Hemorrhagic Skin Nodules and Plaques: A Diagnostic Clue to Underlying Primary Plasma Cell Leukemia.

Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder characterized by a malignant proliferation of plasma cells (PC) in blood and marrow. Cutaneous involvement is very rare in PCL. We present the case of a 45-year-old lady who presented with multiple hemorrhagic nodules and plaques in the skin. Her total leucocyte count was 2,00,200/cmm with 85% abnormal plasmacytoid cells in peripheral smear. Biopsy of the skin lesions revealed diffuse infiltration by plasma cells with 'choked' blood vessels. A diagnosis of plasma cell leukemia with cutaneous involvement was made. On the second day of admission, the patient expired probably because of intracranial bleed due to thrombocytopenia. Post-mortem bone marrow and liver biopsy also showed diffuse infiltration by plasma cells. Monoclonality of the cells was proven by demonstrating the production of only kappa light chains.

What was known?

Plasma cell leukemia is known to have extramedullary involvement but skin involvement is rare and only one case has been reported with hemorrhagic skin nodules.

Introduction

Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder characterized by a malignant proliferation of PCs in blood and marrow, with a usual aggressive clinical course and poor outcome.[1] PCL has been defined as circulating peripheral blood plasma cells (PCs) exceeding >2000/mm3, with PCs also comprising greater than 20% of peripheral blood cells.[2] This is one of the most aggressive human neoplasms. Two types of PCL are recognized, primary or de novo and secondary to multiple myeloma.[3] In patients with primary PCL, PC infiltration frequently occurs in extramedullary sites such as internal organs, brain, and muscles. Cutaneous involvement is very rare in PCL.[1] We present a case of primary PCL, who presented with hemorrhagic cutaneous nodules and plaques.

Case Report

A 45-year-old female patient was admitted in our hospital with multiple painful swellings on both lower limbs associated with low-grade fever, cough, expectoration, and low backache of 1-month duration. Cutaneous examination revealed multiple, tender, erythematous nodules and plaques, measuring a few centimeters to a maximum of 20 cm × 15 cm in size, which were located in both lower limbs, abdomen, and shoulder. Some lesions had violaceous margins, and small ecchymotic foci on the surface [Figure 1a and b]. Systemic examination revealed severe pallor; no other specific finding was noted. The patient had visited the gynecology department OPD of our hospital a month back for menorrhagia of 1-week duration, for which endometrial curettage was done. No skin lesions were noted at that time. She had mild pallor at that time which was attributed to menorrhagia and was prescribed hematinics for that. Histopathology of the endometrium was reported as PC endometritis, but further investigations could not be carried out as the patient did not come for follow-up until this visit requiring admission.

Figure 1

(a) Two large cutaneous plaques on the hip, (b) multiple hemorrhagic cutaneous nodules on the forearm

Her hemogram performed at the present visit, when she developed many skin lesions, revealed hemoglobin of 3.7 gm% with normocytic normochromic red blood cells (RBCs) and platelet count of 44,000/cmm. Her total leucocyte count was 2,00,200/cmm, with differential count of 4% polymorphonuclear cells, 11% lymphocytes, and 85% abnormal plasmacytoid cells in peripheral smear [Figure 2a]. Many of the plasmacytoid cells had prominent nucleoli and basophilic cytoplasm and had the appearance of “flare cells” [Figure 2b]. Biopsy of the skin lesions revealed diffuse infiltration by PCs with “choked” blood vessels [Figure 3]. The patient was transfused with packed RBCs but almost 12 h later; she developed sudden onset altered sensorium, unresponsiveness to all stimuli, pupillary anisocoria, followed by cardiorespiratory arrest from which she could not be revived. Postmortem bone marrow and liver biopsy also showed diffuse infiltration by PCs. Monoclonality of the cells was proven by demonstrating the production of only kappa light chains [Figure 4]. Immunophenotype of these cells revealed negativity for CD45, CD20, CD3, and lambda light chains. A final diagnosis of primary PCL with secondary cutaneous involvement was made.

Figure 2

(a) Peripheral blood smear showing leukocytosis with many circulating plasma cells (Leishman, ×400), (b) higher magnification showing plasma cells with eccentric nuclei and amphophilic cytoplasm (Leishman, ×1000)

Figure 3

Skin biopsy showing a diffuse infiltration by atypical plasma cells. Inset shows a blood vessel “choked” with plasma cells (H and E, ×200)

Figure 4

Immunohistochemistry showing positive staining for kappa chain (left panel) and negative staining for lambda chain (right panel)

Discussion

Four types of plasma cell neoplasia are recognized: Classic multiple myeloma, extramedullary plasmacytoma without multiple myeloma, solitary plasmacytoma of bone, and PCL.[4] Cutaneous involvement may be seen in all four types of plasma cell neoplasia.[4]

PCL is a rare variant of multiple myeloma occurring in about 2% of newly diagnosed patients.[2] Manifestations occur in the form of cell lines failure; for example, anemia leading to fatiguability, leucopenia causing recurrent infections, and thrombocytopenia causing mucosal bleed. Diagnosis rests on identifying PCs on the peripheral smear, and the bone marrow examination, which are supported by serum electrophoresis. The treatment options are limited and have not been really able to alter the fatal outcome of the disease.

Clonal proliferations of PCs in tissues are called plasmacytomas.[5] These are usually localized tumors either in bone (osseous) or extramedullary sites.[5] Extramedullary involvement of spleen and liver are most common.[6] Other visceral sites of involvement include kidneys, lungs, heart, pleura, testes, skeletal muscles, central nervous system, and, very rarely, skin.[6] However, clinical manifestation of extraosseous PCL is not frequent at the time of initial diagnosis. The lack of the CD56 on the malignant PCs explains the reason for their spread into extramedullary sites as CD56 is considered to have an important role in anchoring PCs to the bone marrow stroma.[2]

Cutaneous involvement accounts for 4% of all extramedullary plasmacytomas.[5] Solitary and multiple extramedullary plasmacytomas of the skin may occur in association with soft-tissue plasmacytomas involving other organs or may form a part of the clinical manifestations of multiple myeloma.[7] The primary involvement of the skin without evidence of bone involvement is extremely rare, with only a handful of cases (less than 30 cases) recorded to date in the world literature.[5] Patients usually present with solitary or multiple, slowly growing violaceous dermal or subcutaneous nodules with no specific site predilection.[5] García-Sanz et al. noted cutaneous involvement in 3 out of 26 patients with primary PCL, and in all three patients the lesions were subcutaneous nodes.[8] Chattopadhyay et al.[2] reported a 52-year-old female patient with primary PCL presenting with multiple painful, tender, firm, nodular, and hemorrhagic swellings over arms, trunk and buttocks with a month-long history of low-grade fever, and fatigue.[2] Our patient also presented with multiple, tender, nodular, and hemorrhagic swellings in the skin.

In retrospect, we assume that the PC endometritis with mild pallor at first presentation was nothing but leukemic PC infiltration into the endometrium. However, with no other symptoms or signs, detailed work up might have clinched the diagnosis had the patient reported back for follow-up. The presence of severe pallor and skin lesions later pointed toward advanced stage of leukemia. We report this case for its rarity as the occurrence of hemorrhagic cutaneous nodules and plaques in primary PCL (as in our case) is an extremely unusual manifestation with just one previous report of a similar presentation.[2] However, the occurrence of such lesions in a patient who has features of blood cell lines failure should alert the treating physician regarding the possibility of a primary PCL.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

Hemorrhagic skin nodules and plaques in a patient with features of blood cell line failures should alert the physician about the possibility of PCL. Such presentation has been reported only once in literature.