Clinicopathologic challenge
Flesh-colored papule on the areola Darya P. Shlapak1, MBA, Justin R. Sigmon2, MD, Daniel J. Sheehan1, MD, and Loretta S. Davis1, MD
1 University of Mississippi Medical Center, Jackson, MS, USA, and 2Division of Dermatology, Georgia Health Sciences University, Augusta, GA, USA
What is your diagnosis?
Correspondence Justin R. Sigmon, MD Georgia Health Sciences University Division of Dermatology 1004 Chafee Avenue, FH-100 Augusta, GA 30912-3155 USA E-mail: [email protected] Conflicts of interest: None.
Case history An 18-year-old healthy woman presented with a 2-year history of a small papule on her left areola, which had been gradually increasing in size. She reported an occasional white, milky discharge and crusting with mild irritation from rubbing against her clothing. She denied tenderness, pruritus, or having tried anything to treat the papule. Family history was negative for breast cancer. Physical examination revealed a non-tender 3 mm flesh-colored papule with mild erythema on the left areola (Fig. 1).
Figure 1 Flesh-colored papule on the left areola ª 2013 The International Society of Dermatology
Figure 2 Hematoxylin and eosin, 940. Well-circumscribed unencapsulated dermal and subcutaneous lobular proliferation of cystic, slightly dilated branching tubular structures
Figure 3 Hematoxylin and eosin, 9100. Epithelial cells demonstrating eosinophilic cytoplasm and basally displaced nuclei. Myoepithelial cell layer is seen. Duct-like structures containing typical apocrine epithelial cells with decapitation secretion can be appreciated International Journal of Dermatology 2013, 52, 1297–1299
1297
1298
Clinicopathologic challenge
Shlapak et al.
Flesh-colored papule on the areola
Diagnosis Tubular apocrine adenoma (TAA) of the breast. Discussion TAA is an uncommon benign sweat gland neoplasm first described by Landry and Winkelmann in 1972.1 TAA has a predilection for the scalp but has been reported on the eyelid, external auditory meatus, cheek, axilla, nose, chest, back, calf, trunk, perianal region, and vulva.2–13 Rare pediatric cases have been reported, including a lesion on the vaginal introitus of an 8-year-old.14 TAA of the breast is rare, especially in pediatric and adolescent patients.15 Clinically, TAA commonly presents as a well-defined, mobile, solitary nodule, usually without ulceration, crusting, or erythema. Although present in our case, a milky discharge is not typically reported. The clinical differential includes nipple adenoma (NA), syringocystadenoma papilliferum (SCAP), Montgomery tubercle (MT), papillary eccrine adenoma (PEA), papillary apocrine carcinoma (PAC), Paget’s disease of the breast, and breast carcinoma. Many of these entities can closely resemble TAA, making a biopsy and histological examination necessary for diagnosis. Young age and the lack of a family history of breast carcinoma favor a benign neoplasm such as TAA, NA, SCAP, MT, or PEA. NA (also known as erosive adenomatosis or florid papillomatosis) is usually located within or directly overlying the nipple and often presents with characteristic crusting, erythema, discharge, and tenderness in contrast to TAA, which is usually asymptomatic and does not typically occur on or within the nipple.16,17 SCAP, like TAA of the breast, is extremely rare, and when it does not arise in a nevus sebaceous, it may be clinically indistinguishable from TAA. Multiple grouped papules, verrucous or papillary plaques, and vesicle-like inclusions with umbilication are more characteristic of SCAP.16,18 MTs can clinically present similarly to TAA, especially if large and very prominent. However, MTs represent the orifices of normal sebaceous glands and are usually asymptomatic, evenly distributed on both breasts, and easily differentiated by histology.19,20 PEA is considered by many to be a variant of TAA, which usually favors sites atypical for TAA such as the dorsal hand or foot.21 Routine histopathological examination of TAA usually demonstrates a characteristic well-circumscribed unencapsulated dermal and subcutaneous lobular proliferation of cystic, non-dilated or slightly dilated branching tubular structures lined by two or more layers of cells (Fig. 2). These cells most often have an eosinophilic cytoplasm and basally displaced nuclei in addition to a peripherally located myoepithelial cell layer. Intraluminal papillary International Journal of Dermatology 2013, 52, 1297–1299
