Hunsaker et al" described Jansen YJ, Janssens P, Hoorens A, Schreuer MS, Seremet T, Wilgenhof S, et al.. Granulomatous nephritis and dermatitis in a patient with BRAF V600E mutant metastatic melanoma treated with dabrafenib and trametinib: Assan F, Schlemmer F, Assie J-B, Mahevas M, Sustronck P, Ortonne N, et al.. Atypical systemic sarcoid-like granulomatosis in two patients treated with BRAF and MEK inhibitors. Revista Espaola de Medicina Nuclear e Imagen Molecular. The malignancies occurred in <1% of the patients (94). Data extraction from the medical records included: medical history, medical images, and histological and pathological reports from breast tissue biopsies. 1. reported one case where the differential diagnosis between sarcoidosis and metastasis was made using whole body diffusion MRI (119). In another recent review of 115 cases, thyroid and breast cancers were the most frequently reported solid neoplasms (30). Among patients with breast cancer, the female predominance appears to be higher. Edited by: Mehdi Mirsaeidi, University of Miami, United States, Reviewed by: Gonalo Boleto, Hpitaux Universitaires Piti Salptrire, France; Mukunthan Murthi, John H. Stroger, Jr. Hospital of Cook County, United States; Viktor Korendovych, University Medical Center Gttingen, Germany, This article was submitted to Rheumatology, a section of the journal Frontiers in Medicine. Kirshy D, Gluck B, Brancaccio W. Sarcoidosis of the breast presenting as a spiculated lesion. first reported an increased risk of cancer in sarcoidosis patients ().Indeed, in this series, the risk of lymphoma was 11 times higher in the sarcoidosis group, compared to the . Histological features were not described in this article. Table 2 displays the findings for all of patients with both breast cancer and sarcoidosis. A careful and rigorous diagnosis process is required when encountering granulomatosis, on the one hand, because of the increased risk of neoplasia in sarcoidosis patients and, on the other hand, because of the sarcoidosis-like presentation of neoplasia. Crouser ED, Maier LA, Wilson KC, Bonham CA, Morgenthau AS, Patterson KC, et al.. ASCO Ann Meet Proc (post-meeting ed), J Clin Oncol. Accordingly, sarcoidosis can mimic breast cancer, making the differential diagnosis very difficult. Additionally, a comprehensive literature review which identified 104 patients diagnosed with breast cancer and sarcoidosis was carried out. Furthermore, sarcoid-like reaction in regional lymph nodes can conceal a metastasis and needs to be carefully evaluated [65]. Indeed, in two recent meta-analyses, the relative risk of developing cancer in patients with sarcoidosis was near 1.191.21 [with significant results in both studies (p < 0.05)] and the risk of developing hematological malignancies was even higher [RR = 1.92, 95% CI (1.412.62)] (27, 28). Diagnosis and Management of Sarcoidosis | AAFP Brandy-Garca AM, Cabezas-Rodriguez I, Caminal-Montero L, Suarez-Cuervo C, Redondo-Buil P. Sarcoidosis mimicking lytic osseous metastases. Staging breast cancer patients with sarcoidosis can be challenging as the differential diagnosis between sarcoidosis lesions and metastasis can be difficult by radiologic evaluations. Tomimaru Y, Higashiyama M, Okami J, Oda K, Takami K, Kodama K, et al.. Surgical results of lung cancer with sarcoid reaction in regional lymph nodes. An increased cancer risk in patients with sarcoidosis has been suggested, although results are conflicting in a number of case-control and cohort studies. When breast cancer preceded sarcoidosis, the average interval was 4 years and 8 months. The immunosuppressants can be linked to a theoretical increased risk of malignancy. For example, B-cell activating factor (BAFF) levels are elevated in patients with sarcoidosis and are correlated with ACE levels (99). Gansler TS, Wheeler JE. Increased risk of active tuberculosis after cancer diagnosis, Atypical mycobacterial infections in children with cancer. Chan W-L, Ramsay SC, Szeto ER, Freund J, Pohlen JM, Tarlinton LC, et al.. Dual-time-point 18F-FDG-PET/CT imaging in the assessment of suspected malignancy: Dual-time-point PET/CT in malignancy. and transmitted securely. Do tumor necrosis factor inhibitors increase cancer risk in patients with chronic immune-mediated inflammatory disorders? National