- Email: [email protected]
Invasive lobular carcinoma of the male breast: A rare histology of an uncommon disease
Journal of the Egyptian National Cancer Institute (2016) 28, 55–58
Cairo University
Journal of the Egyptian National Cancer Institute www.elsevier.com/locate/jnci www.sciencedirect.com
Case Report
Invasive lobular carcinoma of the male breast: A rare histology of an uncommon disease Rituraj Upadhyay a,*, Pavnesh Kumar a, D.N. Sharma a, Haresh K.P. a, Subhash Gupta a, P.K. Julka a, G.K. Rath a, Himani Bhankar b a b
Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi 110029, India Department of Pathology, Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi 110049, India
Received 30 August 2015; revised 11 October 2015; accepted 12 October 2015 Available online 31 October 2015
KEYWORDS Male breast carcinoma; Lobular carcinoma; Radiotherapy
Abstract Male breast carcinoma is a rare malignancy comprising less than 1% of all breast cancers. It is a serious disease with most patients presenting in advanced stages. Infiltrating ductal carcinoma is the most common histology while lobular carcinoma represents less than 1% of all these tumors. We report a case of locally advanced lobular carcinoma of breast in a 60 year old male. Ó 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of National Cancer Institute, Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
Introduction Male breast carcinoma is an extremely rare malignancy comprising less than 1% of all breast cancers and less than 1.5% of all malignancies in men [1,2]. The diagnosis is usually delayed until advanced stage, accounting for poor outcome [3]. The most common histologies in male breast carcinoma are infiltrating ductal carcinomas (about 74–95%) and papillary carcinoma (3–4%) [3,4]. Lobular carcinoma represents only 1% of all these tumors [5,6]. We here present a case of locally advanced lobular carcinoma of male breast. Case report A sixty year old male presented with right breast nodule, progressively increasing in size since 4 months. He had a history * Corresponding author. Mobile: +91 9717180564. E-mail address: [email protected] (R. Upadhyay). Peer review under responsibility of The National Cancer Institute, Cairo University.
of remission and recurrence of a right breast swelling since two years. He also complained of pain in right leg since 20 days. He was married and had 2 live and healthy children. There were no associated comorbidities or history of hormonal use. He used to chew tobacco since the age of 20 years. On clinical examination there was an irregular, hard, painless, well-defined, swelling fixed to the chest wall, measuring 8 4 cm and involving the supra-areolar medial and lateral quadrants. Overlying skin was hyper pigmented and there were satellite nodules involving the surrounding skin. Ipsilateral axillary lymph nodes were palpable and mobile. Histopathological findings Biopsy from the breast lump showed features of an invasive lobular carcinoma. Tumor cells were arranged in cords and trabeculae within the stroma forming an Indian-file pattern (Fig. 1A). The tumor cells were small, showing mild pleomorphism with scant to moderate amount of eosinophilic to clear cytoplasm, round nucleus with vesicular chromatin
http://dx.doi.org/10.1016/j.jnci.2015.10.001 1110-0362 Ó 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of National Cancer Institute, Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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Figure 1
Photomicrograph showing 200 (A) and 400 (B) view of tumor cells (both H&E stained sections).
and inconspicuous nucleoli. No mitosis was seen (Fig. 1B). On immunohistochemistry, tumor cells showed strong positivity for Estrogen receptors (Allred score 8), progesterone receptors (Allred score 8) and negativity for Her-2/neu receptors. Cell membrane was stained negative for E-cadherin. (Fig. 2) PET-CT done for metastatic work-up showed an FDG avid mass (3.5 8.0 cm) in the right breast, infiltrating the chest wall in the central region with involvement of the overlying skin and multiple FDG avid satellite nodules. Multiple FDG avid right axillary lymph nodes and extensive skeletal metastases were present (Fig. 3).
Disease was staged clinically as cT4N1M1 (stage IV). Treatment Palliative radiotherapy was given to right breast nodule, skeletal weight bearing and painful areas. He received palliative chemotherapy with cyclophosphamide 500 mg/m2, epirubicin 80 mg/m2 and 5-FU 500 mg/m2. Post 6 cycles of chemotherapy PET-CT done for response assessment showed partial response to treatment. Then the patient was started on tamoxifen 20 mg daily.
