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Annals of Surgical Oncology 9:663-667 (2002)
© 2002 Society of Surgical Oncology

ORIGINAL ARTICLES

Secretory Carcinoma of the Male Breast

Eelco de Bree, MD, John Askoxylakis, MD, Elpida Giannikaki, MD, Nikos Chroniaris, MD, Elias Sanidas, MD and Dimitris D. Tsiftsis, PhD

From the Departments of Surgical Oncology (EDB, JA, ES, DDT) and Pathology (EG), University Hospital, Medical School of Crete, Herakleion, Greece; and the Department of Pathology (NC), Venizeleio Hospital, Herakleion, Greece.

Correspondence: Address correspondence and reprint requests to: E. de Bree, Department of Surgical Oncology, University Hospital, PO Box 1352, 711 10 Herakleion, Greece; Fax: 30-810-542059; E-mail: debree{at}edu.uch.gr


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Secretory carcinoma is a distinctive and rare variant of breast carcinoma with a favorable prognosis because these tumors usually behave in an indolent manner. The occurrence of this type of breast cancer in males was studied.

Methods: An extensive literature survey concerning secretory breast cancer in males was performed. Data of one case treated in our institute were added.

Results: A total of 14 cases were identified, and our case was added to this series. The median age was 17 years. The duration of symptoms varied from 1 month to 21 years, and the tumor size was 1.2 to 4 cm. Surgical treatment varied from local excision only to modified radical mastectomy. Three patients received adjuvant treatment. Lymph nodes were involved in 3 of the 10 cases undergoing axillary lymph node dissection. The primary tumor was only 1.5 cm in diameter in two of those cases. None of the patients presented with systemic metastases. Only one male was reported to develop recurrence and consequently died of systemic disease.

Conclusions: Secretory breast cancer is very rare in males and seems to occur at a younger age in males than in females. A sufficient number of female cases have been reported with recurrence after local excision. Although in females lymph node metastases are rarely observed in secretory breast carcinoma smaller than 2 cm, in male patients nodal metastases might occur more frequently in smaller tumors. Therefore, mastectomy with sentinel lymph node biopsy or axillary lymph node dissection is recommended in any male case. Biological behavior seems to be similarly favorable in either sex.

Key Words: Secretory breast cancer • Male breast • Incidence • Treatment


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Carcinoma of the male breast is uncommon. It accounts for <1% of all breast cancer cases and comprises .2% of all cancers in males.1 As in females, the age-specific incidence of breast cancer in males increases steadily throughout life and is very rare in childhood and adolescence.1 Invasive ductal carcinoma predominates, accounting for 84% to 93% of cases.1 Lobular carcinoma was long thought not to occur in men because of the absence of lobules in the rudimentary male breast, but this is no longer the case. Lobules do appear in men under appropriate hormonal stimulation, and they can be found in cases of gynecomastia.2 Secretory carcinoma is a distinctive and rare variant of breast carcinoma with a favorable prognosis, because these tumors usually behave in an indolent manner.

Herein, we describe a case of a 17-year-old male with secretory breast carcinoma. An extensive literature survey was performed to collect all reported cases in males, and the data regarding treatment and outcome were analyzed.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Case Report
A 17-year-old male was referred to our hospital with the diagnosis of juvenile secretory cancer of the right breast. He had a 2-year history of a painful lump in his right breast. No nipple discharge was noticed. Initially, only bilateral gynecomastia was clinically diagnosed by his general practitioner, and no further action was undertaken. Because his symptoms persisted, he was finally referred to a surgeon. Physical examination revealed, besides bilateral gynecomastia, a painful, firm, mobile, and circumscribed subareolar lump of 3 cm in the right breast. Axillary and supraclavicular lymph nodes were not palpable. Mammography demonstrated bilateral gynecomastia with, at the right side, a subareolar, moderately circumscribed tumor 3 cm in diameter (Fig. 1). An excisional biopsy of the tumor was performed, and histological examination revealed a juvenile secretory breast cancer of 3 cm in diameter, with an in situ component extending close to the surgical margins. Solid proliferation of periodic acid-Schiff (PAS)-positive, mostly vacuolated, secretory cells formed lobulated structures. The tumor cells demonstrated little atypia and had relatively bland nuclei, without prominent nucleoli and with scarce mitosis (Fig. 2). The breast tissue at the vicinity of the carcinoma presented changes of gynecomastia.