Library of Medicine Methods Retrospective chart review of 1000 sarcoidosis cases seen in our clinic from 2003 to 2008. Sarcoidosis and breast masses have similar features upon palpation. The lesion presented as a 1.4 cm nodule located in the right . Case Report Newman LS, Rose CS, Maier LA . We report 5 cases with histologically confirmed sarcoidosis and breast cancer diagnosed and treated at the Rabin Medical Center. Magnetic resonance imaging (MRI) changes could also be helpful in distinguishing sarcoidosis lesions from tumoral localizations. The neoplastic cells can be found on histological examination within a granulomatous reaction. The .gov means its official. Fine needle aspiration cytology of lymph node with metastatic undifferentiated carcinoma and granulomatous (sarcoid-like) reaction. reported that non-Hodgkin lymphoma was the most frequently declared cause of death in women when sarcoidosis was not the underlying cause of death, especially after the age of 50 (4). Although its etiology is still unknown; sarcoidosis is thought to be the consequence of an exaggerated immune response to an environmental trigger in a genetically predisposed patient. Histological diagnosis is difficult if the pathologist is not aware of the suspected diagnosis of LYG or unfamiliar with this condition. Any atypical and unexplained symptom mimicking a sarcoidosis flare should encourage the clinician to be careful to differential diagnosis. Pathological specimens were evaluated for the presence of non-caseating granulomas consistent with sarcoidosis and for the manifestation of proliferative breast disease. There is currently no alternative to the histological examination to differentiate sarcoidosis from neoplasia. Our report presents the first case series among the Jewish population, in particular Ashkenazi Jewish females, where the incidence rate for breast cancer is higher. Despite conflicting data, the overall cancer risk in sarcoidosis patients is clearly higher than in the general population. Longcope WT, Freiman DG. Schimmelpennink MC, Vorselaars ADM, van Beek FT, Crommelin HA, Deneer VHM, Keijsers RGM, et al.. Efficacy and safety of infliximab biosimilar Inflectra in severe sarcoidosis. Accordingly, sarcoidosis can mimic breast cancer, making the differential diagnosis very difficult. the contents by NLM or the National Institutes of Health. Pathological diagnosis could sometimes be challenging since very few tumor cells may be surrounded by massive granulomatous reaction. Brincker H. Solid tumors preceding or following sarcoidosis. Dual time point 18-FDG PET-CT with delayed acquisition sequences and 18F-3-Fluoro-3-deoxythymidine (18F-FLT) PET-CT could help in distinguishing malignant from non-malignant lesions but few studies are available and their roles in improving the diagnostic performances of PET-CT remain to be precised (116, 117). This causes organ inflammation. Primary sarcoidosis of the breast: case description and review of the In a patient with previously known sarcoidosis, the occurrence of atypical manifestations (e.g., peritoneal or gut involvement) or new organ involvement, and refractory disease which is defined as a disease in which a 2nd line treatment is not sufficient to achieve satisfying disease control or satisfying CS tapering, must lead to histological confirmation to rule out opportunistic infection and lymphoma, especially (31, 102, 108). Likewise, London et al. Sarcoidosis may be triggered by your body's. Shigemitsu H. Is sarcoidosis frequent in patients with cancer? TE contributed to bibliography, most of writing, and reviewing of the manuscript. SLR disappeared with drug discontinuation in 17.7% of the cases. 