Clinical Review & Education
JAMA Dermatology Clinicopathological Challenge
Subareolar Nodule With Calcifications on Screening Mammography Corey M. DeWitt, BA; Jose E. Peraza, MD; Daniel M. Peraza, MD
A
B
C
Figure. A, Firm, irregular, subareolar nodule of left nipple measuring 2 cm in diameter. B, Mammography of the left breast. C, Biopsy specimen of the subareolar nodule (hematoxylin-eosin, original magnification ×20).
A healthy 60-year-old woman presented with a painless subareolar nodule of her left nipple measuring 2 cm in diameter (Figure, A) that had been present for several months. Screening mammography (Figure, B) performed 4 weeks prior revealed a large grouping of left breast subareolar calcificaQuiz at jamadermatology.com tions extending into the skin and nipple. Follow-up ultrasonography demonstrated no discrete abnormal mass or shadowing but did show multiple echogenic foci consistent with findings on mammography. An incisional biopsy specimen of the mass was obtained and sent for histopathologic evaluation (Figure, C).
jamadermatology.com
WHAT IS THE DIAGNOSIS?
A. Tubular carcinoma B. Syringomatous adenoma of the nipple C. Low-grade adenosquamous carcinoma D. Florid papillomatosis of the nipple
(Reprinted) JAMA Dermatology February 2015 Volume 151, Number 2
Copyright 2015 American Medical Association. All rights reserved.
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227
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis B. Syringomatous adenoma of the nipple
Microscopic Findings and Clinical Course Histopathologic examination revealed a dermal tumor composed of angulated glands and nests and cords of cells permeating between the muscle bundles of the nipple stroma. There was no perineural growth identified. The neoplastic cells were arranged in 2 layers and exhibited minimal nuclear pleomorphism and scant cytoplasm. The stroma was fibrotic without calcification and keratinous cysts were present. The deepest portion of the tumor was measured to be 3.3 mm below the stratum corneum. Once the results from the histopathologic evaluation were obtained, the patient returned to the clinic and was advised to undergo complete tumor excision.
Discussion Syringomatous adenoma of the nipple (SAN) is a benign, locally infiltrating neoplasm with similar morphology to tumors of eccrine duct origin.1 Despite its benign behavior, SAN is often misdiagnosed as tubular carcinoma or low-grade adenosquamous carcinoma (LGAC) of the breast owing to similarities in clinical presentation and findings on mammography. Syringomatous adenoma of the nipple typically presents as a 1- to 3-cm unilateral firm mass in the nipple or subareolar region of the breast. Symptoms may include pain, crusting, itchiness, nipple discharge, and/or nipple inversion. All but 2 reported cases of SAN have occurred in women, between the ages of 11 to 76 years.1,2 Radiographic findings of SAN are indistinguishable from carcinoma. Mammography often demonstrates a dense, irregular mass with foci of microcalcifications in the subareolar region, findings that are highly suspicious for malignancy.3 Definitive diagnosis requires a biopsy of the tumor and microscopic evaluation. Histopathologic criteria to diagnose SAN include (1) location in dermis and subcutaneous tissue of nipple or areola; (2) irregular, compressed, or comma-shaped tubules infiltrating into smooth muscle and/or nerves; (3) myoepithelial cells around the tubules; (4) cysts filled with keratinous material and lined by stratified squamous epithelium; and (5) no mitotic activity and necrosis.1 Despite these criteria, it remains difficult to distinguish SAN from tubular carcinoma, florid papillomatosis of the nipple (a variant of intraductal papilloma), or LGAC of the breast microscopically because of several common features, but there are certain characteristics unique to each allowing for their differentiation. Florid papillomatosis of the nipple, for instance, typically displays epitheARTICLE INFORMATION Author Affiliations: Geisel School of Medicine at Dartmouth, West Lebanon, New Hampshire. Corresponding Author: Corey M. DeWitt, BA, Geisel School of Medicine at Dartmouth, 52 Sachem Cir, West Lebanon, NH 03784 (corey.m.dewitt.med @dartmouth.edu). Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. Published Online: November 12, 2014. doi:10.1001/jamadermatol.2014.2709. Conflict of Interest Disclosures: None reported.