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  		FIG. 1. Mammography of the right breast of a 17-year-old male with secretory breast cancer (left, face; right, craniocaudal).

 


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  		FIG. 2. Histological examination of secretory breast cancer in a 17-year-old male, demonstrating lobulated structure and solid growth of the carcinoma and consisting of cells with vacuolated cytoplasm (arrow). Hematoxylin and eosin, x100.

 
He was referred to our hospital for further diagnostic and therapeutic management. Serum tumor markers and other routine blood test results were normal. The hormonal profile was normal for his age. Evaluation with computed tomography of the chest and abdomen was negative for metastatic disease. Because of the extensive in situ component and the tumor size, a Madden modified radical mastectomy was performed. The surgical management of contralateral gynecomastia and unilateral nipple reconstruction was postponed for a reasonable period of follow-up examination. The postoperative course was uneventful. In the residual breast no malignant cells were identified. The 14 axillary lymph nodes removed were free of tumor cells. No adjuvant therapy was administered, and 9 months after initial diagnosis he remains free of disease.

Literature Review
An extensive literature survey using PubMed (1962–2001) and references in articles concerning this tumor was performed. Data regarding age, duration of symptoms, presence of gynecomastia, tumor characteristics, lymph node status, treatment decisions, and outcome were noted.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
A total of 14 cases of male patients with secretory breast carcinoma could be identified in the world literature.3–17 These data were added to those of the previously reported case. The mean and median ages were 21 and 17 years, respectively. Patient and tumor characteristics, treatment, and outcome are listed in Table 1. None of the patients presented with systemic metastases. Hormonal abnormalities were not detected in any of the patients. Treatment considerations made in the individual cases were rarely discussed and, if reported, therapeutic decisions were not based on comprehensible medical evidence because of the sporadic publication of cases.


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  		TABLE 1. Data on 15 male patients with secretory breast cancer
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Secretory breast carcinoma is a distinctive form of breast cancer originally described in 1966 by McDivitt and Stewart18 as "juvenile breast carcinoma" because it was thought to occur only in childhood. However, it has been seen to occur in all age groups, and the majority of patients are adults.4 Age at presentation varies from 3 to 87 years.5,18,19 Hence, the name was changed to secretory breast carcinoma.4 It is a very rare tumor. Lamovec and Bracko9 detected only 4 cases of secretory carcinoma in a retrospective series of 7038 breast carcinoma cases. Approximately 100 cases have been reported in the literature, and most patients were female.4 Our extensive literature survey revealed 14 cases of male patients with secretory breast cancer, resulting in a male-female ratio of approximately 1:6 for the total number of reported cases; this ratio is relatively high in comparison with the sex distribution for the usual histological types of breast cancer. Whether this reflects the real sex distribution or increased medical sensitivity to report the rarer male cases is unknown. Tavassolli and Norris4 found only 1 male in their series of 19 patients, in which the mean and median ages were 28 and 25 years, respectively. In a collected review of 22 pediatric patients, 4 males were identified.8 The mean age of those pediatric patients was 10 years. In a review series of 32 female adult patients, the mean and median age were 40 and 33 years, respectively.20 In our series, the male patients were significantly younger than those in the mixed series of Tavassolli and Norris.4 The age difference averaged almost a decade. Additionally, the higher percentage of male patients among the pediatric patients compared with the latter series also suggests prevalence of secretory breast cancer at a younger age in males.

Reported risk factors for breast cancer include exposure to known carcinogens, genetic and environmental factors, hormonal disorders, and gynecomastia.1,21 The relation of secretory breast cancer to these potential etiological factors remains unclear. In only 4 of 15 male patients was gynecomastia noticed. Although in the vast majority of patients with gynecomastia the estrogen receptor status is positive, the tumor was devoid of steroid-receptor staining among patients with gynecomastia and secretory breast cancer. Because estrogen and progesterone receptor status are variable in female and male secretory breast cancer patients in all age groups, the pathogenesis of this tumor type probably is not related to female sex hormones.19 Various chromosomal and molecular abnormalities associated with secretory breast carcinoma have been reported,14,22,23 but the significance of these genetic abnormalities in secretory carcinoma has yet to be determined. Coexistence with juvenile papillomatosis has been described.24