2020 The Authors. Marquet A, Chapelon-Abric C, Maucort-Boulch D, Cohen-Aubart F, Prard L, Bouillet L, et al.. Efficacy and safety of TNF antagonists in ocular sarcoidosis: data from the French registry STAT. When sarcoidosis is suspected histological diagnosis is mandatory. Most frequently the diagnosis of sarcoidosis was made after 40 years old and the most frequent type of lymphoma was HL. Mammary sarcoidosis is a rare clinical entity. Going JJ, Anderson TJ, Wilkinson S, Chetty U. Granulomatous lobular mastitis. Indeed, in this series, the risk of lymphoma was 11 times higher in the sarcoidosis group, compared to the expected risk of lymphoma in the general population. Compared to the general population, sarcoidosis patients had a 5.5-fold higher risk of developing lymphoma (14). CS may help control ICI-induced SLR without holding cancer treatments. The median age at the onset of sarcoidosis was 49 years. Rybicki BA, Major M, Popovich J Jr, Maliarik MJ, Iannuzzi MC. Sarcoidosis is a condition that causes lumps or nodules (granulomas) to form in your lungs, lymph nodes, skin, eyes and other parts of your body. In all our patients, the physical findings of a mass and palpable axillary node (in 1 patient) could be attributed to either a malignancy or an inflammatory granulomatous process. The average interval between the diagnosis of sarcoidosis and breast cancer was 9 years and 6 months. Since the individualization of sarcoidosis-lymphoma association by Brincker et al., the relationship between sarcoidosis or granulomatous syndromes and malignancies has been clarified through observational studies worldwide. The differentiation between breast involvement of sarcoidosis and malignancy is difficult clinically and radiologically, and histological study is necessary when this association is suspected. The diagnosis was established on the basis of clinical and radiological findings. Although some imaging results may point to a diagnosis of neoplasia [e.g., asymmetric lymphadenopathy, hypermetabolism of extrathoracic lymph nodes; (78)], 18-fluorodeoxyglucose (18-FDG) uptake on PET-CT is unable to differentiate malignant from non-malignant hypermetabolism. But it can also affect the eyes, skin, heart and other organs. There are currently no formal recommendations to guide the differential diagnosis workup between the evolution of lymphoma or a solid cancer and a granulomatous reaction associated with neoplasia. Pulmonary sarcoidosis simulating metastatic breast cancer. Lococo F, Muoio B, Chiappetta M, Nachira D, Petracca Ciavarella L, Margaritora S, et al. Seve P, Jamilloux Y, Gerfaud-Valentin M, El-Jammal T, Pavic M. Faut-il rechercher un cancer aprs la dcouverte d'une granulomatose inexplique? Song JY, Pittaluga S, Dunleavy K, Grant N, White T, Jiang L, et al.. Lymphomatoid granulomatosisa single institute experience: pathologic findings and clinical correlations. sharing sensitive information, make sure youre on a federal This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Breast sarcoidosis often mimics carcinomas at clinical examination. Sarcoidosis is a multisystemic disease that may involve the breast parenchyma and can be confused with benign or malignant tumors. Rizzato G. Extrapulmonary presentation of sarcoidosis. The mass was located in the left breast in 21 (57%) patients and in the right breast in 15 (40%) patients; 1 (3%) patient had bilateral breast masses. Sarcoidosis of the breast. Sarcoid-like reaction in patients with malignant tumors: Long-term Since this was a review of the literature and not a meta-analysis, no data extraction occurred. How does BAFF activate B cells in patients with autoimmune diseases? Accordingly, sarcoidosis can mimic breast cancer, making the differential diagnosis very difficult. Sarcoidosis is an idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. Lower EE, Hawkins HH, Baughman RP. Pulmonary function testing and chest CT have to be performed in order to assess sarcoidosis severity. Sarcoidosis has a tendency to present between the ages of 20 and 49 years [44]. This study reports a case of non-luminal HER-2/neu-positive breast cancer in a patient presenting non-caseating epithelioid cell granulomas of sarcoidosis after treatment and initially suspected to have metastatic disease. Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet P-Y, Mller-Quernheim J. Nardi A, Brillet P-Y, Letoumelin P, Girard F, Brauner M, Uzunhan Y, et al.. Brincker reported that 37% of primary tumor sites may present with epithelioid cell granulomas (9). London J, Grados A, Ferm C, Charmillon A, Maurier F, Deau B, et al.. Sarcoidosis occurring after lymphoma: report of 14 patients and review of the literature. Sarcoidosis of the breast. Increased risk for cancer following sarcoidosis. reported that almost 60% of sarcoidosis cases occurring after a cancer were diagnosed within 1 year of cancer diagnosis (58). Our findings showed no further