228
lial hyperplasia originating from lactiferous ducts, which causes displacement of the nipple stroma rather than the infiltrative pattern seen in SAN.1 Tubular carcinoma and SAN can show similar patterns of infiltration. However, the presence of squamous metaplasia and mitotic figures, in addition to the absence of myoepithelial cells, help differentiate tubular carcinoma from SAN.1 Although immunohistochemical stains were not used in our patient, they can be useful in differentiating difficult cases of tubular carcinoma. Smooth muscle myosin heavy chain and p63 proteins are frequently used to label and identify myoepithelial cells. Their absence in a specimen further suggests a diagnosis of tubular carcinoma rather than SAN. In addition, the anatomic location of tubular carcinoma is not typically confined to the nipple-areola region, as is the case in our patient.4 The differentiation between LGAC and SAN can be subtle owing to the amount of common features on clinical and pathologic examination. However, it remains vitally important to distinguish these 2 lesions due to their difference in metastatic potential. Low-grade adenosquamous carcinoma has a small but well-known potential to metastasize, whereas SAN does not.4 Microscopically, SAN is distinguished from LGAC by its characteristic progression from cysts to small ductules to cords and nests of cells. In addition, LGAC frequently demonstrates a prevalence of squamous differentiation, whereas this is a lesser component of SAN.4 Another primary skin tumor confused histologically for SAN is microcystic adnexal carcinoma (MAC). Some consider MACs and SANs to be the same neoplastic entity; however, their clinical behavior is drastically different. Again, there have been no reported cases of metastatic SAN, whereas MACs have shown metastatic potential in various case reports.5-7 In addition, MACs frequently show recurrence after conservative excision, while only a small number of SANs have recurred.4 Despite this difference in clinical behavior, definitive treatment remains the same for both. Treatment of SAN requires complete excision of the mass. There have been no reported cases of recurrence after achievement of negative margins with excision.1 However, those with positive margins on excision demonstrate a high rate of recurrence during a 1- to 6-year follow-up.4 Recurrences are typically managed with local reexcision. In conclusion, SAN is a benign, locally aggressive tumor of the breast that must be considered in any patient who presents with an areolar mass and suggestive findings on mammography. Identification of this benign process is critical to avoid misdiagnosis and subsequent unnecessary surgery and psychological stress.
Additional Contributions: Dorothea Barton, MD, Dartmouth-Hitchcock Medical Center, prepared the histopathologic photographs. No financial compensation was provided.
4. Page RN, Dittrich L, King R, Boulos F, Page DL. Syringomatous adenoma of the nipple occurring within a supernumerary breast: a case report. J Cutan Pathol. 2009;36(11):1206-1209.
REFERENCES
5. Bier-Laning CM, Hom DB, Gapany M, Manivel JC, Duvall AJ III. Microcystic adnexal carcinoma. Laryngoscope. 1995;105(11):1197-1201.
1. Oo KZ, Xiao PQ. Infiltrating syringomatous adenoma of the nipple. Arch Pathol Lab Med. 2009; 133(9):1487-1489. 2. Carter E, Dyess DL. Infiltrating syringomatous adenoma of the nipple: a case report and 20-year retrospective review. Breast J. 2004;10(5):443-447. 3. Coulthard A, Liston J, Young JR. Case report: infiltrating syringomatous adenoma of the breast—appearances on mammography and ultrasonography. Clin Radiol. 1993;47(1):62-64.
6. Carroll P, Goldstein GD, Brown CW Jr. Metastatic microcystic adnexal carcinoma in an immunocompromised patient. Dermatol Surg. 2000;26(6):531-534. 7. Ohta M, Hiramoto M, Ohtsuka H. Metastatic microcystic adnexal carcinoma: an autopsy case. Dermatol Surg. 2004;30(6):957-960.
JAMA Dermatology February 2015 Volume 151, Number 2 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Georgetown University Medical Center User on 05/22/2015
jamadermatology.com
JAMA Dermatology Clinicopathological Challenge
Subareolar Nodule With Calcifications on Screening Mammography Corey M. DeWitt, BA; Jose E. Peraza, MD; Daniel M. Peraza, MD
A
B
C
Figure. A, Firm, irregular, subareolar nodule of left nipple measuring 2 cm in diameter. B, Mammography of the left breast. C, Biopsy specimen of the subareolar nodule (hematoxylin-eosin, original magnification ×20).