The histological and cytological features in secretory carcinoma are distinctive.20,25 Histological patterns observed include solid, microcystic, and ductal, with many neoplasms containing all three patterns. Multicentricity has been reported.20,26 The neoplastic cells are polygonal, with minimal or absent atypism and mitotic activity. Characteristic is the presence of abundant intra- and extracellular secretion of a material containing sulfated mucopolysaccharides and mucin, and a vacuolated or granular eosinophilic cytoplasm.4 Although the mucicarmine staining of this secretory material has proven somewhat variable, it always stains with Alcian blue and PAS with and without diastase.20,27 Tumor cells usually also demonstrate positive immunohistochemical staining with keratin, S-100 protein, carcinoembryonic antigen, and {alpha}-lactalbumin.9,16 Other breast lesions with secretory features that should be included in the histological differential diagnosis are cystic hypersecretory carcinoma, cystic hypersecretory hyperplasia, signet-ring-cell breast carcinoma, and lactational adenoma.20 The cytology of secretory breast carcinoma is potentially distinguishable from that of other mammary carcinoma variants, shows presence of PAS-positive intracytoplasmic globular material in malignant epithelial cells, and may resemble lactational changes.10,12,23 The DNA index at flow cytometry is reported to be diploid, with a low S-phase fraction—findings associated with a favorable prognosis on the basis of analysis of common forms of breast carcinoma.9,10,12,20,29

In this and other series, the duration of symptoms varied from less than a month to more than 20 years. Younger patients are reported to have a significantly longer interval between detection and treatment.19 That phenomenon could not be confirmed distinctively in our small series of male patients. Regardless of age and sex, secretory breast carcinoma is generally detected by palpation. The maximal tumor diameter has been reported from smaller than 1 cm to as large as 16 cm, and the tumor is usually located subareolarly.4,9 In most cases the tumors are firm, mobile, and well circumscribed. Clinically and radiologically, they often resemble fibroadenoma or fibrocystic changes. Few data are available on mammographic findings. A benign opacity, asymmetric densities, or microcalcifications might be seen.20 Sonography might demonstrate a well-defined hypoechoic nodule.16

The treatment of secretory breast carcinoma is surgical. There is little consensus, however, about the extent of surgery. A sufficient number of case reports of local recurrence suggest that local excision alone may not constitute adequate therapy, and mastectomy has been advocated as standard treatment.4,5,7,18–20,25–27,29,30 Richard et al.20 reported, in a literature review of 33 reported cases with follow-up in adult females, that 33% of patients treated by less than simple mastectomy demonstrated local recurrent disease. The alternative approach of breast-conserving surgery, excising the tumor with generous margins that will encompass any associated in situ carcinoma, may be adequate for many patients and deals with the issue of future breast development in children.

In our series of male patients, lymph node metastases were found in 3 of 10 cases in which axillary lymph nodes were histologically examined. A similar rate of nodal metastases has been reported in series of adult female and pediatric patients.8,20 Because of the increased rate of lymph node metastases, axillary lymph node dissection is advocated for tumors of >=2 cm in maximal diameter.4,20 In this series of male patients, however, two of the three patients with involved axillary lymph nodes had a tumor of <2 cm. This may indicate that in male patients, secretory breast cancer metastasizes more easily to the regional lymph nodes and that, consequently, axillary lymph node dissection is warranted in any case, in contrast to recommendations for female patients.4,20 In the era of sentinel node biopsy, unnecessary axillary lymph node dissection might be avoided in the future.31,32

Adjuvant treatment has been administered in several secretory breast cancer cases. Postoperative radiotherapy has been used on at least three occasions after simple mastectomy4,7,18 and once after modified radical mastectomy.15 After local excision of the tumor, radiotherapy was administered in two reported cases.8,26 Adjuvant chemotherapy was applied in at least three cases.4,15,30 There is insufficient evidence to date to recommend either adjuvant approach in the management of primary secretory breast cancer.

