.
Clinical photographs of a young woman with cutaneous marginal zone lymphoma, conventional variant (cMZL[conv]) displaying an erythematous/tan nodule on the posterior aspect of the right shoulder (A and B). Microscopically cMZL (conv) is characterized by a dense nodular lymphocytic dermal infiltrate, with heterogenous light and dark zones reflecting populations of marginal zone cells with admixed plasma cells, and lymphocytes (C: H&E ×20). The mature plasmacytic component of the infiltrate is illustrated at high magnification (D. H&E ×400) and on immunohistochemistry it exhibits kappa light chain restriction (E and F. kappa & lambda ×40)
3.2 Predominance of plasma cells
Cutaneous infiltrates composed purely of neoplastic PCs may be categorized cytomorphologically as those comprising (a) atypical/plasmablastic cells and (b) bland/mature PCs. Involvement of the skin by multiple myeloma or by a systemic plasmablastic lymphoma feature in the first category while cMZL, plasmacytic variant, is the main consideration in the second (Figure 2).
This montage compares and contrasts two different plasmacytic skin lesion (i) cutaneous involvement by multiple myeloma (A‐D) and (ii) cMZL, plasmacytic (pl) variant (E and F). In the first instance, the extra medullary involvement by multiple myeloma is characterized clinically by a violaceus nodule on the anterolateral aspect of the right ankle (A and B). Microscopically such lesions display a dense nodular infiltrate of immature plasma cells in the skin/subcutis (C: H&E ×10). At high magnification plasmablastic cytological features are evident (D: H&E ×400). In contrast, cMZL(pl), though also consisting of a dense monomorphous dermal infiltrate of plasma cells (E: H&E ×20), shows mature plasma cells at high magnification (F: H&E ×400)
In multiple myeloma, the neoplastic PCs are dependent on the bone marrow microenvironment for survival and growth.18 Hence, extramedullary involvement is uncommon.19-21 The skin is affected in less than 2% cases, usually late in the course of the disease when the tumor burden is heavy. Most affected patients die within months. Clinically, the process is characterized by widely disseminated violaceous nodules or plaques. Microscopically, the infiltrates can have a nodular or diffuse interstitial pattern and they are composed of atypical PCs, often with a plasmablastic (and rarely a spindled pseudosarcomatous) cytomorphology. CD138 expression is retained and light chain restriction aligns with that of the primary disease. Histopathologically the lesions are indistinguishable from cutaneous involvement by a plasmablastic lymphoma, an aggressive, sub‐type of large B‐cell lymphoma often associated with HIV infection.22 Hence, integration of clinical and ancillary laboratory data is required for specific diagnostic purposes.
The reported prevalence of plasma cell‐rich subsets of cMZL has varied but, in one European center, the plasmacytic variant accounted for approximately 3% of cases.15, 23 There, it occurred in elderly patients and was characterized by one or more erythematous/brown plaques or nodules on the lower extremities. Microscopically the lesions exhibited a dense nodular to diffuse dermal/subcutaneous infiltrate of mature, monotypic plasma cells. Formerly regarded as “primary cutaneous plasmacytoma” or “extramedullary plasmacytoma,” these lesions are now recognized as a subset of cMZL.
4 DEPOSITION OF PLASMA CELL PRODUCTS AND THEIR DERIVATIVES IN THE SKIN
Indirect mechanisms of plasmacytic cutaneous pathology involve deposition of plasma cell products (immunoglobulins or their derivatives) in the skin, with varying consequences. Examples include cryoglobulin‐mediated vascular compromise, direct tumoral deposits of macroglobulins in the skin, abnormal storage of immunoglobulins in cutaneous histiocytes (crystal storing histiocytosis) and cutaneous AL amyloidosis.
