Jorge Luiz de Carvalho Mello Deborah Pedrosa; Emilio Andrade Rocha; Juliana Monroe Silva; Sebastião Jupiaçara Guimarães
INTRODUCTION AND OBJECTIVE: Plasmacytoma is a neoplastic proliferation of a plasma cell clone which produces monoclonal immunoglobulin. Solitary plasmacytoma of bone is defined by the presence of a single plasmacytoma in the absence of multiple osteolytic lesions or other findings compatible with multiple myeloma. We report an older patient with solitary plasmacytoma of the sternum associated with atypical clinical findings which complicated diagnosis and possible progression to multiple myeloma.
CASE REPORT: A 74-year-old woman sought medical care due to mental confusion, tachydyspnea, and chest pain after a fall with blunt trauma to the anterior chest. During admission, the patient developed refractory hyponatremia, superficial thrombophlebitis in the left upper limb, periorbital cellulitis, endophthalmitis, and sternal osteomyelitis. Serum protein electrophoresis showed a polyclonal increase in gamma globulins. Biopsy result was compatible with plasmacytoma. A computed tomography scan showed no additional lesions. Progression was poor, with chronic renal failure exacerbated by probable tumor lysis syndrome, resulting in death.
CONCLUSION: The present findings emphasize the importance of considering a diagnostic hypothesis of plasmacytoma/multiple myeloma in older patients with a set of varied clinical signs, such as anemia, renal failure, pathological fracture, and repetitive infections.
Keywords: plasmacytoma; multiple myeloma; thrombophlebitis; hyponatremia.
INTRODUÇÃO E OBJETIVO: O plasmocitoma é uma proliferação neoplásica de um clone de plasmócitos que produzem imunoglobulina monoclonal. O plasmocitoma solitário ósseo é definido pela presença de um plasmocitoma na ausência de múltiplas lesões osteolíticas ou outros achados compatíveis com mieloma múltiplo. O presente artigo relata o caso de uma paciente idosa que apresentou plasmocitoma ósseo solitário de esterno de difícil diagnóstico devido a manifestações clínicas atípicas e possível evolução para mieloma múltiplo.
RELATO DO CASO: Paciente de 74 anos, do sexo feminino. Procurou atendimento médico por confusão mental, taquidispneia e dor torácica precordial em queimação, além de história de queda com trauma da região anterior do tórax. Na internação hospitalar evoluiu com hiponatremia refratária ao tratamento, tromboflebite superficial em membro superior esquerdo, celulite periorbitária, endoftalmite e osteomielite no esterno. A eletroforese de proteínas séricas teve como resultado o aumento policlonal na região das gamaglobulinas. A biópsia da lesão considerou achado compatível com plasmocitoma. Tomografia computadorizada de esqueleto não evidenciou lesões adicionais. Apresentou uma evolução ruim com insuficiência renal crônica agudizada por provável síndrome de lise tumoral, indo a óbito.
CONCLUSÃO: O estudo vem ressaltar a importância da hipótese diagnóstica de plasmocitoma/mieloma múltiplo frente a um paciente idoso, com manifestação clínica diversificada, como anemia, insuficiência renal, fratura patológica e infecções de repetição, em vista de sua evolução e prognóstico.
Palavras-chave: Plasmocitoma; mieloma múltiplo; tromboflebite; hiponatremia.
Solitary plasmacytoma (SP) is an uncommon type of plasma cell (PC) dyscrasia, accounting for approximately 2-5% of all PC disorders.1-3 SP is characterized by a proliferation of neoplastic monoclonal PCs without radiological evidence of bone lesions or CRAB features of multiple myeloma (MM), i.e., hypercalcemia, renal failure, anemia, and bone lesions, along with morphologically normal bone marrow or bone marrow containing less than 10% PC.4,5
SP can be classified as solitary plasmacytoma of bone (SPB) or extramedullary solitary plasmacytoma (ESP), depending on the origin of the lesion.6 The incidence of SPB is approximately 40% higher than that of ESP.3 SPB affects mostly males (1.2:1 to 2.0:1)3,6-10 and blacks.1,3,9 Mean age at diagnosis is 55-60 years. About 50% of patients with SPB will develop MM within 10 years.10 There is little research on this rare disease and no consensus on its prognosis and treatment.11
We report the case of an older women in whom diagnosis of SPB involving the sternum was complicated by atypical clinical manifestations. Possible progression to MM was not confirmed due to her death.