evidence of systemic sarcoidosis after initial evaluation, wherein most of the SLR lesions decreased or did not change during follow-up. Sarcoidosis as a paraneoplastic syndrome for breast cancer. There was strong suspicion of metastatic disease from breast carcinoma. Sarcoidlike reaction in patients with malignancy. Most patients had a history of high stage lymphoma (Ann Harbor III or IV) (74%). Signs and symptoms of the malignancy at presentation were reported in detail in 26 patients, of whom 24 (92%) had a self-detected mass, and 1 (4%) had nipple retraction and a peau d'orange appearance; in 1 (4%) patient the mass was detected during routine gynecologic examination. Sarcoidosis and Cancer: A Complex Relationship - PubMed Risbano MG, Groshong SD, Schwarz MI. Two cases and literature review. Cutaneous Sarcoidosis Linked with Recurrence of Breast Cancer in Careers, Unable to load your collection due to an error. Sarcoidosis is a chronic inflammatory disease of unknown etiology, which can involve different organs and systems. Sarcoidosis is an inflammatory disease in which granulomas, or clumps of inflammatory cells, form in various organs. Barba T, Marquet A, Bouvry D, Cohen-Aubart F, Ruivard M, Debarbieux S, et al.. Efficacy and safety of infliximab therapy in refractory upper respiratory tract sarcoidosis: experience from the STAT registry. Schattenberg AVMB, Baynes C, van Dijk MCR F, Koster A, van Cleef PHJ, Preijers FWMB, et al.. A mediastinal mass after donor lymphocyte infusion for relapse of chronic myeloid leukemia after allogeneic stem cell transplantation. Breast cancer is the most common cancer among women. first reported an increased risk of cancer in sarcoidosis patients (7). In a few patients, drug reintroduction triggered SLR recurrence. Takahashi R, Shibuya Y, Shijubo N, Asaishi K, Abe S. Mammary involvement in a patient with sarcoidosis. In case of atypical sarcoidosis, lymphocytes phenotyping should be performed in order to rule out clonality. Akaike G, Itani M, Shah H, Ahuja J, Yilmaz Gunes B, Assaker R, et al.. PET/CT in the diagnosis and workup of sarcoidosis: focus on atypical manifestations. Stage IV sarcoidosis: comparison of survival with the general population and causes of death. official website and that any information you provide is encrypted Recent cancer immunotherapies, including immune checkpoint inhibitors (targeting PD-1, PD-L1, or CTLA-4) and BRAF or MEK inhibitors were also reported as possible inducers of sarcoidosis-like reactions. Only 1 of the patients with breast cancer and sarcoidosis identified in the present review was male. The risk of developing solid neoplasia or hematological malignancies, especially lymphomas, is increased in sarcoidosis patients. Breast cancer may contribute to the development of sarcoidosis. Sarcoidosis and Cancer Risk - CHEST Clarnette RM, Trotter J, Michell PA. A case of mammary sarcoidosis. It is noteworthy that sarcoidosis has been reported to increase levels of CA 15-3 in some cases [60], so the presence of this biomarker might be misleading. government site. A 3-year-long prospective observational study. Metastatic breast cancer masquerading as sarcoidosis. We conducted a systematic review of all available data and performed a meta-analysis to better define and quantify the association between sarcoidosis and cancer. They take the form of subcutaneous nodules, most of the time erythematous and painful (113). Other authors have provided conflicting data regarding other types of cancers, especially non-small lung carcinoma in which the presence of granulomas was not associated with better prognosis (65, 66). Sarcoidosis Presenting as Spiculated Breast Masses The https:// ensures that you are connecting to the Most of the time, lymphoma occurs 28 years after the sarcoidosis diagnosis, preferentially in patients with a chronic course of the disease (14). Two women with breast carcinoma developed bilateral hilar adenopathy, with pulmonary infiltrate in one, during treatment for breast carcinoma. Kristinsson S, Landgren O, Sjberg J, Turesson I, Bjrkholm M, Goldin L. Autoimmunity and risk for Hodgkin's lymphoma by subtype. Sarcoidosis of the breast: A rare case report and a review - ResearchGate 5 patients with a diagnosis of both sarcoidosis and breast cancer followed by the Rabin