projections can sometimes be seen. The tubular arrangement is connected to the epidermis by single or multiple duct-like structures and contains typical apocrine epithelial cells with decapitation secretion (Fig. 3). Immunohistochemically, these cells may contain periodic acid Schiffpositive diastase-resistant granules and iron pigment. The luminal cells are immunoreactive to carcinoembryonic antigen and epithelial membrane antigen. The secretory cells are positive for low molecular weight keratin, and the glandular epithelium often expresses gross cystic disease fluid protein 15. Peripheral cells are usually positive for S100 protein.22,23 The histological differential of TAA mainly includes its close counterpart PEA as well as SCAP and PAC. A dense fibrous stroma with a pauci-inflammatory infiltrate helps differentiate TAA from SCAP, which contains fibrovascular cores infiltrated by numerous plasma cells and more prominent tubular dilatation.2,23 Interestingly, several case reports have described TAA and SCAP occurring together, including a case of both being present within a nevus sebaceous.3,8,9 TAA may be differentiated from PEA by the presence of prominent apocrine decapitation secretion, especially if correlated with the typical location of TAA on the scalp or within a nevus sebaceous; however, it may be difficult to make the distinction. TAA is distinguished from PAC by the absence of cytological atypia and lack of mitoses or an infiltrative growth pattern.21,24 Although benign and not shown to have malignant potential, TAA can be locally aggressive and thus may clinically be mistaken for primary or metastatic adenocarcinoma. Thus, diagnostic skin biopsy is essential when evaluating neoplasms of the nipple–areolar complex in women of any age. In cases of TAA, complete surgical excision with clear margins is recommended, as recurrences have been reported.13,22 Not surprisingly, our patient chose observation and close follow-up rather than additional surgery, as she was concerned about the aesthetic appearance of her breast. References 1 Landry M, Winkelmann RK. An unusual tubular apocrine adenoma. Arch Dermatol 1972; 105: 869–879. 2 Stokes J, Ironside J, Smith C, et al. Tubular apocrine adenoma-an unusual eyelid tumour. Eye 2005; 19: 237– 239. 3 Lee CK, Jang KT, Cho YS. Tubular apocrine adenoma with syringocystadenoma papilliferum arising from the external auditory canal. J Laryngol Otol 2005; 119: 1004–1006. 4 Martinelli PT, Cohen PR, Schulze KE, et al. Mohs micrographic surgery for tubular apocrine adenoma. Int J Dermatol 2006; 45: 1377–1378. ª 2013 The International Society of Dermatology
Shlapak et al.
5 Amo Y, Kawano N. A case of ductal apocrine carcinoma in the left axilla with tubular apocrine adenoma in the right axilla. J Dermatol 2003; 30: 72–75. 6 Mitsuishi T, Kawana S. Tubular apocrine adenoma of the nose. Eur J Dermatol 2011; 21: 132. 7 Epstein BA, Argenyi ZB, Goldstein G, et al. An unusual presentation of a congenital benign apocrine hamartoma. J Cutan Pathol 1990; 17: 53–58. 8 Lee HJ, Cho E, Kim MH, et al. Syringocystadenoma papilliferum of the back combined with a tubular apocrine adenoma. Ann Dermatol 2011; 23: 151–154. 9 Ahn BK, Park YK, Kim YC. A case of tubular apocrine adenoma with syringocystadenoma papilliferum arising in nevus sebaceous. J Dermatol 2004; 31: 508–510. 10 Yoon JH, Ahn HH, Kye YC, et al. Syringocystadenoma papilliferum in co-existence with tubular apocrine adenoma on the calf. Ann Dermatol 2011; 23: 175–178. 11 Nakagomi D, Harada K, Shimada S. Case of tubular apocrine adenoma with follicular differentiation located on the trunk. J Dermatol 2012; 39: 653–654. 12 MacNeill KN, Riddell RH, Ghazarian D. Perianal apocrine adenocarcinoma arising in a benign apocrine adenoma; first case report and review of literature. J Clin Pathol 2005; 58: 217–219. 13 El Demellawy D, Daya D, Alowami S. Vulvar apocrine tubular adenoma: an unusual location. Int J Gynecol Pathol 2008; 27: 301–303. 14 Ross I, Shwayder T. Tubular apocrine adenoma: presentation in the vaginal introitus of an eight-year-old. Pediatr Dermatol 2010; 27: 200–201. 15 Cashell AW. Apocrine adenoma of the breast. W V Med J 2008; 104: 16–19.
