Xanthogranulomatous Breast Mass: An Unusual Presentation

Xanthogranulomatous inflammatory reactions are benign inflammatory processes characterized by aggregating lipid-laden foamy macrophages. Although cases have been reported in different organ systems, these rare reactions predominantly occur in the kidney and gallbladder. We present a 92-year-old female who noticed a palpable, tender mass in the lower inner quadrant of her right breast with no skin changes. She was referred to surgery by her primary care physician on suspicion of malignancy and further evaluation. Ultrasound-guided biopsy, ordered by the primary care provider, revealed a suspicious high-grade malignant neoplasm of uncertain origin. Pathological findings include the presence of an unusual population of malignant epithelioid cells with a striking xanthogranulomatous reaction, along with numerous Touton-like histiocytes. These findings are comparable in morphology to a recently reported xanthogranulomatous epithelial tumor. Given the lack of history of breast carcinoma in this patient as well as the lack of immunohistochemical studies suggesting breast carcinoma, treatment involved continuing standard of care for an unusual high-grade sarcoma via lumpectomy. A positron emission tomography (PET) scan was ordered to ensure there was no spread or alternate origins of the cancer tissue. This case report brings to light the findings of a probable xanthogranulomatous tumor in breast tissue, an exceptionally rare phenomenon in breast cancer, especially in the elderly population. Due to the rarity of xanthogranulomatous tumors in the breast, prognosis and standardized treatment have yet to be established.


Introduction
Breast cancer is one of the most common cancers among women in the United States (US) [1]. The most common categories of breast cancer are infiltrating ductal carcinoma and lobular carcinoma. In this case, an unusual breast tumor was discovered in an elderly patient, with distinctive histologic features that have previously not been documented. These include weakly keratin-positive epithelial cells with malignant cytologic features. This tumor also had characteristic features of a xanthogranulomatous reaction [2] and was immunohistochemically negative for several key markers mentioned in the discussion.
Xanthogranulomatous inflammatory reactions are benign inflammatory processes characterized by aggregating lipid-laden foamy macrophages. These reactions predominantly occur in the kidney and gallbladder [3,4] and are generally triggered by abscesses, necrosis, and hemorrhage. They are characterized by eosinophilic, granular, periodic acid-Schiff (PAS)-positive histiocytes in initial stages, followed by foamy macrophages, activated plasma cells, suppurative foci, and hemorrhages [2]. Eventually, these lesions and neoplasms become fibrotic. Recently, epithelial tumors have been identified in soft tissue and bone in six cases that presented with features of xanthogranulomatous inflammation. These cases involved young patients, and the tumors behaved like low-grade neoplasms [5].
We present a case report of a patient with a right breast mass that was inconsistent with previously documented histological and pathological features of breast cancer. Rather, it had characteristics consistent with xanthogranulomatous epithelial tumors. Because of the tumor's close resemblance to carcinoma with tumor cells, comprised of abundant cytoplasm and prominent nucleoli, it introduced challenges with regards to the treatment approach. Due to lack of tumor extension into surrounding tissues, and negative immunohistochemical studies, treatment was continued under the notion that this tumor was an unusual high-grade sarcoma [6].

Case Presentation
An elderly 92-year-old female noticed a palpable mass in the lower inner quadrant of her right breast for several months. The patient reported occasional palpable tenderness but no skin changes, nipple retraction, or discharge. She denied any family history of breast cancer.
A mammogram was performed and demonstrated a suspicious right breast mass (Figure 1). It was followed up with ultrasound-guided core-needle breast biopsy, which further showed a large, lobulated mass corresponding to the mammographic findings suspicious for a malignant neoplasm, Breast Imaging-Reporting and Data System (BI-RADS) category 4 [7].

Discussion
This inflammatory process of a xanthogranulomatous reaction is a rare pathological finding; however, it has been described in many organ systems including the gallbladder, kidneys, and ovaries. This reaction causes a diffusely destructive process that can be compared to chronic cholecystitis in the gallbladder but mimicking gallbladder carcinoma [8]. Xanthogranulomatous pyelonephritis, also diagnosed by histology, has also shown similar features to that of renal cell carcinoma [9]. Breast involvement is limited to a few cases of mastitis and can be described as a solid lump masquerading as a malignancy [10].
Pathological analysis of the tumor, in this case, displayed an unusual population of malignant-appearing epithelioid cells with a striking xanthogranulomatous reaction including aggregating lipid-laden foamy histiocytes ( Figure 2) and numerous Touton-like histiocytes (Figure 3) surrounded by a fibrous capsule (Figure 4). Another striking feature of xanthogranulomatous inflammation included a lipid-laden necrotic reaction ( Figure 5). These features, while rare, were comparable in morphology to a recently reported xanthogranulomatous epithelial tumor. Additionally, the tumors seemed to behave as lowgrade neoplasms in a younger population (16-62 years) [5].    By immunohistochemistry, many of the malignant-appearing epithelioid cells are weakly positive for keratins with the AE1/AE3 antibody and epithelial membrane antigen. Signal transducer and activator of transcription 6 (STAT6), transducin-like enhancer of split 1 (TLE1), high molecular weight keratin, CAM 5.2, S100 protein, OSCAR keratin, CD3, CD20, CD30, CD45, CD68, smooth muscle actin, and desmin are negative in these cells. Very focal reactivity was shown to estrogen receptors (ER) with negative results for progesterone receptors (PR), pankeratin, melanoma antigen recognized by T cells (Mart-1), and Human Melanoma Black (HMB-45) [11]. CD163 is positive in background histiocytes. Integrase interactor 1 (INI1) and Brahma-related gene-1 (BRG1) expression are retained. Keratin 7 is negative. While this tumor bears striking resemblance to the xanthogranulomatous epithelial tumor, it is difficult to rule out the possibility of an exceptionally unusual carcinoma. The unusual histological findings, especially in the breast, present a challenge in determining the true etiology of this inflammatory process and whether it is a true xanthogranulomatous epithelial tumor or a unique incidental inflammatory finding. Given the lack of history of breast carcinoma in this patient as well as the lack of immunohistochemical studies suggesting breast carcinoma, treatment involved continuing standard care for an unusual high-grade sarcoma via lumpectomy [6]. Wide clear margins were obtained and the patient refused further care probably due to her advanced age and unwillingness to undergo further treatment such as chemotherapy or radiation to prevent recurrence but continued to follow with oncology.