Figure 2 Immunohistochemistry: Positive nuclear staining for ER (A) and PR (B), negative staining for Her-2/neu (C), and E-cadherin (D).
Invasive Lobular Carcinoma of the Male Breast
Figure 3
57
PET images showing the primary disease in breast (A) and metastases at multiple skeletal sites (B and C).
Discussion The majority of patients with male breast cancer present with a palpable mass and/or visible nipple changes [5]. The median age at diagnosis is in 6th decade [4]. Although some factors favor early detection, like thin soft tissue, the interval between first complaints and diagnosis is usually longer, so the tumor is advanced in most cases at the time of initial diagnosis, contributing to poorer outcome. Because of its diffuse growth pattern and tendency to form lesions with opacity equal to or less than that of the breast parenchyma, invasive lobular carcinoma can be extremely difficult to detect mammographically, potentially adding to delay in diagnosis when compared to invasive ductal carcinoma [7]. The predisposing factors for male breast cancer are mostly unknown. Numerous etiologies have been elucidated, such as genetic mutations, especially BRCA2, and conditions associated with an imbalance between estrogen and testosterone. Certain medications, such as cimetidine [8], are hypothesized to increase the risk for male breast cancer via an estrogenic mechanism. Some other associated risk factors are undescended testes, congenital inguinal hernia, orchiectomy, orchitis, testicular injury, infertility and Klinefelters syndrome [2,6]. Mutations of either the BRCA1 or the BRCA2 gene are thought to be found in 4–40% of
men with breast cancer, with BRCA2 mutation being more frequent [5]. A positive family history of breast carcinoma may be an important contributor [9]. Although tobacco smoking and alcohol do not appear to be carcinogenic for male breast cancer, [10] our patient had a significant history of tobacco chewing. Although lobular carcinoma of the female breast is relatively common, comprising approximately 15% of all cases of female breast cancer, in males this histopathologic pattern is exceedingly rare, because lobules and acini are not found in normal male breast tissue [11]. Estrogen has a profound effect on male breast tissue and is liable to stimulate formation of acini and lobules identical to those of female breast. The first case of invasive lobular carcinoma in a male patient without known estrogen exposure was described in 1989 [12]. Evaluation of 2537 male breast cancer cases from the SEER database between 1973 and 1998 found 1.5% invasive lobular carcinomas [2]. The highest percentage, 4.2%, was noted by Nahleh et al. [3] who analyzed the Veterans Affairs Central Cancer registry with 612 male breast cancer patients. But none of these studies were able to review the original pathology for confirmation of the lobular histology. Treatment of male breast cancer remains controversial. The lower incidence of invasive lobular carcinoma in men likely explains the lack of studies focusing on the treatment of this
58 tumor type. Clinical knowledge of male breast cancers overall derives mostly from single institutional retrospective studies and from database studies. In general, most principles are similar to those of female breast cancer. Total mastectomy with axillary dissection is the optimum local therapy for carcinoma of the male breast [13]. Radiation therapy does appear to be effective in preventing local recurrences in male patients, but all studies have been underpowered to address the question of a potential survival benefit [14]. Male breast cancer patients do tend to be treated with radiation therapy after mastectomy more often than females, perhaps because they are more likely to have nipple or skin involvement [15]. Studies have shown that the presence of infiltrating lobular histology should not influence decisions regarding local radiation therapy [16]. Palliative radiotherapy has a proven role in management of metastatic disease [17]. Although the evidence is limited, most studies support a benefit for both adjuvant chemotherapy and tamoxifen in male breast cancer, particularly when the prognosis is poor [18]. Carcinomas of the male breast have higher rate of hormone receptor positivity (80–85%) than do those of the female breast when matched for tumor stage, grade and patient age [5]. Our patient also presented at an advanced stage of disease with multiple metastases. We treated our patient with palliative radiotherapy, chemotherapy, followed by tamoxifen in view of ER positivity. There was partial response after chemotherapy. On tamoxifen there was excellent disease control with palliation of symptoms. He is still alive after 20 months of initial diagnosis. Conclusion Invasive lobular carcinoma of male breast is a rare entity and poses as a diagnostic and therapeutic difficulty in view of its uncommon histology and late presentation. This diagnosis should be suspected early and treated aggressively with multimodality approach. Further large adequately powered studies should be conducted to define clear treatment guidelines. Presentation at meeting None. Financial disclosers (all authors) None. Conflict of interest We have no conflict of interest to declare.
