A 72-Year-Old Woman With Back Pain and Hypercalcemia

Tarah Ballinger, MD; Kathy D. Miller, MD


July 27, 2016


A liver biopsy was performed, which showed diffuse proliferation of atypical cells (Figure 3). Immunostaining was positive for CD10, CD20, BCL-6, and MUM-1, and negative for HER2, S100, CD30, and cytokeratin.

Figure 3.

The imaging performed in this patient showed multiple enlarged lymph nodes as well as lesions in the bones and liver, which were initially concerning for new metastases of her prior breast cancer. However, morphologic findings on biopsy showed large, atypical B cells destroying the normal lymph node architecture. The tumor cells were large, with prominent nucleoli and basophilic cytoplasm. This could be consistent with multiple possible cancers, and the differential diagnosis was narrowed using further information provided by immunostaining.

The cells are positive for the B-cell markers CD10 and CD20, as well as the B-cell lymphoma proteins BCL-6 and MUM-1. This morphology and immunophenotype is consistent with a diagnosis of diffuse large B-cell lymphoma (DLBCL). Her hypercalcemia was probably due to production of parathyroid-related protein and 1,25-dihydroxyvitamin D (calcitriol) by the lymphoma cells.[1]

This case illustrates the importance of biopsy for first recurrence of breast cancer after primary treatment. The National Comprehensive Cancer Network (NCCN) guidelines recommend that the first recurrence of breast cancer or metastatic disease be biopsied, to accurately determine the diagnosis and tumor histology. In addition, if the biopsy is consistent with recurrent breast cancer, this also allows redetermination of ER, PR, and HER2 status, which can change between primary and metastatic breast cancers.

Numerous retrospective studies have reported various ranges of receptor status changes between primary tumors and metastatic or local recurrences: as much as 40% for ER receptor status and as much as 14% for HER2 receptor status, with one study reporting HER2 discordance of 27%.[2,3,4,5,6,7] For hormone receptors, it is more common to lose receptor positivity than to gain it. Literature is conflicting on whether it is more common to gain HER2 expression or to lose it; however, loss of HER2 positivity in tumors previously exposed to chemotherapy has been documented.[3,8] Many reasons have been proposed for these changes. The biology of the tumor may change; for example, giving hormone therapy to an ER-positive tumor could select for any ER-negative tumor cells to grow and metastasize.

Alternatively, errors in pathologic determination of receptor status or heterogeneity within the tumor may occur, meaning that different parts of the tumor have varying expression of a receptor.[9] Therefore, owing to the possibility for sampling error, taking the patient's clinical course into consideration is important when interpreting biopsy results. For example, in patients who have an indolent clinical course consistent with ER-positive breast cancer and whose primary cancer was ER-positive, testing a course of antiestrogen therapy is reasonable, even if the metastatic disease is ER-negative.


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