ª 2013 The International Society of Dermatology
Flesh-colored papule on the areola
Clinicopathologic challenge
16 Cosechen MS, Wojcik AS, Piva FM, et al. Erosive adenomatosis of the nipple. An Bras Dermatol 2011; 86: 17–20. 17 Boutayeb S, Benomar S, Sbitti Y, et al. Nipple adenoma in a man: an unusual case report. Int J Surg Case Rep 2012; 3: 190–192. 18 Vaos G, Pierrakou P. Syringocystadenoma papilliferum: a rare breast tumor in a young boy. Pediatr Dev Pathol 2006; 9: 381–383. 19 Watkins F, Giacomantonio M, Salisbury S. Nipple discharge and breast lump related to Montgomerys tubercles in adolescent females. J Pediatr Surg 1988; 23: 718–720. 20 Collins LC, Schnitt SJ. Breast. In: Mills SE, ed. Histology for Pathologists, 3rd edn. Philadelphia, PA: Lippincott Williams & Wilkins, 2004: 66 [WWW document]. URL http://flylib.com/books/en/2.953.1.9/1/ [accessed on 31 August 2012]. 21 Elston DM, Ferringer T, Ko CJ, et al. Dermatopathology: Requisites in Dermatology, 1st edn. Philadelphia, PA: Elsevier, 2009: 101. 22 James WD, Berger TG, Elston DM. Epidermal nevi, neoplasms, and cysts. In: James WD, Berger TG, Elston DM, eds. Andrew’s Diseases of the Skin: Clinical Dermatology, 11th edn. Philadelphia, PA: Elsevier, 2011: 658. 23 Obaidat NA, Alsaad KO, Ghazarian D. Skin adnexal neoplasms-part 2: an approach to tumours of cutaneous sweat glands. J Clin Pathol 2007; 60: 145–159. 24 McKee PH, Calonje E, Brenn T, et al. McKee’s Pathology of the Skin, 4th edn. China: Elsevier, 2012: 1513–1514.
International Journal of Dermatology 2013, 52, 1297–1299
1299
Flesh-colored papule on the areola Darya P. Shlapak1, MBA, Justin R. Sigmon2, MD, Daniel J. Sheehan1, MD, and Loretta S. Davis1, MD
1 University of Mississippi Medical Center, Jackson, MS, USA, and 2Division of Dermatology, Georgia Health Sciences University, Augusta, GA, USA
What is your diagnosis?
Correspondence Justin R. Sigmon, MD Georgia Health Sciences University Division of Dermatology 1004 Chafee Avenue, FH-100 Augusta, GA 30912-3155 USA E-mail: [email protected] Conflicts of interest: None.
Case history An 18-year-old healthy woman presented with a 2-year history of a small papule on her left areola, which had been gradually increasing in size. She reported an occasional white, milky discharge and crusting with mild irritation from rubbing against her clothing. She denied tenderness, pruritus, or having tried anything to treat the papule. Family history was negative for breast cancer. Physical examination revealed a non-tender 3 mm flesh-colored papule with mild erythema on the left areola (Fig. 1).
Figure 1 Flesh-colored papule on the left areola ª 2013 The International Society of Dermatology
Figure 2 Hematoxylin and eosin, 940. Well-circumscribed unencapsulated dermal and subcutaneous lobular proliferation of cystic, slightly dilated branching tubular structures
Figure 3 Hematoxylin and eosin, 9100. Epithelial cells demonstrating eosinophilic cytoplasm and basally displaced nuclei. Myoepithelial cell layer is seen. Duct-like structures containing typical apocrine epithelial cells with decapitation secretion can be appreciated International Journal of Dermatology 2013, 52, 1297–1299
1297
1298
Clinicopathologic challenge
Shlapak et al.