Medical Center between January 1993 and June 2012 were enrolled in this study. The site is secure. Sarcoidosis and neoplasia, especially lymphoma, can show overlapping presentations, thus making the diagnosis and treatment harder to deal with. DeFilippis EM, Kagan Arleo E. New diagnosis of sarcoidosis during treatment for breast cancer, with radiologic-pathologic correlation. sharing sensitive information, make sure youre on a federal The patient's race, reported in 29 patients, was Caucasian in 21 (72%), Black in 6 (21%), and Asian in 2 (7%). aDepartment of Surgery, Rabin Medical Center, Beilinson Campus, Petach Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, bUS Army Institute of Surgical Research, Fort Sam, Houston, TX, USA. Marchal A, Charlotte F, Maksud P, Haroche J, Lifferman F, Miyara M, et al.. Sarcoidosis flare after autologous stem cell transplantation: an immune paradox? In a French epidemiological study of 2417 patients, the cause of death was linked to neoplasms in 1.8% of the patients. In both populations reviewed, the average age at diagnosis of sarcoidosis and breast cancer was 57 years. A case report. The authors declare that they have no conflict of interest. A case of sarcoidosis in a patient with testicular cancer post stem cell transplant. Gusakova I, Lavrenkov K, Ariad S, Mermershtain W. Pulmonary sarcoidosis mimicking metastases in breast cancer patients. In this study, strong associations were found between SLR and several drugs including, pembrolizumab, nivolumab, ipilimumab (n = 103) along with dabrafenib, vemurafenib, trametinib, and cobimetinib (n = 37) (76). Bonifazi M, Bravi F, Gasparini S, La Vecchia C, Gabrielli A, Wells AU, et al.. Valeyre D, Soler P, Clerici C, Pr J, Battesti JP, Georges R, et al.. Sarcoidosis is a systemic disease of unknown etiology, characterized by the presence of non-caseating granulomas in various organs, mainly the lungs, and the lymphatic system. Typical and atypical manifestations of intrathoracic sarcoidosis. Hartel PH, Shilo K, Klassen-Fischer M, Neafie RC, Franks TJ. Atypical radiological manifestations should also be considered. 5 patients with a diagnosis of both sarcoidosis and breast cancer followed by the Rabin Medical . Although most of the patients reported in the literature may be assumed to have undergone mammography or ultrasound, the majority of publications did not mention the results of imaging studies. Sarcoidosis has also been reported in hematopoietic stem cell transplant recipients. Simultaneous occurrence of dermatomyositis and systemic sarcoidosis with recurrent breast cancer. These patients were on average 10 years older at the sarcoidosis diagnosis compared to unselected patients in most series (96, 97). Reported in 34 patients, mass size at presentation ranged from 1 to 7 cm. Before by Diogo Pinto October 4, 2018 A 49-year-old woman in Australia was simultaneously diagnosed with a rare case of cutaneous sarcoidosis and recurrent metastatic breast cancer, according to a case report. Dejhansathit S, Miller AM, Suvannasankha A. Among the neoplasia which can mimic sarcoidosis, special attention should be paid to lymphomatoid granulomatosis (LYG). In some cases, a specific condition called donor-acquired sarcoidosis was described (52, 82, 84, 85). Sarcoidosis of the breast coexisting with mammary carcinoma. Sarcoidosis Presenting As Metastatic Lymphadenopathy in Breast Cancer Bassler R, Birke F. Histopathology of tumor associated sarcoid-like stromal reaction in breast cancer. Endobronchial ultrasound-guided transbronchial needle aspiration Although rarely observed, physicians should be aware that sarcoidosis can present itself as a pseudo tumoral condition such as miliary nodules, peritoneal involvement, and symptomatic osteolytic or osteoblastic lesions (102104). Accordingly, sarcoidosis can mimic breast cancer, making the differential diagnosis very difficult. Salahuddin M, Karanth S, Ocazionez D, Estrada-Y-Martin RM, Cherian SV. ciated with cancer, including breast cancer. Criado E, Snchez M, Ramrez J, Arguis P, de Caralt TM, Perea RJ, et al.. Chorti E, Kanaki T, Zimmer L, Hadaschik E, Ugurel S, Gratsias E, et al.. Drug-induced sarcoidosis-like reaction in adjuvant immunotherapy: increased rate and mimicker of metastasis. Breast Care (Basel) 10: 137-140. Introduction