MedPix Medical Image Database COW - Case of the Week Case Contributor: Gregory S Brown Affiliation: Uniformed Services University

MedPix No: History Pt Demographics: Age = 46 y.o. Gender = woman 46 year-old woman with history of sarcoidosis, anemia, hypertension, and carpal tunnel syndrome with complaint of intermittent bilateral conjunctival inflammation and hemorrhage for one year. She was initially seen by opthalmology who diagnosed and treated her for conjunctivitis associated with bilateral lacrimal gland enlargement demonstrated on numerous CT studies of the orbits. She was diagnosed with sarcoidosis thirteen years prior via bronchoscopy and maintains that she has remained asymptomatic. She also has bilateral upper extremity paresthesias that are diffuse but most notable in the ulnar nerve distribution of both the right and left hands and she has been diagnosed with bilateral carpal tunnel syndrome in the past year. She presents with no other complaints and review of systems is negative for constitutional, cardiopulmonary, gastrointestinal, genitourinary, or musculoskeletal complaints. Her most recent head CT was obtained during evaluation of URI symptoms and pain over the right maxillary sinus, for which she was diagnosed with sinusitis. Downloaded by (-1)

MedPix No: EXAM & LABS Physical exam: notable only for bilateral conjunctivitis and conjunctival hemorrhage and swelling Lab:No abnormal findings

Multiple Myeloma Bilateral Lacrimal gland enlargement Downloaded by (-1)

Multiple Myeloma 5-9mm diameter lucencies posterior to the vertex Downloaded by (-1)

Multiple Myeloma Bony lucencies in the radial tuberosity and proximal humerus. Downloaded by (-1)

Multiple Myeloma round, singular bony lucency of the lateral left clavicle. Downloaded by (-1)

Multiple Myeloma 5-9mm diameter lucencies posterior to the vertex Downloaded by (-1)

Multiple Myeloma Round lucency in spinous process of C3 and vertebral body of C6. Downloaded by (-1)

FINDINGS Head CT: Bilateral Lacrimal gland enlargement with homogenous tissue attenuation. Multiple lucenies of the skull bilaterally, particularly posterior to the vertex ranging 5-9 mm in size. Diffuse soft tissue attenuation noted in right maxillary sinus consistent with sinusitis. Skeletal Survey: Left upper extremity-single round, punched-out appearing lucencies in the region of the radial tuberosity and proximal humerus; PA-chest-single, round, punched out appearing lucency in the lateral left clavicle; Skull-numerous, round, punched-out appearing lucencies over the parietal and frontal bones.

DIFFERENTIAL DIAGNOSIS What is your Differential Diagnosis? Multiple Myeloma - Osteolytic Metastatic Carcinoma - Hyperparathyroidism -

Diagnosis: Multiple Myeloma and secondary amyloidosis and history of sarcoidosis Dx Confirmed by: Lacrimal gland biopsy demonstrating diffuse amyloid deposition. Serology demonstrates monoclonal gammopathy. Bone marrow biopsy pending pathologic analysis.