Flesh-colored papule on the areola
Diagnosis Tubular apocrine adenoma (TAA) of the breast. Discussion TAA is an uncommon benign sweat gland neoplasm first described by Landry and Winkelmann in 1972.1 TAA has a predilection for the scalp but has been reported on the eyelid, external auditory meatus, cheek, axilla, nose, chest, back, calf, trunk, perianal region, and vulva.2–13 Rare pediatric cases have been reported, including a lesion on the vaginal introitus of an 8-year-old.14 TAA of the breast is rare, especially in pediatric and adolescent patients.15 Clinically, TAA commonly presents as a well-defined, mobile, solitary nodule, usually without ulceration, crusting, or erythema. Although present in our case, a milky discharge is not typically reported. The clinical differential includes nipple adenoma (NA), syringocystadenoma papilliferum (SCAP), Montgomery tubercle (MT), papillary eccrine adenoma (PEA), papillary apocrine carcinoma (PAC), Paget’s disease of the breast, and breast carcinoma. Many of these entities can closely resemble TAA, making a biopsy and histological examination necessary for diagnosis. Young age and the lack of a family history of breast carcinoma favor a benign neoplasm such as TAA, NA, SCAP, MT, or PEA. NA (also known as erosive adenomatosis or florid papillomatosis) is usually located within or directly overlying the nipple and often presents with characteristic crusting, erythema, discharge, and tenderness in contrast to TAA, which is usually asymptomatic and does not typically occur on or within the nipple.16,17 SCAP, like TAA of the breast, is extremely rare, and when it does not arise in a nevus sebaceous, it may be clinically indistinguishable from TAA. Multiple grouped papules, verrucous or papillary plaques, and vesicle-like inclusions with umbilication are more characteristic of SCAP.16,18 MTs can clinically present similarly to TAA, especially if large and very prominent. However, MTs represent the orifices of normal sebaceous glands and are usually asymptomatic, evenly distributed on both breasts, and easily differentiated by histology.19,20 PEA is considered by many to be a variant of TAA, which usually favors sites atypical for TAA such as the dorsal hand or foot.21 Routine histopathological examination of TAA usually demonstrates a characteristic well-circumscribed unencapsulated dermal and subcutaneous lobular proliferation of cystic, non-dilated or slightly dilated branching tubular structures lined by two or more layers of cells (Fig. 2). These cells most often have an eosinophilic cytoplasm and basally displaced nuclei in addition to a peripherally located myoepithelial cell layer. Intraluminal papillary International Journal of Dermatology 2013, 52, 1297–1299
projections can sometimes be seen. The tubular arrangement is connected to the epidermis by single or multiple duct-like structures and contains typical apocrine epithelial cells with decapitation secretion (Fig. 3). Immunohistochemically, these cells may contain periodic acid Schiffpositive diastase-resistant granules and iron pigment. The luminal cells are immunoreactive to carcinoembryonic antigen and epithelial membrane antigen. The secretory cells are positive for low molecular weight keratin, and the glandular epithelium often expresses gross cystic disease fluid protein 15. Peripheral cells are usually positive for S100 protein.22,23 The histological differential of TAA mainly includes its close counterpart PEA as well as SCAP and PAC. A dense fibrous stroma with a pauci-inflammatory infiltrate helps differentiate TAA from SCAP, which contains fibrovascular cores infiltrated by numerous plasma cells and more prominent tubular dilatation.2,23 Interestingly, several case reports have described TAA and SCAP occurring together, including a case of both being present within a nevus sebaceous.3,8,9 TAA may be differentiated from PEA by the presence of prominent apocrine decapitation secretion, especially if correlated with the typical location of TAA on the scalp or within a nevus sebaceous; however, it may be difficult to make the distinction. TAA is distinguished from PAC by the absence of cytological atypia and lack of mitoses or an infiltrative growth pattern.21,24 Although benign and not shown to have malignant potential, TAA can be locally aggressive and thus may clinically be mistaken for primary or metastatic adenocarcinoma. Thus, diagnostic skin biopsy is essential when evaluating neoplasms of the nipple–areolar complex in women of any age. In cases of TAA, complete surgical excision with clear margins is recommended, as recurrences have been reported.13,22 Not surprisingly, our patient chose observation and close follow-up rather than additional surgery, as she was concerned about the aesthetic appearance of her breast. References 1 Landry M, Winkelmann RK. An unusual tubular apocrine adenoma. Arch Dermatol 1972; 105: 869–879. 2 Stokes J, Ironside J, Smith C, et al. Tubular apocrine adenoma-an unusual eyelid tumour. Eye 2005; 19: 237– 239. 3 Lee CK, Jang KT, Cho YS. Tubular apocrine adenoma with syringocystadenoma papilliferum arising from the external auditory canal. J Laryngol Otol 2005; 119: 1004–1006. 4 Martinelli PT, Cohen PR, Schulze KE, et al. Mohs micrographic surgery for tubular apocrine adenoma. Int J Dermatol 2006; 45: 1377–1378. ª 2013 The International Society of Dermatology
Shlapak et al.
