Fibi Ninan, Ajay Kumar Mishra, Ajoy Oommen John, Iyadurai Ramya Department of General Medicine, Christian Medical College, Vellore, Tamil Nadu, India
Multiple myeloma is a neoplasm that occurs due to monoclonal proliferation of plasma cells. Anemia, hypercalcemia, renal failure, and osteolytic lesions are the common manifestations. Less than 5% of patients present with extramedullary dissemination at the time of diagnosis. The common sites of extramedullary dissemination are liver, spleen, adrenals, and lung. Spread of myeloma into retroperitoneum causing retroperitoneal fibrosis is one of the rare manifestations. Patients with disseminated myeloma are usually young and have a poor disease-free survival rate. Aggressive therapy in the form of stem cell transplant has shown to be of benefit in such patients.
Keywords: Extramedullary dissemination of myeloma, multiple myeloma, retroperitoneal fibrosis
Multiple myeloma is a hematological malignancy which occurs secondary to uncontrolled monoclonal proliferation of plasma cells. The disease usually remains confined to the skeleton and bone marrow, and the clinical manifestations are secondary to tissue or organ impairment, namely, hypercalcemia, anemia, renal failure, and bony pains. Extraosseous manifestations are seen only in <5% of the patients. These include peritoneal carcinomatosis, pelvic sclerosis, deposits in intraabdominal organs such as liver and spleen.
We report a case of multiple myeloma with extramedullary dissemination manifested as anemia and retroperitoneal fibrosis.
A 44-year-old serviceman with no prior comorbidities presented with low-grade fever for 4 months associated with significant loss of weight and appetite. He had excessive fatigue and dyspnea on exertion. On examination, he had a normal blood pressure and pulse rate. His jugular venous pulse was elevated, and there was significant pallor. Cardiovascular examination was normal. Examination of the abdomen revealed hepatomegaly with liver palpable 4 cm below the costal margin, with smooth margins and regular borders. Remainder of his clinical examination was normal.
The differentials considered for anemia, hepatomegaly with loss of weight, and appetite were solid-organ malignancies, myeloproliferative syndromes, and disseminated tuberculosis.
On evaluation, he was found to have severe anemia with a hemoglobin of 2.9 mg/dL (ref range: 14–16 mg/dL). Iron studies were suggestive of iron deficiency anemia with a mean corpuscular volume of 69.8 fL (ref range: 80–96 fL) and ferritin of 5.6 ng/mL (ref range: 20–320 ng/mL). Other cell lines were normal with a total count of 4600 mm  (ref range: 4000–12,000 mm ) and platelet count of 289,000 mm (ref range: 150,000–450,000 mm ). His liver function tests showed normal bilirubin and liver enzymes with reversal of albumin/globulin ratio (total protein: 8.4 mg/dL; albumin: 2.1 mg/dL). Hence, a differential diagnosis of plasma cell disorder was considered and a bone marrow examination was done which showed features of multiple myeloma with 22% plasma cells. M band was present on serum electrophoresis (3.2 g%) and there was hypercalcemia with a corrected calcium of 11.42 mg/dL (ref range: 8.3–10.4 mg/dL). The Bence-Jones protein urine test was negative and skeletal survey did not reveal any lytic lesions in the bone. Serum immunoglobulin M (IgM) was 4941 mg% (ref range: 50–190 mg%). Stool occult blood was positive. Esophagoduodenoscopy and colonoscopy done to rule out gastrointestinal malignancies were normal. Computed tomography thorax and abdomen showed moderate hepatomegaly and features of retroperitoneal fibrosis throughout the length of the aorta and proximal common iliac vessels, encasing the retroperitoneal vessels and ureters [Figure 1] and [Figure 2]. IgG4 disease was considered, but the serum IgG4 levels were low. Magnetic resonance imaging-guided biopsy of the retroperitoneal tissue was done which showed fibroadipose and fibrocollagenous tissue with vascular proliferation and a lesion composed of dense aggregates of predominantly mature plasma cells which was suggestive of extramedullary dissemination of multiple myeloma.
Multiple myeloma occurs secondary to malignant proliferation of monoclonal plasma cells which produce Igs. In India, the incidence of multiple myeloma varies from 1.2–1.8 per 100,000 population and approximately 50,000 patients are newly diagnosed each year.
Multiple myeloma is predominantly the disease of the elderly, seen in fifth and sixth decades with the mean age of 64 years at the time of diagnosis. There are few reports of multiple myeloma in patients <40 years as it was in our patient. However, they have a better prognosis with longevity twice as longer than their older counterparts.
Plasma cell disorders present with varying clinical manifestations. Anemia due to infiltration of marrow with plasma cells, proteinuria secondary to circulating monoclonal antibodies, renal tubular damage, and osteolytic lesions in the bone due to osteoclast activation with secondary hypercalcemia are common disease manifestations. Severe anemia with excessive fatigue was the presenting complaint in our patient.
Multiple myeloma which is usually confined to the skeletal system can involve extramedullary sites. This can be due to extramedullary plasmacytoma or due to extramedullary dissemination of multiple myeloma. Extramedullary plasmacytoma is characterized by monoclonal plasma cells in histology, absence of bony lytic lesions, insignificant M band, absence of hypercalcemia or renal failure, and <5% of plasma cells in bone marrow. Extramedullary dissemination is seen in 15%–20% patients at the time of diagnosis when the myeloma spreads from the bone marrow to other organs of the body. The exact mechanism of dissemination is not known. However, it has been postulated that decreased expression of adhesion molecules facilitate dissemination of plasma cells to rest of the body. This can be either by direct extension through ruptures in cortex of bone or through hematological spread.
The common sites of extramedullary dissemination are liver, spleen, adrenals, ovary, lung, pericardium, and gastrointestinal tract. There are only few case reports of extramedullary dissemination of multiple myeloma causing infiltration of the peritoneum. Sinapi et al. reported retroperitoneal fibrosis in a 59-year-old gentleman with IgG lambda multiple myeloma. The exact mechanism of retroperitoneal fibrosis in multiple myeloma is not known; however, it is probably due to expression of inflammatory mediators by plasma cells. Multiple myeloma can also cause amyloid deposits in the retroperitoneum leading to retroperitoneal fibrosis. In our patient, biopsy of the retroperitoneal fibrous tissue showed fibrocollagenous tissue with plasma cells which was suggestive of infiltration of the disease into extramedullary region.
Various studies have shown that patients with extramedullary spread of multiple myeloma are usually young and had shorter survival when treated with conventional therapy., However, the survival rate was comparable when these patients underwent autologous stem cell transplant. This reiterates the importance of evaluation for an extramedullary spread in patients with multiple myeloma to offer aggressive therapy and better survival.
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