4.1 Cryoglobulins
Cryoglobulins, alone or as part of an immune complex, reversibly precipitate at temperatures <37° centigrade, a condition which tends to prevail at acral sites. Two families of cryoglobulins exist: (a) type I—composed purely of monoclonal immunoglobulins, typically a consequence of a neoplastic lymphoplasmacytic proliferation (e.g. monoclonal gammopathy of uncertain significance [MGUS] or Waldenstrom's macroglobulinemia) and (b) types II and III—comprising mixed polyclonal immunoglobulins bound in immune complexes and typically associated with inflammatory conditions (eg, hepatitis C infection and connective tissue diseases).24 The monoclonal cryoglobulins24, 25 produce a hyperviscosity syndrome, reflected in the skin by Raynaud's phenomenon, acrocyanosis and livedo reticularis. A skin biopsy in the latter setting will reveal intraluminal, eosinophilic, refractile deposits of immunoglobulins within capillaries, in the absence of a vasculitis. These can be highlighted by a PAS stain. In contrast, polyclonal (mixed) cryoglobulin‐related immune complexes form deposits in vessel walls, activate complement and lead to a leukocytoclastic vasculitis. This is manifested clinically by palpable purpura at dependent sites, and microscopically by a neutrophilic angiodestructive small vessel vasculitis. Intraluminal cryoglobulin deposits are not usually observed in this setting.
4.2 Macroglobulins
Cutaneous macroglobulinosis results from deposition of IgM macroglobulins in the skin of a patient with Waldenstrom's macroglobulinemia or another IgM‐related paraproteinemia.26-28 It is characterized by flesh‐colored papules, mainly affecting acral sites. Microscopically, the lesions are characterized by amorphous deposits of hyaline material in the dermis. These are PAS‐positive, Congo red‐negative and they express IgM on IHC. The lesions may occur at any stage in the course of the disease and can precede the diagnosis.
4.3 Crystal storing histiocytosis
Crystal storing histiocytosis, a rare poorly understood microscopic phenomenon, can be observed in different organs.29-32 Usually a harbinger of lymphoplasmacytic or plasmacytic neoplasia with overproduction of immunoglobulins (mainly κ), it can also occur in inflammatory settings. Characterized by abnormal storage of non‐refractile, non‐polarizable immunoglobulin crystals in the cytoplasm of histiocytes, the bloated cells with abundant eosinophilic cytoplasm can lead to a misdiagnosis of rhabdomyoma or granular cell tumor. The latter pitfall occurred in the illustrated case of a pseudolymphoma of the scalp from a patient with IgG4 RD30 (Figure 3).
The clinical image of this cutaneous violaceus nodule, representing a pseudolymphoma on the scalp in a patient with IgG4‐related disease, is reproduced by kind permission of Elsevier [previously published in Diagnostic Histopathology, 2013; 19: 147‐150] (A). Microscopically the nodule is characterized by a dense heterogenous, dermal and subcutaneous cellular infiltrate (B: H&E ×10) exhibiting reactive lymphoid follicles (C: H&E ×40) and interstitial infiltrates of plump immunoglobulin‐laden histiocytes (crystal‐storing histiocytosis) admixed with plasma cells (D: H&E 400). The histiocytes display positivity for PAS (E: Pas‐D ×400) and they express CD 68 immunohistochemically (F: CD68 ×400)
4.4 AL amyloid (systemic)
Deposition of light chain‐related amyloid (AL) in the skin, usually a consequence of underlying systemic lymphoplasmacytic neoplasia or a plasma cell dyscrasia, should prompt systemic investigation.33, 34 A protein mis‐folding disorder, whereby excessive circulating light chains are converted to insoluble amyloid deposits, it is capable of involving any organ. Systemic AL amyloidosis, due to a small but lethal clone of plasma cells in the bone marrow, causes cutaneous amyloid deposition in approximately 15% of cases. Clinically it is characterized by macroglossia, periorbital purpura and waxy cutaneous plaques at various sites. Microscopically, deposits of pale eosinophilic amorphous material are seen in blood vessel walls and in the interstitium of the dermis/subcutis. These are congophilic, with apple green birefringence under polarized light. Determination of the precursor protein, light chains in this instance, is most reliably performed by laser microdissection and mass spectrometry.35
4.5 AL amyloid (cutaneous)
Rarely AL amyloid deposits occur in the skin/subcutis in the absence of systemic disease (Figure 4). Referred to as AL amyloidomas or localized nodular amyloidosis these lesions are characterized clinically by tan, waxy nodules or plaques on the extremities of older patients.36 Microscopically, the amorphous amyloid deposits occupy the dermis/subcutis, with thickening of blood vessel walls. Occasionally there is dystrophic calcification/ossification. A sparse monotypic plasmacytic infiltrate is usually present. The nosologic status of these lesions has been obscure, but recent evidence suggesting that they are unusual manifestations of cMZL includes (a) the monotypic character of the plasmacytic infiltrate, (b) repeated local recurrences of the lesions, (c) development of the lesions in patients with concurrent or subsequent cMZL, (d) shared genetic abnormalities between the lesions and cMZL and (e) the analogy between these lesions and peritumoral amyloidomas associated with MALT lymphomas of the lung and breast.