5 Amo Y, Kawano N. A case of ductal apocrine carcinoma in the left axilla with tubular apocrine adenoma in the right axilla. J Dermatol 2003; 30: 72–75. 6 Mitsuishi T, Kawana S. Tubular apocrine adenoma of the nose. Eur J Dermatol 2011; 21: 132. 7 Epstein BA, Argenyi ZB, Goldstein G, et al. An unusual presentation of a congenital benign apocrine hamartoma. J Cutan Pathol 1990; 17: 53–58. 8 Lee HJ, Cho E, Kim MH, et al. Syringocystadenoma papilliferum of the back combined with a tubular apocrine adenoma. Ann Dermatol 2011; 23: 151–154. 9 Ahn BK, Park YK, Kim YC. A case of tubular apocrine adenoma with syringocystadenoma papilliferum arising in nevus sebaceous. J Dermatol 2004; 31: 508–510. 10 Yoon JH, Ahn HH, Kye YC, et al. Syringocystadenoma papilliferum in co-existence with tubular apocrine adenoma on the calf. Ann Dermatol 2011; 23: 175–178. 11 Nakagomi D, Harada K, Shimada S. Case of tubular apocrine adenoma with follicular differentiation located on the trunk. J Dermatol 2012; 39: 653–654. 12 MacNeill KN, Riddell RH, Ghazarian D. Perianal apocrine adenocarcinoma arising in a benign apocrine adenoma; first case report and review of literature. J Clin Pathol 2005; 58: 217–219. 13 El Demellawy D, Daya D, Alowami S. Vulvar apocrine tubular adenoma: an unusual location. Int J Gynecol Pathol 2008; 27: 301–303. 14 Ross I, Shwayder T. Tubular apocrine adenoma: presentation in the vaginal introitus of an eight-year-old. Pediatr Dermatol 2010; 27: 200–201. 15 Cashell AW. Apocrine adenoma of the breast. W V Med J 2008; 104: 16–19.
ª 2013 The International Society of Dermatology
Flesh-colored papule on the areola
Clinicopathologic challenge
16 Cosechen MS, Wojcik AS, Piva FM, et al. Erosive adenomatosis of the nipple. An Bras Dermatol 2011; 86: 17–20. 17 Boutayeb S, Benomar S, Sbitti Y, et al. Nipple adenoma in a man: an unusual case report. Int J Surg Case Rep 2012; 3: 190–192. 18 Vaos G, Pierrakou P. Syringocystadenoma papilliferum: a rare breast tumor in a young boy. Pediatr Dev Pathol 2006; 9: 381–383. 19 Watkins F, Giacomantonio M, Salisbury S. Nipple discharge and breast lump related to Montgomerys tubercles in adolescent females. J Pediatr Surg 1988; 23: 718–720. 20 Collins LC, Schnitt SJ. Breast. In: Mills SE, ed. Histology for Pathologists, 3rd edn. Philadelphia, PA: Lippincott Williams & Wilkins, 2004: 66 [WWW document]. URL http://flylib.com/books/en/2.953.1.9/1/ [accessed on 31 August 2012]. 21 Elston DM, Ferringer T, Ko CJ, et al. Dermatopathology: Requisites in Dermatology, 1st edn. Philadelphia, PA: Elsevier, 2009: 101. 22 James WD, Berger TG, Elston DM. Epidermal nevi, neoplasms, and cysts. In: James WD, Berger TG, Elston DM, eds. Andrew’s Diseases of the Skin: Clinical Dermatology, 11th edn. Philadelphia, PA: Elsevier, 2011: 658. 23 Obaidat NA, Alsaad KO, Ghazarian D. Skin adnexal neoplasms-part 2: an approach to tumours of cutaneous sweat glands. J Clin Pathol 2007; 60: 145–159. 24 McKee PH, Calonje E, Brenn T, et al. McKee’s Pathology of the Skin, 4th edn. China: Elsevier, 2012: 1513–1514.
International Journal of Dermatology 2013, 52, 1297–1299
1299
![[Pink papule on the temple].](/assets/img/hold.png)
