Hematologic Malignancies of the Breast: A Contemporary Series Investigating Incidence, Presentation, Accuracy of Diagnosis on Core Needle Biopsy, and Hormone Receptor Expression

Abstract

Background: Distinguishing breast hematologic malignancies in core needle biopsies from other entities can be challenging. Misclassification as a breast carcinoma could result in inappropriate treatment. The aim of this study was to characterize the types, incidence, and helpful diagnostic features of hematologic malignancies of the breast.

Design: All hematologic malignancies of the breast diagnosed at our institution from 2004 to 2017 were identified. Clinical notes, imaging, and slides were reviewed. Immunohistochemical analysis of estrogen receptor α (ERα), estrogen receptor β (ERβ), and androgen receptor (AR) was performed when tissue was available.

Results: In all, 43 hematologic malignancies from biopsies of 37 women and 6 men were identified. Core needle biopsies (35 or 81%) were more common than excisions (8 or 19%). For 14 patients (40%), the core biopsy was the first diagnosis of a hematologic malignancy. Diagnoses included 37 lymphomas (7 primary), 4 leukemias, and 2 myelomas. There was 1 misdiagnosis of carcinoma. Low positivity for hormone receptors was observed in a minority of lymphomas. A definitive diagnosis of hematologic malignancy was made in 31 (89%) of the core needle biopsies. Only 3 patients undergoing core biopsy required excision for diagnosis.

Conclusions: Most of the hematologic malignancies of the breast are currently diagnosed on core needle biopsy and 40% of patients do not have a prior history. To avoid errors, pathologists need to be aware of diagnostic features and morphologic mimics. A hematologic malignancy should be considered if tumor cells are discohesive, carcinoma in situ is absent, and hormone expression is low or absent.

Keywords: breast hematologic malignancies; breast lymphoma.

Figure 1.

Diffuse large B-cell lymphoma (DLBCL). (A) DLBCL typically involved most of the core needle biopsy (20×, H&E). Breast epithelium was often absent or only present focally at the periphery of the biopsy. (B) The tumor cells had pleomorphic nuclei and numerous mitotic figures were present (400×, H&E). (C) This DLBCL was initially mistaken for an invasive carcinoma (40×, H&E). Unlike other cases, this lymphoma invaded around breast epithelium and into adipose tissue, rather than forming solid areas of tumor cells. (D) This DLBCL shows strong diffuse nuclear immunoreactivity for p63 and does not express keratin (100×, immunohistochemical study for p63 and keratin AE1/AE3). H&E indicates hematoxylin and eosin stain.

Figure 2.

Marginal zone lymphoma. (A) Most of the core is involved by a diffuse proliferation of small lymphocytes. Occasional residual follicles are present. Scattered plasma cells and a minor population of larger cells were typically present. (B) Breast epithelium was either absent or only focally present. In 2 cases, lymphoepithelial lesions were present but were focal and inconspicuous. (C) In 1 case, scattered larger lymphocytes were present. The findings were not considered sufficient for a diagnosis of high-grade lymphoma. (D) Plasmacytoid features in lymphomas can mimic invasive lobular carcinoma. In 1 case, keratin was performed to exclude carcinoma.

Figure 3.

Follicular lymphoma. (A) This follicular lymphoma surrounds breast epithelium but also extensively involves interlobular stroma (40×, H&E). Neoplastic follicles are present. (B) This intramammary lymph node involved by follicular lymphoma shows numerous closely spaced follicles (20×, H&E). (C) A neoplastic follicle of follicular lymphoma lacks tingible body macrophages and mitoses are absent (100×, H&E). (D) This reactive lymph node shows enlarged normal germinal centers (20×, H&E). H&E indicates hematoxylin and eosin stain.

Figure 4.

(A) Small-cell lymphocytic lymphoma involving the breast surrounds epithelium but also extends into the interlobular stroma (20×, H&E). The epithelium is not atrophic and the stroma appears normal. (B) In lymphocytic mastopathy, clouds of lymphocytes surround atrophic lobules and blood vessels (20×, H&E). The stroma is densely hyalinized. (C) Lymphocytes can involve epithelium in benign lesions, such as in this case of lymphocytic mastopathy. Therefore, this finding is not specific for lymphomas. (D) T-cell lymphocytic lobulitis is seen as lymphocytes surrounding lobules (20×, H&E). Blood vessels are not involved. The stroma and non-involved lobules appear normal. H&E indicates hematoxylin and eosin stain.

Figure 5.

(A) This case of acute myelogenous leukemia resembles invasive lobular carcinoma due to the rounded discohesive cells infiltrating as linear arrays and solid nests (100×, H&E). The tumor cells encircle a duct. Although this pattern is also seen in lobular carcinoma, the tumor cells usually form wider circles in stroma and do not abut the basement membrane. (B) This case of Hairy cell leukemia is present as nests and single cells (100×, H&E). The monomorphic round nuclei are surrounded by a moderate amount of pale cytoplasm. (C) Myeloma involving the breast consisted of markedly atypical plasma cells with nuclear pleomorphism and numerous mitotic figures (100×, H&E). Extensive necrosis was present. (D) Amyloid can be detected on mammographic screening due to the formation of masses or calcifications (40×, H&E). A minority of patients with amyloid in the breast have myeloma. Although focal areas of lymphocytes are present, this patient did not have a monoclonal gammopathy. H&E indicates hematoxylin and eosin stain.