Distant metastatic disease is extremely rare. At initial diagnosis, staging did not reveal distant metastases in any patient, whereas four patients presented with distant metastases a few months to 20 years after surgery.4,7,33 Unfortunately, this tumor seems to not be responsive to chemotherapy.33

As mentioned previously, this type of breast cancer is marked by its favorable prognosis. The long period of symptoms before admission and the subsequent absence of lymph node and distant metastases at diagnosis in most cases support its indolent biological behavior. Adverse prognostic features reported are size >2 cm, lack of gross circumscription, and infiltrative margins.20 In adults, this distinct tumor type has on occasion been more aggressive in character.7 The significance of the hormone receptor status in secretory breast cancer regarding prognosis is unclear, contrary to current knowledge in common breast cancer in females.34 In our review series, recurrence with subsequent death was noted in only one case. In the remaining cases, no recurrence was observed. Moreover, it has to be mentioned that follow-up was relatively short in a number of cases, whereas outcome was undefined in three cases. Slow growth and delayed recurrence necessitate prolonged follow-up for definite conclusions.7 Recurrence has been reported 20 years after initial treatment.7 Death as a result of this malignant disease has been reported in only four cases.4,7,27,33

In conclusion, secretory breast cancer is very rare in males; only 15 such cases could be identified in the world literature, including our case. It seems to occur at a younger age in males than in females. A sufficient number of female cases have been reported with local recurrence after local excision. Although in females lymph node metastases are generally rarely observed in secretory breast carcinoma <2 cm in diameter, in male patients nodal metastases might occur more frequently in smaller tumors. Therefore, mastectomy with sentinel lymph node biopsy or axillary lymph node dissection is recommended in any male case. Although the reported follow-up period in most male cases is short, its biological behavior seems to be similarly favorable in either sex.


   Footnotes
 
Secretory breast carcinoma is a distinct form of breast cancer, occurring very rarely in males, that seems to occur at a younger age in males than in females. Mastectomy with sentinel lymph node biopsy, axillary lymph node dissection, or both are recommended in any male case. Biological behavior seems to be similarly favorable in either sex.

