A 64-year-old man comes to the office due to 3 months of constant, dull, low back pain that is worse with movement. The patient has also had intermittent episodes of difficult urination over the last year. He has no other medical conditions and takes no medications. The patient smoked a pack of cigarettes daily for 15 years but quit 10 years ago. Vital signs are within normal limits. On physical examination, the lungs are clear and heart sounds are normal. The abdomen is soft and nontender with no hepatosplenomegaly. Digital rectal examination shows a diffusely enlarged prostate with no nodules. Laboratory testing reveals a serum creatinine level of 1.9 mg/dL. Urine dipstick testing is within normal limits, but 24-hour urinary protein excretion is elevated. Urine microscopy shows waxy, laminated casts. Imaging of the spine demonstrates diffuse osteopenia and multiple irregular, radiolucent lesions in the thoracic and lumbar vertebrae. Which of the following histopathologic findings is most likely associated with the development of this patient's bone lesions?

Question

A 64-year-old man comes to the office due to 3 months of constant, dull, low back pain that is worse with movement.  The patient has also had intermittent episodes of difficult urination over the last year.  He has no other medical conditions and takes no medications.  The patient smoked a pack of cigarettes daily for 15 years but quit 10 years ago.  Vital signs are within normal limits.  On physical examination, the lungs are clear and heart sounds are normal.  The abdomen is soft and nontender with no hepatosplenomegaly.  Digital rectal examination shows a diffusely enlarged prostate with no nodules.  Laboratory testing reveals a serum creatinine level of 1.9 mg/dL.  Urine dipstick testing is within normal limits, but 24-hour urinary protein excretion is elevated.  Urine microscopy shows waxy, laminated casts.  Imaging of the spine demonstrates diffuse osteopenia and multiple irregular, radiolucent lesions in the thoracic and lumbar vertebrae.  Which of the following histopathologic findings is most likely associated with the development of this patient's bone lesions?

Quizplus · Accepted Answer

11ec160b_398a_9f4e_9249_c74029eb5fd9_MD0001_00 This older patient with back pain has several irregularly-shaped vertebral lesions, raising strong suspicion for metastatic disease. Differentiation of the underlying tumor is often assisted by whether the lesion is sclerotic (osteoblastic) or radiolucent (osteolytic). Multiple myeloma, a clonal plasma cell malignancy, is one of the most common causes of radiolucent bone lesions in adults; the tumor multiplies in the bone marrow and generates osteolytic cytokines, causing bone pain, bone destruction, pathologic fractures, and hypercalcemia. Myeloma cells also produce excessive monoclonal immunoglobulin (paraprotein) that can clog the renal tubules and subsequently cause light-chain cast nephropathy. This is typically characterized by mild renal insufficiency, normal urine dipstick for protein (detects albumin only), elevated 24-hour urine protein (can detect light-chain proteins), and waxy, laminated casts. Excessive light chains can also form fibrils and deposit in tissues, leading to amyloid light-chain amyloidosis. Monoclonal immunoglobulins are identified by urine or serum protein electrophoresis (M-spike). The diagnosis of myeloma is confirmed by bone marrow aspirate or biopsy, which will demonstrate ≥10% clonal plasma cells. Plasma cells are identified based upon "clock-face" chromatin, abundant basophilic cytoplasm, and prominent perinuclear clear areas (Golgi apparatus). (Choice A) Papillary thyroid cancer is characterized by branching papillae lined by cuboidal cells with overlying nuclei (often with calcified psammoma bodies). Most cases progress slowly and present with a thyroid mass that may invade adjacent structures; bone lesions are relatively uncommon. (Choice B) Prostate adenocarcinoma is a glandular tumor that often spreads to the bones. However, it produces sclerotic (osteoblastic) bone lesions, not radiolucent bone lesions. Furthermore, prostate cancer does not generally impinge on the urethra (urinary symptoms uncommon) and is usually associated with a nodule on prostate examination; this patient's intermittent difficulty urinating and diffusely enlarged prostate with no nodules likely indicate benign prostatic hyperplasia. (Choices C and E) Squamous cell lung cancer is associated with large, malignant cells containing keratin with intercellular bridges. Renal cell carcinoma is associated with sheets of round or polygonal cells with abundant clear cytoplasm. Although both tumors commonly form osteolytic lesions in the spine, neither regularly cause renal insufficiency, elevated urine protein, and waxy urinary casts. Educational objective: Multiple myeloma is a plasma cell malignancy that replicates in the bone marrow and causes osteolytic bone lesions, bone destruction, hypercalcemia, and pathologic fractures. Histopathology will show replacement of the normal bone marrow with plasma cells and plasmablasts. __________ References: Bone disease in multiple myeloma: pathophysiology and management. (http://www.ncbi.nlm.nih.gov/pubmed/25187738)

A 64-Year-Old Man Comes to the Office Due to 3