Metastatic Lobular Carcinoma of the Breast Presenting as a Frontal Scalp Mass and

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1 Metastatic Lobular Carcinoma of the Breast Presenting as a Frontal Scalp Mass and Masquerading as Lymphoma: A Potential Pitfall in Aspiration Cytology Lauren Altman 1, Summer Student; Raptis George 2, M.D.; Hua Chen 1 *, M.D., Ph.D. 1 Department of Pathology, 2 Division of Hematology and Medical Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York Running Title: Metastatic Breast Carcinoma Mimicking Lymphoma. Manuscript type: IMAGES IN CYTOLOGY. Correspondence to: Hua Chen, M.D., Ph.D. Division of Cytopathology, Department of Pathology, The Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1194, New York, NY Phone: Fax: Keywords: Metastatic, Carcinoma of Breast, Non-Hodgkin Lymphoma. A 54-year old woman with a history of lobular carcinoma of breast presented with a soft tissue mass on her frontal/parietal scalp. A fine needle aspiration biopsy was taken of the mass under Ultrasound guidance. Diff-Quick and Papanicolaou-stained smeared slides were prepared and examined. The aspirate was hypercellular and consisted of monotonous population of

2 dispersed neoplastic cells with small, uniform, bland looking, mostly stripped and round nuclei, some formed indistinct single cell file arrangement (Fig 1A). In addition, abundant pale-blue cytoplasmic fragments mimicking lymphglandular bodies were also noted in the background (Fig 1A insert). At high power view, the neoplastic cells were characterized by mild to moderate nuclear enlargement, small nucleoli, moderate nuclear membrane irregularity and scant cytoplasm (Fig 1A insert and Fig 1B). Cohesive cellular clusters, well-formed glandular acini, and intracytoplasmic lumens were not observed. During the initial on-site assessment, this lesion was misinterpreted as non-hodgkin lymphoma of small cell type. As a result of the patient s past history of lobular carcinoma of the breast, a metastasis could not be ruled out. An additional pass was performed and the specimen was submitted for flow cytometry analysis and preparation of a cell block. The cell block demonstrated mostly small blue neoplastic cells, some with vacuolated cytoplasm (Fig 1C). Indistinct single cell filing was also noted. Immunocytochemical stains were performed, and the neoplastic cells were diffuse and strongly positive for Estrogen receptor and Progesterone receptor, consistent with metastatic adenocarcinoma of the breast origin (Fig 1D). The neoplastic cells were negative for LCA/CD26. The flow cytometry indicated that the neoplastic cells were completely negative for lymphoid markers. Breast cancer is one of the most common cancers among US women. Lobular carcinoma is a variant of breast cancers arising in the milk-producing lobules of the breast. For year old women, about 6.5% of all breast carcinomas are lobular, according to a study of patients from Invasive lobular carcinoma breaks out of the lobules in single file pattern, invading the surrounding tissue in a web-like manner 2. 30% of all breast cancers will develop into metastatic breast cancer, and the main sites of metastasis are the lungs, liver, and bones 3. Non-Hodgkin Lymphoma is far more common than Hodgkin s disease; about 88% of all

3 lymphoma cases are non-hodgkin 4. Non-Hodgkin Lymphoma can be classified into B- and T- cell types, with B-cell neoplasms making up about 90% of all cases 5. Cytomorphologically, lobular breast carcinoma is often characterized by small to mid-size cells in single file arrangements. The cells take on a signet ring appearance or intracytoplasmic lumen as a result of a large cytoplasmic vacuole 5. Non-Hodgkin Lymphoma of small cells presents as monomorphous small to intermediated sized lymphocytes with fine or clumping chromatin, smooth or irregular nuclear membrane, inconspicuous nucleoli, scant cytoplasm 5. Lymphglandular bodies are commonly seen in the background. While cytomorphologies of lobular breast carcinoma and non-hodgkin lymphoma of small cells have little in common, they can occasionally mimic each other and can represent diagnostic pitfalls in fine needle aspiration biopsy. A similar case was reported in which a patient was originally diagnosed with malignant lymphoma because of high nuclear to cytoplasmic ratio, nuclear uniformity, and the single file and discohesive pattern of infiltration. However, the results of an Alcian blue/periodic acid- Schiff stain and immunohistochemical stains including cytokeratin CAM5.2 and estrogen receptor highly suggested lobular carcinoma of the breast 6. Although the initial onsite diagnosis is suspicious for lymphoma, second pass dedicated for flow analysis and cell block should be taken to avoid repeating the biopsy. This is important because it is very easy to mistake the morphologies and misdiagnose a patient with lymphoma. Cell block and flow cytometry are crucial in cases like this. Immunocytochemical staining is recommended if there is any uncertainty with the FNA smear, especially if the patient is considered to be at high risk for lobular breast carcinoma metastasis.

4 A: DQ 40x Insert: DQ 100x B: Pap C: Cell Block D: Immunostain Estrogen Receptor Figure 1. A: Monomorphous discohesive neoplastic cells with small, round nuclei and scant cytoplasm mimicking non-hodgkin lymphoma (Diff-Quick stain, X40). A (insert): Single file cell pattern characteristic of lobular breast carcinoma and cytoplasmic fragments mimicking lymphoglandular bodies in the background (Diff-Quick stain, X100). B: Loosely cohesive clusters of neoplastic cells with smooth chromatin and scant cytoplasm (Papanicolaou stain, X100). C: Loosely cohesive neoplastic cells with smooth chromatin and scant cytoplasm morphologically similar to non-hodgkin lymphoma (Cell Block, X100). D: Neoplastic cells showed strong and diffuse positive stains for Estrogen receptors. (Immunostain for Estrogen receptor, X100). 1. Li CI, Anderson BO, Porter P, Holt SK, Daling JR, Moe RE Changing incidence rate of invasive lobular breast carcinoma among older women. Cancer 88(11): Mann RM, Hoogeveen YL, Blickman JG, Boetes C MRI compared to conventional diagnostic work up in the detection and evaluation of invasive lobular carcinoma of the breast: a review of existing literature. Breast Cancer Res Treat 107(1): Patel JK, Didolkar MS, Pickren JW, Moore RH Metastatic pattern of malignant melanoma. A study of 216 autopsy cases. Am J Surg 135(6):

5 Cancer Facts & Figures Atlanta, GA: American Cancer Society. 5. Edmund S Cibas M, Barbara S Ducatman, MD Cytology: Diagnostic Principles and Clinical Correlates. Philadelphia, PA: Saunders Elsevier. 6. Wolstencroft SJ, Hodder SC, Askill CF, Sugar AW, Jones EW, Griffiths AP Orbital metastasis due to interval lobular carcinoma of the breast: a potential mimic of lymphoma. Arch Ophthalmol 117(10):

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