R. Upadhyay et al. References [1] Yoney A, Kucuk A, Unsal M. Male breast cancer: a retrospective analysis. Cancer Radiother 2009;13(2):103–7. [2] Giordano SH, Buzdar AU, Hortobaghyi GN. Breast cancer in men. Ann Intern Med 2002;137:678–87. [3] Nahleh ZA, Srikantiah R, Safa M, Jazieh AR, Muhleman A, Komrokji R. Male breast cancer in the veterans affairs population: a comparative analysis. Cancer 2007;109:1471–7. [4] Agrawal A, Ayantunde AA, Rampaul R, Robertson JF. Male breast cancer: a review of clinical management. Breast Cancer Res Treat 2007;103:11–21. [5] Rudlowski C. Male breast cancer. Breast Care 2008;3:183–9. [6] Bethesda MD. Surveillance, epidemiology and end results (SEER) program. Public use data (1993–1997). National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program. Cancer Statistics Branch; April 2000. [7] Hilleren DJ, Andersson IT, Lindholm K, Linnell FS. Invasive lobular carcinoma: mammographic findings in a 10-year experience. Radiology 1991 Jan;178(1):149–54. [8] San Miguel P, Sancho M, Enriquez JL, Fernandez J, GonzalezPalacios F. Lobular carcinoma of the male breast associated with the use of cimetidine. Virchows Arch 1997;430:261–3. [9] Chikaraddi SB, Krishnappa R, Deshmane V. Male breast cancer in Indian patients: is it the same? Indian J Cancer 2012 Jul– Sep;49(3):272–6. [10] Cook MB, Gue´nel P, Gapstur SM, van den Brandt PA, Michels KB, Casagrande JT, et al. Tobacco and alcohol in relation to male breast cancer: an analysis of the male breast cancer pooling project consortium. Cancer Epidemiol Biomarkers Prev 2015 Mar;24(3):520–31. [11] Salvadori B, Saccozzi R, Manzari A, Andreola S, Conti RA, Cusumano F, et al. Prognosis of breast cancer in males: an analysis of 170 cases. Eur J Cancer 1994;30 A:930–5. [12] Nance KV, Reddick RL. In situ and infiltrating lobular carcinoma of the male breast. Hum Pathol 1989;20:1220–2. [13] Cutuli B, Lacroze M, Dilhuydy JM, Velten M, De Lafontan B, Marchal C, et al. Male breast cancer: results of the treatments and prognostic factors in 397 cases. Eur J Cancer 1995;31A:1960–4. [14] Giordano SH. A review of the diagnosis and management of male breast cancer. Oncologist 2005 Aug;10(7):471–9. [15] Scott-Conner CE, Jochimsen PR, Menck HR, Winchester DJ. An analysis of male and female breast cancer treatment and survival among demographically identical pairs of patients. Surgery 1999;126:775–80, discussion 780–781. [16] Peiro G, Bornstein BA, Connolly JL, Gelman R, Hetelekidis S, Nixon AJ, et al. The influence of infiltrating lobular carcinoma on the outcome of patients treated with breast-conserving surgery and radiation therapy. Breast Cancer Res Treat 2000 Jan;59(1):49–54. [17] Zabel A, Milker-Zabel S, Zuna I, Wannenmacher M, Debus J. External beam radiotherapy in the treatment of male breast carcinoma: patterns of failure in a single institute experience. Tumori 2005 Mar–Apr;91(2):151–5. [18] Donegan WL, Redlich PN, Lang PJ, Gall MT. Carcinoma of the breast in males: a multi-institutional survey. Cancer 1998;83:498–509.
