A rare finding of brown fat in bone marrow as a mimic for metastatic disease
Authors: Katelyn Dannheim, Parul Bhargava
Journal: American Journal of Hematology (2016)

A 54-year-old woman presented with newly elevated CA 27.29, a tumor marker for breast cancer, which rose from 32 U/mL (9 months prior) to 61 U/mL (reference range 0–39 U/mL) and was verified on repeat testing. She had a significant history of bilateral breast carcinoma, both right-sided ductal carcinoma and left-sided lobular carcinoma, status post bilateral mastectomies five years prior. Her surgical history also included a remote resection for Stage I renal cell carcinoma, and resections for multiple parathyroid adenomas. Additionally, her medical history included hypertension, Hashimoto's thyroiditis, osteopenia secondary to hyperparathyroidism, and prior lithium toxicity resulting in Stage III/IV chronic kidney disease. Persistent elevation in the tumor marker prompted a PET-CT scan, which revealed a sclerotic lesion within the right sacral ala (Image 1A). A CT-guided biopsy was performed to rule-out metastatic disease. Histopathologic examination unexpectedly revealed a focus of brown adipose tissue. No carcinoma was seen. One-third of the core length displayed trilineage hematopoietic marrow with an age-appropriate cellularity of 30–40% (Image 1B, left half). The remaining core length was hypocellular, and largely devoid of hematopoietic precursors, with an abrupt transition to interstitial brown fat cells present singly and with focal clustering (Image 1B, right half & inset). There appeared to be prominent background vascularity, focal bony remodeling, and some stromal damage. Sections of the marrow clot showed hematopoietic elements with occasional scattered brown fat cells. A: CT scan showing sclerotic lesion of the right sacral ala. B: Bone biopsy, H&E: Trilineage hematopoiesis with abrupt transition (marked by black arrows) to brown fat. Inset (top right) shows high power image of adipocytes with multiple small cytoplasmic vacuoles (brown adipocytes). C,D: Immunohistochemical stains show that these cells are immunoreactive for S100 (C) and negative for macrophage marker CD68 (D), consistent with brown adipocytes. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] Immunohistochemical stains were performed to show that these cells were immunoreactive for S100 (Image 1C) and negative for macrophage marker CD68 (Image 1D), consistent with brown adipocytes. CD20 and CD3 stained a subset of background lymphocytes; no lymphoid aggregates were appreciated. Mast cell tryptase highlighted few scattered mast cells, with no clustering. CD117 also highlighted mast cells, as well as normal myeloid elements. Cytokeratin was negative. Brown fat is a form of fetal/neonatal adipose tissue involved in thermoregulation. It gradually disappears with age, but can persist in adults, primarily in the interscapular region, axilla, chest wall, mediastinum, and retroperitoneum. These are sites where hibernomas normally arise. Hibernomas are benign tumors of brown fat, equivalent to lipomas in white fat. While white fat is a normal component of bone marrow, the finding of brown adipocytes within bone marrow is extremely rare. Only a handful of cases with intraosseous brown fat have been reported in the literature 1-4. These few cases describe both men and women, aged 48–85, who underwent radiologic studies for staging of malignancy or work-up of back or lower-limb pain. Imaging showed intraosseous lesions such as the one described above, and resulting concern for metastatic disease or myeloproliferative disorders led to biopsy. Subsequent histopathologic examination showed collections of adipocytes with characteristic multivacuolation (brown fat cells) or a hibernoma. While this type of lesion seems benign in nature, its non-specific imaging features require biopsy for definitive diagnosis. It is therefore important to recognize it histologically as well as radiologically, as failure to do so may also lead to unnecessary repeat biopsies, imaging, and patient anxiety.