Case Presentation: A 43-year-old man with a history of chronic hepatitis B on antiviral therapy was admitted to a hospital medicine service with low back pain, weight loss, fevers, and fatigue over 2-3 months. Exam showed cervical lymphadenopathy (LAD), and initial labs were notable for a hemoglobin of 9.7g/dL, platelet count of 40×109/L, and rare circulating blasts. A recent outpatient MRI lumbar spine performed for work-up of low back pain showed heterogeneous diffuse T1 hypointense bone marrow, suggestive of malignancy. The patient had no family history of cancer. Brain, chest, and abdominopelvic imaging showed hepatosplenomegaly and diffuse marrow heterogeneity throughout the axial and appendicular skeleton without a primary tumor, concerning for a hematologic malignancy. A broad infectious workup was also performed given his history of hepatitis B and recent travel to the Philippines, which was negative. Bone marrow biopsy unexpectedly revealed estrogen receptor-weak positive (10%), progesterone receptor-negative, HER2-negative metastatic breast cancer. Cervical lymph node and liver biopsies to obtain additional tissue for molecular testing corroborated the diagnosis. Serologic markers of breast cancer (CA15-3, CA 27-29, CEA) were elevated, whereas markers of other cancers (AFP, PSA, HCG) were all normal. Oncology was consulted and the patient was started on capecitabine with outpatient oncology follow-up. MRI breast and whole-body PET CT did not identify a primary lesion.
Discussion: Hospitalists commonly care for patients with cytopenias requiring a malignancy evaluation. Our patient’s thrombocytopenia, anemia, and B symptoms without a radiographic culprit lesion initially raised highest suspicion for a hematologic malignancy, for which we pursued a bone marrow biopsy. Surprisingly, the results revealed metastatic breast cancer; breast cancer is rare in men, but metastatic breast cancer without a primary is an even rarer entity [1]. This case also highlights that solid tumors with significant marrow infiltration may present similarly to hematologic malignancies. As was the case for this patient, metastatic solid malignancies may rarely present without a primary tumor. Furthermore, immunophenotyping of the peripheral blasts suggested they were displaced by carcinoma (known as myelophthisis), rather than a manifestation of a hematologic malignancy. Cancer of unknown primary (CUP) is defined as the presence of metastatic cancer without an identified primary lesion at the time of diagnosis. Current diagnostic guidelines for CUP with bony involvement recommend pan-CT and biopsy of accessible lesions, with immunohistochemical testing for hormone receptors and HER2, as well as a breast MRI if there are concerns for breast cancer [2]. Treatment involves systemic therapy, which our patient has been undergoing in the outpatient setting [2].
Conclusions: New diagnoses of malignancy commonly occur on hospital medicine services when patients present with subacute symptoms or concerning lab abnormalities. While profound cytopenias and B symptoms raise suspicion for hematologic malignancies, metastatic solid cancers with significant marrow infiltration may present similarly. Rarely, workup may result in CUP. This case highlights the importance of imaging, serologic tumor markers, and histopathology to arrive at a diagnosis of metastatic breast cancer in a man.