Cairo University
Journal of the Egyptian National Cancer Institute www.elsevier.com/locate/jnci www.sciencedirect.com
Case Report
Invasive lobular carcinoma of the male breast: A rare histology of an uncommon disease Rituraj Upadhyay a,*, Pavnesh Kumar a, D.N. Sharma a, Haresh K.P. a, Subhash Gupta a, P.K. Julka a, G.K. Rath a, Himani Bhankar b a b
Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi 110029, India Department of Pathology, Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi 110049, India
Received 30 August 2015; revised 11 October 2015; accepted 12 October 2015 Available online 31 October 2015
KEYWORDS Male breast carcinoma; Lobular carcinoma; Radiotherapy
Abstract Male breast carcinoma is a rare malignancy comprising less than 1% of all breast cancers. It is a serious disease with most patients presenting in advanced stages. Infiltrating ductal carcinoma is the most common histology while lobular carcinoma represents less than 1% of all these tumors. We report a case of locally advanced lobular carcinoma of breast in a 60 year old male. Ó 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of National Cancer Institute, Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
Introduction Male breast carcinoma is an extremely rare malignancy comprising less than 1% of all breast cancers and less than 1.5% of all malignancies in men [1,2]. The diagnosis is usually delayed until advanced stage, accounting for poor outcome [3]. The most common histologies in male breast carcinoma are infiltrating ductal carcinomas (about 74–95%) and papillary carcinoma (3–4%) [3,4]. Lobular carcinoma represents only 1% of all these tumors [5,6]. We here present a case of locally advanced lobular carcinoma of male breast. Case report A sixty year old male presented with right breast nodule, progressively increasing in size since 4 months. He had a history * Corresponding author. Mobile: +91 9717180564. E-mail address: [email protected] (R. Upadhyay). Peer review under responsibility of The National Cancer Institute, Cairo University.
of remission and recurrence of a right breast swelling since two years. He also complained of pain in right leg since 20 days. He was married and had 2 live and healthy children. There were no associated comorbidities or history of hormonal use. He used to chew tobacco since the age of 20 years. On clinical examination there was an irregular, hard, painless, well-defined, swelling fixed to the chest wall, measuring 8 4 cm and involving the supra-areolar medial and lateral quadrants. Overlying skin was hyper pigmented and there were satellite nodules involving the surrounding skin. Ipsilateral axillary lymph nodes were palpable and mobile. Histopathological findings Biopsy from the breast lump showed features of an invasive lobular carcinoma. Tumor cells were arranged in cords and trabeculae within the stroma forming an Indian-file pattern (Fig. 1A). The tumor cells were small, showing mild pleomorphism with scant to moderate amount of eosinophilic to clear cytoplasm, round nucleus with vesicular chromatin
http://dx.doi.org/10.1016/j.jnci.2015.10.001 1110-0362 Ó 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of National Cancer Institute, Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
56
R. Upadhyay et al.
Figure 1
Photomicrograph showing 200 (A) and 400 (B) view of tumor cells (both H&E stained sections).
and inconspicuous nucleoli. No mitosis was seen (Fig. 1B). On immunohistochemistry, tumor cells showed strong positivity for Estrogen receptors (Allred score 8), progesterone receptors (Allred score 8) and negativity for Her-2/neu receptors. Cell membrane was stained negative for E-cadherin. (Fig. 2) PET-CT done for metastatic work-up showed an FDG avid mass (3.5 8.0 cm) in the right breast, infiltrating the chest wall in the central region with involvement of the overlying skin and multiple FDG avid satellite nodules. Multiple FDG avid right axillary lymph nodes and extensive skeletal metastases were present (Fig. 3).
Disease was staged clinically as cT4N1M1 (stage IV). Treatment Palliative radiotherapy was given to right breast nodule, skeletal weight bearing and painful areas. He received palliative chemotherapy with cyclophosphamide 500 mg/m2, epirubicin 80 mg/m2 and 5-FU 500 mg/m2. Post 6 cycles of chemotherapy PET-CT done for response assessment showed partial response to treatment. Then the patient was started on tamoxifen 20 mg daily.