DISCUSSION This is a case of a 46 year-old black female with a history of sarcoidosis diagnosed at age 32 years, and bilateral carpal tunnel syndrome diagnosed within the past year now presenting with mulitple myeloma. Multiple myeloma (MM) is a monoclonal B-cell malignancy consisting of terminally differentiated plasma cells. In the United States, the incidence of disease is 3-4 newly diagnosed cases per 100,000 population per year, and represents 1% of all malignancies. Demographically, patients are commonly African-American, with males slightly outnumbering females by Patients are typically elderly with a median age of 65 years at diagnosis, although cases in much younger patients have been reported. - - The patient*s presentation for MM is unusual given her relatively young age (46 years), lack of physical findings and history (i.e. fatigue, bone, recurrent infections), and laboratory abnormalities (i.e. hypercalcemia, elevated creatinine, elevated total protein) suggestive of MM. The bilateral lacrimal gland amyloidosis is a unusual initial presentation for MM. By comparison, lacrimal gland involvement in sarcoidosis is more common affecting 55-61% of patients at sometime during their disease course with similar findings on CT imaging. Therefore, her management was based on the conclusion her presentation was a manifestation of her sarcoidosis and not MM. The lack of response to therapy for the lacrimal gland enlargement ultimately prompted a biopsy of the gland six months from the time she sought medical attention, and one year since she reported initially having symptoms. - - The lacrimal gland biopsy showed an inflamatory cell infiltrate, with nodules of pauci- cellular, eosinophillic staining material exhibiting apple-green birefringence on Congo Red staining. This is consistent with amyloidosis of the lacrimal gland. The lack of evidence of granulomatous disease present in the biopsy specimen strongly suggests that sarcoidosis is not the etiology of her lacrimal gland enlargement. - - Based on the above findings, the patient received further laboratory and radiological investigations for the diagnosis of MM. The diagnosis of MM is based on the demonstration of three components: 1) Serum or urine monoclonal protein identified by a characteristic monoclonal M protein spike on electrophoresis of urine and blood specimens; 2) >10% abnormal plasma cells on bone marrow biopsy; and 3) end-organ damage in the form of hypercalcemia, renal insufficiency, sequelae of amyloid deposition, and/or bone abnormalities on imaging. Most patients will demonstrate symptomatic sequelae of of end- organ damage. However, nearly 25% of patients with MM are discovered through incidental findings on laboratory studies and imaging. Indeed, radiographs provided the only significant finding suggestive of MM via a head CT that was obtained for the evaluation of URI symptoms of sinusitis in an emergency department several months prior to the lacrimal gland biopsy. - - The characteristic radiological feature of MM is the presence of a single osteolytic lucency (plasmacytoma), or, as in this patient*s case, multiple discrete osteolytic lucencies (myelomatous) that are subcortical and found predominantly in the axial and proximal appendicular skeleton. Lesions may also coalesce or take the form of diffuse osteopenia. Sclerosing myeloma has also been described, although it is rare. The osteolysis of MM is mediated by the secretion of chemokine factors by the malignant plasma cells that stimulate osteoclast proliferation, chemotaxis, maturation, and activity. - - Plain film radiograph skeletal survey is the preferred diagnostic modality for the detection of bony involvement in MM. Nearly 50% of the density of bone must be affected before the *punched-out* lesions are apparent, however, the presence of bone lesions is confirmed in 60-80% of all patients initially surveyed for MM with radiograph. Other useful imaging studies include MRI, which may be used for the precise determination of lesion size and location for bone marrow biopsy, targeted radiotherapy, and for characterization of the extent of disease. Imaging via CT is adjunctive to MRI for guided biopsy of lesions. Recently, PET scanning has shown promise for monitoring disease recurrence by detection of lesions not readily seen on conventional radiograph. - - Due to the osteolytic nature of MM, nuclear imaging via technec tium-99m (Tc-99m) bone scanning has no role in diagnosis or monitoring. The sensitivity of Tc-99m scanning is dependent on osteoblastic activity, and therefore, underestimates the extent of disease. Uptake of Tc-99m into radiographically abnormal regions is only 44% compared to conventional plain film. This uptake is secondary to osteoblastic activity from pathological fracture, calcification within a plasmacytoma, or amyloidosis in association with tumor. - - The presence of osteolytic lesions is not pathognomonic of MM, as such findings may be present in a variety of conditions including other osteolytic metastases and occasionally lymphoma) and hyperparathyroidism Furthermore, bilateral lacrimal gland enlargement with homogenous soft tissue attenuation seen on CT is more suggestive of lacrimal gland sarcoidosis than other etiologies. Neoplastic and infectious processes tend to present with discrete lesions within the lacrimal gland and/or are likely unilateral. The chronicity of symptoms also would argue against a bilateral infection, as such a condition would be likely self-limiting. The apparent overlap of expected findings in sarcoidosis versus that of MM likely contributed to the lag between initial presentation and diagnosis.