A 74-year-old woman was admitted to the hospital with mental confusion, tachydyspnea, and chest pain after a fall with blunt trauma to the anterior chest. Commorbidities included systemic hypertension with target organ lesions (heart failure, chronic renal failure not requiring dialysis), normochromic/normocytic anemia, and major depression. She showed no cognitive deficit and was functionally independent. She used the following medications: spironolactone 25 mg/day, metropolol 50 mg/day, olmesartan 40 mg/day, amlodipine 5 mg/day, epoetin alfa 3,000 UI once a week, escitalopram 15 mg/day, and zolpidem 5 mg/day. On physical examination, the patient was dehydrated and pale. Other findings included regular heart rhythm, normal heart sounds, with no murmurs detected. Blood pressure was 110 x 60 mmHg, and heart rate was 67 bpm. Vesicular breath sounds were within the physiological range. Adventitious respiratory sounds were not detected. Respiratory rate was 14 irpm. Bowel sounds were observed, and the abdomen was painless. There were no signs of visceromegaly or peritoneal irritation.
INVESTIGATION AND PROGRESSION
Tests and results were as follows: K = 6.4 mmol/L (reference range, RR = 3.5—5.0 mmol/L); Na = 110 mmol/L (RR = 135-145 mmol/L); creatinine = 1.1 mg/dL (RR: up to 1.5 mg/dL); urea = 31 mg/dL (RR = up to 50 mg/dL); chest radiography: cardiomegaly; electrocardiogram: no ischemic changes; myocardial scintigraphy: normal.
Hyponatremia was present during the entire admission. The patient also developed superficial thrombophlebitis of the left upper limb and was started on oxacillin (2 mg IV every 4 hours). As urine culture revealed growth of Klebsiella pneumoniae, antibiogram-guided ciprofloxacin (400 mg every 12 hours) was initiated. Periorbital cellulitis and endophthalmitis were treated with intravenous vancomycin (1 g every 12 hours) and moxifloxacin eye drops. Presence of septic thrombophlebitis was suspected.
A chest computed tomography (CT) scan showed groundglass opacity nodules in the lung, a comminuted fracture of the sternum, and bilateral pleural effusion (Figure 1). A pelvic CT scan revealed psoitis and abscess in the right greater trochanter, confirming the suspicion of staphylococcal infection.
On the 30th day of hospitalization, purulent fluid was found in the manubrium, suggesting osteomyelitis. Urine culture revealed Staphylococcus aureus. The sternum was approached for drainage of fluid and biopsy, and vancomycin was maintained for 4 weeks and the pulmonary nodules disappeared. A pathology test revealed PC infiltration compatible with plasmacytoma/MM. Immunohistochemistry showed evidence of acute osteomyelitis (Figure 2). Serum protein electrophoresis revealed a polyclonal increase in gamma globulins (Figure 3). Serum and urine immunofixation was negative.
After hematologic evaluation, due to improvement of clinical symptoms, the patient was discharged on the 68th day of hospitalization and was referred to outpatient follow-up. After one week, she returned with tumor lysis syndrome requiring dialysis, leading to her death.
Differential diagnosis included the following:
Monoclonal gammopathy of undetermined significance;
Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia);
The case of a patient with SPB involving the sternum is reported here. The diagnosis of this disease requires the following: one single area of bone destruction by a PC clone, no evidence of neoplastic infiltration in the marrow nor of lesions in other bones, and absence of anemia, hypercalcemia, and renal failure caused by MM.13 According to the literature, about 50% of patients with SPB will develop MM during their lifetime.14 In the present case, a varied set of signs and symptoms led to a diagnosis of SPB affecting the sternum. Also relevant was a positive result for lambda light chain, which indicates the presence of immature tumors, which are more likely to progress to MM.14
Tumor lysis syndrome is characterized by acute cell lysis with release of intracellular material. It may be associated with chemotherapy and radiotherapy effects or develop spontaneously.15,16
Refractory hyponatremia was a milestone in the present case. Syndrome ofinappropriate antidiuretic hormone secretion (SIADH) has been found in 67-80% ofcases ofmalignant neoplasms; pseudohyponatremia with normal serum osmolality, which has been classically described in hyperproteinemias, is another option.17,18
Infections are among the most important causes of morbidity and mortality in PC disorders, resulting from immunodeficiency associated with the disease. The main causative agents are Staphilococcus aureus and gram-negative bacteria, although the incidence of fungal infection has increased.19
In older patients with diffuse musculoskeletal pain and hyponatremia, differential diagnosis should include plasmacytoma/MM, which requires assessment with serum protein electrophoresis and erythrocyte sedimentation rate.
CONFLICT OF INTERESTS
The authors declare no conflict of interests.