This cutaneous AL amyloidoma (now considered an unusual manifestation of cMZL), is characterized clinically by a tan waxy plaque on the anterior aspect of the right lower leg (A). Microscopically such lesions show expansion of the dermis by homogenous eosinophilic material (amyloid) with rare cellular clusters (B: H&E ×10). At higher magnification amyloid deposition is observed interstitially and concentrically around blood vessels, accompanied by a light perivascular plasma cell‐rich infiltrate (C: H&E ×40). Intramural vascular deposition of amyloid is also evident (D: H&E ×100). The plasma cells, in this context, display kappa light chain restriction, as expected in the setting of AL amyloid deposition (E and F: kappa & lambda ×100)
5 PARAPROTEIN‐ASSOCIATED COMPLICATIONS
Paraproteinemias are characterized by the presence of circulating monoclonal immunoglobulins produced by an abnormal clone of plasma cells. They are observed in low‐grade lymphoplasmacyitc neoplasms and in plasma cell dyscrasias. The underlying proliferative disorder can begin as an indolent process and progress to frank malignancy. Although prone to development of certain cutaneous complications and multi‐system syndromes, the pathogenetic link between the paraprotein and these sequelae is obscure.
5.1 Cutaneous complications of paraproteinemias
Diffuse normolipemic plane xanthomas are one example of a paraprotein‐related cutaneous complication.37-40 Characterized clinically by asymptomatic, symmetrical, yellow/brown patches and plaques, usually on the trunk and sides of the neck, the lesions display dermal infiltrates of foamy macrophages microscopically. These are a consequence of phagocytosis of immune complexes comprised of the abnormal circulating immunoglobulins and low‐density lipoproteins. The lesions can occur at any time in the course of a lymphoplasmacytic disorder and can be the harbinger of the disease.
Scleredema, observed in different clinical settings, is categorized accordingly (eg, type 1—certain acute infections, type 2—paraproteinemias and type 3—diabetes mellitus).41-44Affected patients develop woody induration and thickening of the skin of the back, neck, face and chest. Microscopically, there is thickening of the dermis with enlargement of collagen bundles and increased interstitial mucin deposition. The pathogenesis of the disorder is unknown, its course varies with the precipitating cause and extra‐cutaneous involvement is rare.
5.2 Syndromes associated with paraproteinemias
Syndromes associated with paraproteinemias include scleromyxedema,45, 46 necrobiotic xanthogranuloma,47 Schnitzler's syndrome48, 49 and POEMS syndrome.50-52 An outline of these entities is provided in Table 2. Briefly, these rare, poorly understood, chronic conditions affect middle aged to older adults and are associated with significant morbidity and mortality. A clear role for the abnormal paraprotein in the pathogenesis of these disorders has not been elucidated. Certain cytokines (eg, interleukin‐1β in Schnitzler's syndrome) have been implicated in promoting the disease process. To date, management of these syndromes has been empiric, employing strategies to reduce circulating immunoglobulins (corticosteroids, chemotherapeutic agents, plasmapheresis and intravenous immunoglobulins) and targeted anti‐inflammatory agents. Dermatopathologists can play a key role in identifying the cutaneous manifestations of these syndromes.
