Myelomatous pleural effusion and extensive extraskeletal soft tissue involvement: a rare presentation of clonal plasma cell disorders

Abstract

A 65-year-old woman presented with a history of progressive dyspnoea, left pleuritic pain, loss of weight and appetite. Previous history was significant for pulmonary tuberculosis diagnosed 10 years before. Physical examination revealed a left supraclavicular soft tissue mass with absent breath sounds over the left hemithorax. Investigations revealed hypercalcemia with albumin:globulin reversal. The bone marrow biopsy was consistent with the diagnosis of multiple myeloma (IgG). Pleural fluid analysis revealed an exudative effusion; cytology showed mature plasma cells and plasmablasts. Serum electrophoresis revealed an M band in the gamma region. Biopsy of the supraclavicular mass revealed plasma cells which were CD 138+ with Kappa light chain restriction. She was initiated on chemotherapy and is currently doing well. Myelomatous pleural effusion is a rare presentation of multiple myeloma.

Background

Multiple myeloma is a clonal plasma cell dyscrasia which presents with a wide spectrum of clinical manifestations due to involvement of multiple organ systems.¹ Pleural effusion presenting as the initial manifestation of multiple myeloma is a rare entity. True myelomatous pleural effusion, which results from direct infiltration of the pleural space by plasmacytes, is even rarer. We present a case of multiple myeloma with a massive pleural effusion being the index presentation, and later diagnosed as a true myelomatous pleural effusion.²

Case presentation

A 65-year-old woman presented to our centre with breathing difficulty, cough, left-sided pleuritic pain, lower backache, with loss of weight and appetite for 7 months. There was no history of fever. Previous history was significant for pulmonary tuberculosis 10 years before, which was declared cured following 6 months of antituberculous therapy. Examination revealed tachycardia, tachypnoea, engorged neck veins and respiratory distress. She had a 5×5 cm, firm, subcutaneous mass in the left supraclavicular region. Respiratory system examination revealed absent breath sounds over the left haemithorax. Rib tenderness was noted along the fifth, sixth and seventh ribs. Scoliosis was observed with spine tenderness corresponding to D12–L4 vertebrae.

Investigations

Differential diagnoses considered were disseminated tuberculosis, metastatic malignancy, multifocal Castleman’s disease and a lymphoproliferative neoplasm. Investigations revealed anaemia with haemoglobin—94 (N: 110–150) g/L, total protein—12.1 (N: 6.0–8.0) g/dL, albumin—3.9 (N: 3.5–5.0) g/dL, calcium—11.34 (N: 8.3–10.4) mg/dL, creatinine—1.22 (N: 0.7–1.4) mg/dL, serum lactate dehydrogenase (LDH)—775 (N:225–460) U/L and pleural fluid LDH—537 U/L. Chest X-ray showed moderate left-sided pleural effusion. The reversal in albumin:globulin ratio and hypercalcemia prompted consideration of a plasma cell dyscrasia. Her investigations are as shown in table 1.

Table 1.

Summary of investigations in the patient

Test	Patient’s result	Normal range
Serum electrophoresis	M-band in γ—4.93 g	Negative
Urine Bence Jones protein assay	Positive	Negative
Free light chain assay (serum)
Kappa (κ) (mg/dL)	1214	3.3–19.4
Lambda (λ) (mg/dL)	33.12	5.7–26.6
κ/λ (ratio)	36.6
Immune fixation electrophoresis	IgG (κ)	Negative
β2microglobulin (mg/L)	16.68	0–3 µg/mL

Cross-sectional imaging of the thorax and abdomen showed soft tissue masses in the posterior mediastinum, left supraclavicular and paraspinal regions with adjacent muscular infiltration (figure 1A) and lytic lesions with soft tissue components in vertebrae, ribs, pelvis, femur, sternum, clavicle and scapula (figure 1B). Focal nodular plasma cell aggregates were demonstrated on bone marrow examination with 70% plasma cells, including plasmablasts (figure 1C).

Figure 1.