1. Knowling MA, Harwood AR, Bergsagel DE. Comparison of extramedullary plasmacytomas with solitary and multiple plasma cell tumors of bone. J Clin Oncol. 1983;1:255-62. https://doi.org/10.1200/Jœ.19220.127.116.11
2. Dimopoulos MA, Hamilos G. Solitary bone plasmacytoma and extramedullary plasmacytoma. Curr Treat Options Oncol. 2002;3:255-9. https://doi.org/10.1007/s11864-002-0015-2
3. Dores GM, Landgren O, McGlynn KA, Curtis RE, Linet MS, Devesa SS. Plasmacytoma of bone, extramedullary plasmacytoma, and multiple myeloma: incidence and survival in the United States, 1992-2004. Br J Haematol. 2009;144:86-94. https://doi.org/10.1111/j.1365-2141.2008.07421.x
4. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538-48. https://doi.org/10.1016/S1470-2045(14)70442-5
5. Soutar R, Lucraft H, Jackson G, Reece A, Bird J, Low E, Samson D, et al. Guidelines on the diagnosis and management of solitary plasmacytoma of bone and solitary extramedullary plasmacytoma. Br J Haematol. 2004;124:717-26. https://doi.org/10.1111/j.1365-2141.2004.04834.x
6. Grammatico S, Scalzulli E, Petrucci MT Solitary Plasmacytoma. Mediterr J Hematol Infect Dis. 2017 Aug 23;9(1):e2017052. DOI: 10.4084/ MJHID.2017.052
7. Dimopoulos MA, Moulopoulos LA, Maniatis A, Alexanian R. Solitary plasmacytoma of bone and asymptomatic multiple myeloma. Blood. 2000;96:2037-44.
8. Galieni P, Cavo M, Pulsoni A, Avvisati G, Bigazzi C, Neri S, et al. Clinical outcome of extramedullary plasmacytoma. Haematologica. 2000;85:47-51.
9. Kilciksiz S, Celik OK, Pak Y, Demiral AN, Pehlivan M, Orhan O, et al. Turkish Oncology Group-Sarcoma Working Party. Clinical and prognostic features of plasmacytomas: a multicenter study of Turkish Oncology Group-Sarcoma Working Party. Am J Hematol. 2008;83:702-7. https://doi.org/10.1002/ajh.21211
10. Jawad MU, Scully SP. Skeletal Plasmacytoma: progression of disease and impact of local treatment; an analysis of SEER database. J Hematol Oncol. 2009;2:41. https://doi.org/10.1186/1756-8722-2-41
11. Thumallapally N, Meshref A, Mousa M, Terjanian T. Solitary plasmacytoma: population-based analysis of survival trends and effect of various treatment modalities in the USA. BMC Cancer. 2017;17:13. https://doi.org/10.1186/s12885-016-3015-5
12. Chiari AP, Cunha UGV, Thomaz DP. Caso 2: Mieloma Múltiplo. In: Chiari AP, Cunha UGV, Thomaz DP, eds. Geriatria: Oncologia Casos Clínicos. Belo Horizonte: Coopmed; 2018. p. 24-9.
13. Cardoso I, Secioso P, Moreira M. Plasmocitoma solitário ósseo: relato de caso. Rev Bras Clin Med. 2010;8(2):183-6.
14. Dimopoulos MA, Moulopoulos LA, Maniatis A, Alexanian R. Solitary plasmacytoma of bone and asymptomatic multiple myeloma. Blood. 2000;96(6):2037-44.
15. Darmon M, Malak S, Guichard I, Schlemmer B. Síndrome de lise tumoral: uma revisão abrangente da literatura. Rev Bras Ter Intensiva. 2008;20(3):278-85.
16. Tallo FS, Vendrame LS, Lopes RD, Lopes AC. Síndrome da lise tumoral: uma revisão para o clínico. Rev Bras Clin Med. 2013;11(2):150-4.
17. Maruichi MD, Pai CYW, Amadei G, Lopes RN, Tieppo CA. Síndrome da secreção inapropriada do hormônio anti-diurético. Arq Med Hosp Fac Cienc Med Santa Casa São Paulo. 2012;57(1):41-5.
18. Rocha PN. Hiponatremia: conceitos básicos e abordagem prática. J Bras Nefrol. 2011;33(2):248-60.
19. Oliveira AL, Nucci M. Infecção em Mieloma Múltiplo. Rev Bras Hematol Hemoter. 2007;29(1):77-85. http://dx.doi.org/10.1590/S1516-84842007000100015
November 6 2017.
Accepted em February 1 2018.