Received for publication January 22, 2002. Accepted for publication May 6, 2002.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Donegan WL, Redlich PN. Breast cancer in men. Surg Clin North Am 1996; 76: 343–63.[CrossRef][Medline]
  2. Visfelt J, Scheike O. Male breast cancer. I. Histologic subtyping and grading of 187 Danish cases. Cancer 1973; 32: 985–90.[CrossRef][Medline]
  3. Simpson JS, Barson AJ. Breast tumours in infants and children: a 40-year review of cases at a children’s hospital. Can Med Assoc J 1969; 101: 100–2.[Medline]
  4. Tavassolli FA, Norris HJ. Secretory carcinoma of the breast. Cancer 1980; 45: 2404–13.[CrossRef][Medline]
  5. Karl SR, Ballantine TVN, Zaino R. Juvenile secretory carcinoma of the breast. J Pediatr Surg 1985; 20: 368–71.[CrossRef][Medline]
  6. Roth JA, Discafani C, O’Malley M. Secretory breast carcinoma in a man. Am J Surg Pathol 1988; 12: 150–4.[Medline]
  7. Krausz T, Jenskins D, Grontoft O, Pollock DJ, Azoopardi JG. Secretory carcinoma of the breast in adults: emphasis on late recurrence and metastasis. Histopathology 1989; 14: 25–36.[Medline]
  8. Serour F, Gilad A, Kopolovic J, Krispin M. Secretory breast cancer in childhood and adolescence: report of a case and review of the world literature. Med Pediatr Oncol 1992; 20: 341–4.[Medline]
  9. Lamovec J, Bracko M. Secretory carcinoma of the breast: light microscopical, immunohistochemical flow cytometric study. Mod Pathol 1994; 7: 475–9.[Medline]
  10. Pohar-Marinsek Z, Golouh R. Secretory breast cancer in a man diagnosed by fine needle aspiration biopsy. Acta Cytol 1994; 38: 446–50.[Medline]
  11. Kuwabara H, Yamane M, Okada S. Secretory breast carcinoma in a 66 year old man. J Clin Pathol 1998; 51: 545–7.[Abstract]
  12. Vesoulis Z, Kashkari S. Fine needle aspiration of secretory breast carcinoma resembling lactational changes. Acta Cytol 1998; 42: 1032–6.[Medline]
  13. Kameyama K, Mukai M, Iri H, et al. Secretory carcinoma of the breast in a 51-year-old male. Pathol Int 1998; 48: 994–7.[Medline]
  14. Chevallier A, Boissy C, Rampal A, et al. Le carcinome secretoire du sein. A propos d’une observation chez un garcon de 9 ans. Clin Exp Pathol 1999; 47: 88–91.[Medline]
  15. Yildirim E, Turhan N, Pak I, Berberoglu U. Secretory breast carcinoma in a boy. Eur J Surg Oncol 1999; 25: 98–9.[Medline]
  16. Bhagwandeen BS, Fenton L. Secretory carcinoma of the breast in a 9-year-old boy. Pathology 1999; 31: 166–8.[CrossRef][Medline]
  17. Titus J, Sillar RW, Fenton LE. Secretory breast carcinoma in a 9-year-old boy. Aust N Z J Surg 2000; 70: 144–6.[CrossRef][Medline]
  18. McDivitt W, Stewart FW. Breast carcinoma in children. JAMA 1966; 195: 144–6.
  19. Rosen PP, Cranor ML. Secretory carcinoma of the breast. Arch Pathol Lab Med 1991; 115: 141–4.[Medline]
  20. Richard G, Hawk JCIII, Baker AS Jr, Austin RM. Multicentric adult secretory breast carcinoma: DNA flow cytometric findings, prognostic features, and review of the world literature. J Surg Oncol 1990; 44: 238–44.[Medline]
  21. Sasco AJ, Lowenfels AB, Pasker-de Jong P. Review article: epidemiology of male breast cancer—a meta-analysis of published case-control studies and discussion of selected aetiological factors. Int J Cancer 1993; 53: 538–49.[Medline]
  22. Maitra A, Tavassoli FA, Albores-Saavedra J, et al. Molecular abnormalities associated with secretory carcinomas of the breast. Hum Pathol 1999; 30: 1435–40.[CrossRef][Medline]
  23. Murphy JJ, Morzaria S, Gow KW, Magee JF. Breast cancer in a 6-year-old child. J Pediatr Surg 2000; 35: 765–7.[CrossRef][Medline]
  24. Nonomura A, Kimura A, Mizukami Y, et al. Secretory carcinoma of the breast associated with juvenile papillomatosis in a 12-year-old girl. Acta Cytol 1995; 39: 569–76.[Medline]
  25. Akthar M, Robinson C, Ali MA, Godwin J. Secretory carcinoma of the breast in adults. Light and electron microscopic study of three cases and review of the literature. Cancer 1983; 51: 2404–13.
  26. Tournemaine N, Audoiin AF, Anguill C, Gordeeff S. Le carcinome secretoire juvenile: cinq nouveaus cas chez des femmes d’age adulte. Arch Anat Cytol Pathol 1986; 34: 146–51.[Medline]
  27. Nguyen G, Neifer R. Aspiration biopsy cytology of secretory carcinoma of the breast. Diagn Cytopathol 1987; 3: 234–7.[Medline]
  28. Gupta RK, Kenwright D, Narran S, Lallu S, Fauck R. Fine needle aspiration cytodiagnosis of secretory carcinoma of the breast. Cytopathology 2000; 11: 496–502.[CrossRef][Medline]
  29. Mies C. Recurrent secretory carcinoma in residual mammary tissue after mastectomy. Am J Surg Pathol 1993; 17: 715–21.[CrossRef][Medline]
  30. Sullivan JJ, Magee HR, Donald KJ. Secretory (juvenile) carcinoma of the breast. Pathology 1977; 9: 341–6.[Medline]
  31. Sanidas EE, Tsiftsis DD. Technical details for the sentinel node biopsy in breast cancer: a guide for the training process. Eur J Surg Oncol 2001; 27: 414–27.[CrossRef][Medline]
  32. Port ER, Fey JV, Cody HSIII, Borgen PI. Sentinel node biopsy in patients with male breast carcinoma. Cancer 2001; 91: 319–23.[CrossRef][Medline]
  33. Herz H, Cooke B, Goldstein D. Metastatic secretory breast cancer. Non-responsiveness to chemotherapy: case report and review of the literature. Ann Oncol 2000; 11: 1343–7.[Abstract/Free Full Text]
  34. Osborne CK. Steroid hormone receptors in breast cancer management. Breast Cancer Res Treat 1998; 51: 227–3.[CrossRef][Medline]



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