(A) Contrast-enhanced CT thorax showing enhancing soft tissue mass in posterior mediastinum and bilateral pleural effusion (L>R). (B) Contrast-enhanced CT thorax showing multiple lytic lesions in bilateral ribs, vertebral body, pedicle and transverse process. (C) Bone marrow biopsy showing of plasmablasts and plasma cells with eccentrically placed nuclei, prominent nucleoli and moderate eosinophilic cytoplasm.

Literature has shown that tuberculosis may coexist with multiple myeloma, owing to profound immunosuppression caused by the latter. A pleural fluid analysis was performed, followed by a biopsy from the left supraclavicular mass, to differentiate between a true myelomatous effusion or an infective aetiology. An exudative effusion (based on Light’s criteria—pleural LDH/serum LDH=0.69 with pleural LDH greater than two-thirds of the upper limit of normal) was seen on pleural fluid analysis with cytology showing atypical plasma cells. Cultures and M.Tb PCR on the sample tested negative. Ultrasound-guided biopsy of the supraclavicular soft tissue mass showed sheets of atypical polygonal plasma cells that were CD-138 positive with κ—light chain restriction suggestive of plasma cell myeloma. The final diagnosis was IgG κ multiple myeloma with true myelomatous pleural effusion (International Staging System (ISS) stage III).

Treatment

The patient was initiated on combination chemotherapy (cyclophosphamide, bortezomib and dexamethasone) with bisphosphonates and is doing well on follow-up. Chest X-ray after two cycles of chemotherapy, as compared with baseline X-ray (figure 2A), demonstrated complete resolution of the effusion (figure 2B).

Figure 2.

Chest radiographs (A) before and (B) after induction chemotherapy.

Outcome and follow-up

The patient was continued on chemotherapy and is clinically asymptomatic at 7 months of follow-up.

Discussion

Multiple myeloma can present with a wide spectrum of clinical manifestations secondary to direct infiltration of various organ systems by plasmacytes or light chains.¹ Pleural effusion is seen in a small proportion of these patients. Pleural effusion as the index presentation of myeloma is extremely rare.² Proposed mechanisms for the effusion include cardiac failure due to amyloidosis-related restrictive cardiomyopathy or hyperviscosity, light chain deposition-related nephritic syndrome, oliguric renal failure, synpneumonic effusion due to infections or a true myelomatous effusion due to pleural infiltration by plasmacytes.³ Riveiro et al reported a systemic review of 153 patients with a primary diagnosis of myeloma who developed a pleural effusion. This study reported a higher preponderance among men with a median age of 62 years. Commonly reported symptoms were bone pain (100%), dyspnea (98.8%) and chest pain (95.3%). Most cases had unilateral disease (63.9%) and involved more than two-thirds of the affected haemithorax (54.5%) at presentation.² Plasma cell dyscrasias cause an acquired immunodeficiency with increased predisposition to reactivation of latent infections such as tuberculosis.⁴ Some case reports have shown coexistence of tuberculosis with myeloma. Tsai et al conducted an observational study on the incidence of tuberculosis in patients with myeloma and matched controls. The risk of tuberculosis was significantly higher in patients with myeloma (HR 3.11, 95% CI 2.41 to 4.02).⁵ Literature has established the theoretical plausibility for coexistence of both diseases. In countries like India with a high prevalence of tuberculosis, this possibility must be considered and ruled out, as initiation of chemotherapy in patients with active tuberculosis can prove catastrophic.

In our patient, presence of plasma cells on pleural fluid cytology and histopathological evidence of myeloma confirmed a myelomatous pleural effusion. This report highlights the uncommon and complex presentation of a true myelomatous effusion which is of profound prognostic significance as these patients are noted to exhibit poor clinical outcomes and response to therapy.⁶ Despite available literature pointing to the contrary, a full resolution of the effusion was noted in our patient following combination chemotherapy.

Learning points.

• Pleural effusion presenting as the initial manifestation of multiple myeloma is a rare entity.

• The risk of tuberculosis is significantly higher in patients with myeloma.

• Patients with true myelomatous effusions are noted to exhibit poor clinical outcomes.

• Despite literature pointing to the contrary, a full resolution of the effusion was noted in our patient following combination chemotherapy.