Figure 2 Immunohistochemistry: Positive nuclear staining for ER (A) and PR (B), negative staining for Her-2/neu (C), and E-cadherin (D).
Invasive Lobular Carcinoma of the Male Breast
Figure 3
57
PET images showing the primary disease in breast (A) and metastases at multiple skeletal sites (B and C).
Discussion The majority of patients with male breast cancer present with a palpable mass and/or visible nipple changes [5]. The median age at diagnosis is in 6th decade [4]. Although some factors favor early detection, like thin soft tissue, the interval between first complaints and diagnosis is usually longer, so the tumor is advanced in most cases at the time of initial diagnosis, contributing to poorer outcome. Because of its diffuse growth pattern and tendency to form lesions with opacity equal to or less than that of the breast parenchyma, invasive lobular carcinoma can be extremely difficult to detect mammographically, potentially adding to delay in diagnosis when compared to invasive ductal carcinoma [7]. The predisposing factors for male breast cancer are mostly unknown. Numerous etiologies have been elucidated, such as genetic mutations, especially BRCA2, and conditions associated with an imbalance between estrogen and testosterone. Certain medications, such as cimetidine [8], are hypothesized to increase the risk for male breast cancer via an estrogenic mechanism. Some other associated risk factors are undescended testes, congenital inguinal hernia, orchiectomy, orchitis, testicular injury, infertility and Klinefelters syndrome [2,6]. Mutations of either the BRCA1 or the BRCA2 gene are thought to be found in 4–40% of
men with breast cancer, with BRCA2 mutation being more frequent [5]. A positive family history of breast carcinoma may be an important contributor [9]. Although tobacco smoking and alcohol do not appear to be carcinogenic for male breast cancer, [10] our patient had a significant history of tobacco chewing. Although lobular carcinoma of the female breast is relatively common, comprising approximately 15% of all cases of female breast cancer, in males this histopathologic pattern is exceedingly rare, because lobules and acini are not found in normal male breast tissue [11]. Estrogen has a profound effect on male breast tissue and is liable to stimulate formation of acini and lobules identical to those of female breast. The first case of invasive lobular carcinoma in a male patient without known estrogen exposure was described in 1989 [12]. Evaluation of 2537 male breast cancer cases from the SEER database between 1973 and 1998 found 1.5% invasive lobular carcinomas [2]. The highest percentage, 4.2%, was noted by Nahleh et al. [3] who analyzed the Veterans Affairs Central Cancer registry with 612 male breast cancer patients. But none of these studies were able to review the original pathology for confirmation of the lobular histology. Treatment of male breast cancer remains controversial. The lower incidence of invasive lobular carcinoma in men likely explains the lack of studies focusing on the treatment of this
58 tumor type. Clinical knowledge of male breast cancers overall derives mostly from single institutional retrospective studies and from database studies. In general, most principles are similar to those of female breast cancer. Total mastectomy with axillary dissection is the optimum local therapy for carcinoma of the male breast [13]. Radiation therapy does appear to be effective in preventing local recurrences in male patients, but all studies have been underpowered to address the question of a potential survival benefit [14]. Male breast cancer patients do tend to be treated with radiation therapy after mastectomy more often than females, perhaps because they are more likely to have nipple or skin involvement [15]. Studies have shown that the presence of infiltrating lobular histology should not influence decisions regarding local radiation therapy [16]. Palliative radiotherapy has a proven role in management of metastatic disease [17]. Although the evidence is limited, most studies support a benefit for both adjuvant chemotherapy and tamoxifen in male breast cancer, particularly when the prognosis is poor [18]. Carcinomas of the male breast have higher rate of hormone receptor positivity (80–85%) than do those of the female breast when matched for tumor stage, grade and patient age [5]. Our patient also presented at an advanced stage of disease with multiple metastases. We treated our patient with palliative radiotherapy, chemotherapy, followed by tamoxifen in view of ER positivity. There was partial response after chemotherapy. On tamoxifen there was excellent disease control with palliation of symptoms. He is still alive after 20 months of initial diagnosis. Conclusion Invasive lobular carcinoma of male breast is a rare entity and poses as a diagnostic and therapeutic difficulty in view of its uncommon histology and late presentation. This diagnosis should be suspected early and treated aggressively with multimodality approach. Further large adequately powered studies should be conducted to define clear treatment guidelines. Presentation at meeting None. Financial disclosers (all authors) None. Conflict of interest We have no conflict of interest to declare.