Sarcoidosis is a granulomatous disease that can affect any organ system. The same is true for other diagnostic studies. In a series of 29 sarcoidosis patients with pre-existing cancer, Arish et al. Sarcoidosis diagnosis requires three major conditions: (1) a compatible clinical/radiological presentation, (2) evidence of granulomas on a biopsy sample, and (3) exclusion of differential diagnoses (101). FOIA Isolated mediastinal lymphadenopathy without hilar lymph node enlargement, non-lymphatic diffuse lung micronodules, cavitary mass on chest X-ray should also be considered as suspicious for a differential diagnosis of sarcoidosis (106, 107). Gallimore AP, George CD, Lampert IA. Alexandrescu DT, Kauffman CL, Ichim TE, Riordan NH, Kabigting F, Dasanu CA. Many alternative diagnoses mimicking sarcoidosis can also be encountered in a neoplastic context (Table 2). The presence of sarcoidosis and breast cancer in the same patient is uncommon but sarcoidosis can mimic breast cancer. While sarcoidosis is a well-defined condition, SLR is usually defined as non-caseating granulomatous reaction occurring under various conditions, which do not meet the diagnostic criteria for sarcoidosis (32). the contents by NLM or the National Institutes of Health. Prior JT. We report a case of breast sarcoidosis detected during screening mammography in a 57-year-old woman. LYG is a lymphoproliferative disorder associated with Epstein Barr virus (EBV). Female gender is associated with a relative risk of 1.3 [44]. Ji J, Shu X, Li X, Sundquist K, Sundquist J, Hemminki K. Cancer risk in hospitalized sarcoidosis patients: a follow-up study in Sweden. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group, Possible transmission of sarcoidosis via allogenic bone marrow transplantation. Viswanath L, Pallade S, Krishnamurthy B, Naveen T, Preethi BL, Pramod KP, Reddy O, Padma G. Darier-Roussy sarcoidosis mimicking metastatic breast cancer. These SLR can also mimic cancer progression or metastases. and transmitted securely. As a library, NLM provides access to scientific literature. Mitchell DN, Scadding JG, Heard BE, Hinson KF. Gamperl I, Enzinger C, Pichler A, Feichtinger M, Schlager T, Fertl E. Can pulmonary sarcoidosis trigger a progressive multifocal leukoencephalopathy? Recently, the American thoracic society (ATS) provided new guidelines concerning sarcoidosis diagnosis (32). We provide a brief literature review performed through the PubMed platform (https://www.pubmed.ncbi.nlm.nih.gov) using the keywords sarcoidosis, cancer, lymphoma, sarcoidosis-lymphoma syndrome, sarcoid-like reaction and drug-induced sarcoidosis that allowed us to find most of the references used to build this article. CD4/CD8 lymphocyte ratio in BALF is also higher in patients with sarcoidosis-lymphoma syndrome compared to unselected patients (98). Localized tubercoloid granulomas associated with carcinomas. The shared characteristics of the 2 diseases suggest that breast cancer and sarcoidosis may have a similar pathogenesis. Teo M, McCarthy JE, Brady AP, Curran DR, Power DG. Hence, we cannot reach conclusions regarding the effectiveness of various imaging techniques in the differential diagnosis of sarcoidosis with breast involvement and breast cancer. Results 429/1000 female sarcoidosis cases were identified. Spiekermann C, Kuhlencord M, Huss S, Rudack C, Weiss D. Coexistence of sarcoidosis and metastatic lesions: a diagnostic and therapeutic dilemma. Risk of Sarcoidosis May Be Associated with Breast Cancer, Study Finds Shah AK, Solomon L, Gumbs MA. Although sarcoidosis is considered to be a rare manifestation in breast cancer, it is conceivable that this may be an under-representation. Bethesda, MD 20894, Web Policies Before Sarcoidosis was frequently diagnosed at an early stage, possibly due to a more systematic follow-up with computed tomography (CT) and positron emission tomography in cancer patients. One patient had axillary lymph nodes involved with noncaseating granulomas, but no sarcoidosis was found in the breast of any of the women in their study. Multiple doughnut granulomas in a liver transplant patient with CMV reactivation. Based on our clinical cases and literature review, a histologic study is highly recommended over imaging if sarcoidosis or breast cancer is suspected in a Jewish female.