| Syndrome | Cutaneous features (clinical) | Cutaneous features (pathological) | Non‐cutaneous features (any or all) |
|---|---|---|---|
| Scleromyxedema | Papular eruption (widespread/sclerodermoid) | Mucin/fibroblasts/fibrosis (upper 2/3 of dermis) |
|
| NXG | Plaques/nodules, indurated and yellowish (trunk/extremities/periorbital) | “Necrobiotic” granulomas, foamy histiocytes +/−, cholesterol clefts +/− (dermis and subcutis) |
|
| Schnitzler's syndromea | Urticarial rash, recurrent (trunk/extremities) | Neutrophilic dermal infiltrate (light perivascular and interstitial) |
|
| POEMS syndromeb | Glomeruloid hemangiomas (GH) (red/purple papules, trunk and proximal extremities) Other (hyperpigmentation, acrocyanosis or plethora, hypertrichosis, white nails) | GH (dermal ectatic vascular spaces filled with glomerulus‐like clusters of capillaries) |
|
- Abbreviations: CRP, c‐reactive protein; ESR, erythrocyte sedimentation rate; NXG, necrobiotic xanthogranuloma; POEMS syndrome, polyneuropathy, organomegaly, endocrinopathy, M protein & skin changes.
- a Strasbourg criteria for a diagnosis of Schnitzler's syndrome: Obligate criteria—chronic urticarial rash and IgG or IgM monoclonal gammopathy; Minor criteria—recurrent fever, abnormal bone re‐modeling (on X‐ray), neutrophilic dermal infiltrate, leukocytosis and/or elevated CRP. Definite diagnosis—two obligate criteria and at least two minor criteria if IgM, and three minor criteria if IgG. Probable diagnosis—two obligate criteria and at least one minor criterion if IgM, and two minor criteria if IgG.
- b POEMS syndrome. Diagnostic criteria include: Major criteria—polyneuropathy and monoclonal plasmaproliferative disorder. Minor criteria—sclerotic bone lesions, Castleman's disease, organomegaly, edema, endocrinopathy, skin changes, papilledema. Diagnosis—two major criteria and at least one minor criterion.
6 ADVANCES IN OUR UNDERSTANDING OF LYMPHOPLASMACYTIC PATHOLOGY
Over time, our understanding of most subsets of plasmacytic pathology has improved. Although etiologic factors often remain elusive, clarification of disease mechanisms has emerged. For example, the causes of systemic plasmacytosis, multicentric Castleman's disease and IgG4‐related disease are unknown but many of the relevant inflammatory pathways have been identified.2, 7, 8 This has helped to hone therapeutic strategies. Whether the overlap that exists between these conditions signifies a unifying theme remains to be determined. Moreover, their potential to evolve to lymphoplasmacytic neoplasia deserves further study.
Unanswered questions about plasma cell dyscrasias remain but some clarifications have emerged. Often considered a low grade, innocuous process, MGUS, characterized by laboratory evidence of a monoclonal immunoglobulin in the serum or urine of an asymptomatic patient, is observed in approximately 3% of older adults.53, 54 Experience has shown that the underlying plasma cell clone can evolve to frank malignancy, culminating in multiple myeloma in approximately 1% of cases. In addition the nature of the circulating immunoglobulin is important. Sometimes inactive, the protein can alternatively be a noxious substance capable of (a) forming tissue deposits and organ damage or (b) obstructing blood vessels leading to circulatory disturbances. Hence, the true “significance” of MGUS should not be underestimated.
Important advances have followed our improved understanding of cMZL and its variants.15Skin lesions previously regarded as immunocytomas, cutaneous plasmacytomas or extramedullary plasmacytomas are now interpreted as cMZL, plasmacytic variant. Similarly, AL amyloidomas of the skin (with monotypic plasma cells) are now recognized as unusual manifestations of cMZL. In both instances, the switch in nosologic status from a putative “plasma cell dyscrasia” to an indolent primary cutaneous B cell lymphoma has important prognostic implications. Hopefully, ongoing studies of patients with different plasmacytic disorders will clarify outstanding enigmas and improve therapy.t
ACKNOWLEDGEMENTS
The authors gratefully acknowledge Mr Stephen Whitefield at Dalhousie University who shot some of the photomicrographs and collated all of them. They also appreciate the clerical support of Ms Patsy Morgan at the NSHA. They are grateful too to Elsevier for permission to reproduce Figure 3A, previously published in Diagnostic Histopathology 2013; 19: 147‐150.
CONFLICT OF INTEREST
The authors declare no potential conflict of interest
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