R. Upadhyay et al. References [1] Yoney A, Kucuk A, Unsal M. Male breast cancer: a retrospective analysis. Cancer Radiother 2009;13(2):103–7. [2] Giordano SH, Buzdar AU, Hortobaghyi GN. Breast cancer in men. Ann Intern Med 2002;137:678–87. [3] Nahleh ZA, Srikantiah R, Safa M, Jazieh AR, Muhleman A, Komrokji R. Male breast cancer in the veterans affairs population: a comparative analysis. Cancer 2007;109:1471–7. [4] Agrawal A, Ayantunde AA, Rampaul R, Robertson JF. Male breast cancer: a review of clinical management. Breast Cancer Res Treat 2007;103:11–21. [5] Rudlowski C. Male breast cancer. Breast Care 2008;3:183–9. [6] Bethesda MD. Surveillance, epidemiology and end results (SEER) program. Public use data (1993–1997). National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program. Cancer Statistics Branch; April 2000. [7] Hilleren DJ, Andersson IT, Lindholm K, Linnell FS. Invasive lobular carcinoma: mammographic findings in a 10-year experience. Radiology 1991 Jan;178(1):149–54. [8] San Miguel P, Sancho M, Enriquez JL, Fernandez J, GonzalezPalacios F. Lobular carcinoma of the male breast associated with the use of cimetidine. Virchows Arch 1997;430:261–3. [9] Chikaraddi SB, Krishnappa R, Deshmane V. Male breast cancer in Indian patients: is it the same? Indian J Cancer 2012 Jul– Sep;49(3):272–6. [10] Cook MB, Gue´nel P, Gapstur SM, van den Brandt PA, Michels KB, Casagrande JT, et al. Tobacco and alcohol in relation to male breast cancer: an analysis of the male breast cancer pooling project consortium. Cancer Epidemiol Biomarkers Prev 2015 Mar;24(3):520–31. [11] Salvadori B, Saccozzi R, Manzari A, Andreola S, Conti RA, Cusumano F, et al. Prognosis of breast cancer in males: an analysis of 170 cases. Eur J Cancer 1994;30 A:930–5. [12] Nance KV, Reddick RL. In situ and infiltrating lobular carcinoma of the male breast. Hum Pathol 1989;20:1220–2. [13] Cutuli B, Lacroze M, Dilhuydy JM, Velten M, De Lafontan B, Marchal C, et al. Male breast cancer: results of the treatments and prognostic factors in 397 cases. Eur J Cancer 1995;31A:1960–4. [14] Giordano SH. A review of the diagnosis and management of male breast cancer. Oncologist 2005 Aug;10(7):471–9. [15] Scott-Conner CE, Jochimsen PR, Menck HR, Winchester DJ. An analysis of male and female breast cancer treatment and survival among demographically identical pairs of patients. Surgery 1999;126:775–80, discussion 780–781. [16] Peiro G, Bornstein BA, Connolly JL, Gelman R, Hetelekidis S, Nixon AJ, et al. The influence of infiltrating lobular carcinoma on the outcome of patients treated with breast-conserving surgery and radiation therapy. Breast Cancer Res Treat 2000 Jan;59(1):49–54. [17] Zabel A, Milker-Zabel S, Zuna I, Wannenmacher M, Debus J. External beam radiotherapy in the treatment of male breast carcinoma: patterns of failure in a single institute experience. Tumori 2005 Mar–Apr;91(2):151–5. [18] Donegan WL, Redlich PN, Lang PJ, Gall MT. Carcinoma of the breast in males: a multi-institutional survey. Cancer 1998;83:498–509.