A healthy 60-year-old woman presented with a painless subareolar nodule of her left nipple measuring 2 cm in diameter (Figure, A) that had been present for several months. Screening mammography (Figure, B) performed 4 weeks prior revealed a large grouping of left breast subareolar calcificaQuiz at jamadermatology.com tions extending into the skin and nipple. Follow-up ultrasonography demonstrated no discrete abnormal mass or shadowing but did show multiple echogenic foci consistent with findings on mammography. An incisional biopsy specimen of the mass was obtained and sent for histopathologic evaluation (Figure, C).
jamadermatology.com
WHAT IS THE DIAGNOSIS?
A. Tubular carcinoma B. Syringomatous adenoma of the nipple C. Low-grade adenosquamous carcinoma D. Florid papillomatosis of the nipple
(Reprinted) JAMA Dermatology February 2015 Volume 151, Number 2
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Georgetown University Medical Center User on 05/22/2015
227
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis B. Syringomatous adenoma of the nipple
Microscopic Findings and Clinical Course Histopathologic examination revealed a dermal tumor composed of angulated glands and nests and cords of cells permeating between the muscle bundles of the nipple stroma. There was no perineural growth identified. The neoplastic cells were arranged in 2 layers and exhibited minimal nuclear pleomorphism and scant cytoplasm. The stroma was fibrotic without calcification and keratinous cysts were present. The deepest portion of the tumor was measured to be 3.3 mm below the stratum corneum. Once the results from the histopathologic evaluation were obtained, the patient returned to the clinic and was advised to undergo complete tumor excision.
Discussion Syringomatous adenoma of the nipple (SAN) is a benign, locally infiltrating neoplasm with similar morphology to tumors of eccrine duct origin.1 Despite its benign behavior, SAN is often misdiagnosed as tubular carcinoma or low-grade adenosquamous carcinoma (LGAC) of the breast owing to similarities in clinical presentation and findings on mammography. Syringomatous adenoma of the nipple typically presents as a 1- to 3-cm unilateral firm mass in the nipple or subareolar region of the breast. Symptoms may include pain, crusting, itchiness, nipple discharge, and/or nipple inversion. All but 2 reported cases of SAN have occurred in women, between the ages of 11 to 76 years.1,2 Radiographic findings of SAN are indistinguishable from carcinoma. Mammography often demonstrates a dense, irregular mass with foci of microcalcifications in the subareolar region, findings that are highly suspicious for malignancy.3 Definitive diagnosis requires a biopsy of the tumor and microscopic evaluation. Histopathologic criteria to diagnose SAN include (1) location in dermis and subcutaneous tissue of nipple or areola; (2) irregular, compressed, or comma-shaped tubules infiltrating into smooth muscle and/or nerves; (3) myoepithelial cells around the tubules; (4) cysts filled with keratinous material and lined by stratified squamous epithelium; and (5) no mitotic activity and necrosis.1 Despite these criteria, it remains difficult to distinguish SAN from tubular carcinoma, florid papillomatosis of the nipple (a variant of intraductal papilloma), or LGAC of the breast microscopically because of several common features, but there are certain characteristics unique to each allowing for their differentiation. Florid papillomatosis of the nipple, for instance, typically displays epitheARTICLE INFORMATION Author Affiliations: Geisel School of Medicine at Dartmouth, West Lebanon, New Hampshire. Corresponding Author: Corey M. DeWitt, BA, Geisel School of Medicine at Dartmouth, 52 Sachem Cir, West Lebanon, NH 03784 (corey.m.dewitt.med @dartmouth.edu). Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. Published Online: November 12, 2014. doi:10.1001/jamadermatol.2014.2709. Conflict of Interest Disclosures: None reported.
228
lial hyperplasia originating from lactiferous ducts, which causes displacement of the nipple stroma rather than the infiltrative pattern seen in SAN.1 Tubular carcinoma and SAN can show similar patterns of infiltration. However, the presence of squamous metaplasia and mitotic figures, in addition to the absence of myoepithelial cells, help differentiate tubular carcinoma from SAN.1 Although immunohistochemical stains were not used in our patient, they can be useful in differentiating difficult cases of tubular carcinoma. Smooth muscle myosin heavy chain and p63 proteins are frequently used to label and identify myoepithelial cells. Their absence in a specimen further suggests a diagnosis of tubular carcinoma rather than SAN. In addition, the anatomic location of tubular carcinoma is not typically confined to the nipple-areola region, as is the case in our patient.4 The differentiation between LGAC and SAN can be subtle owing to the amount of common features on clinical and pathologic examination. However, it remains vitally important to distinguish these 2 lesions due to their difference in metastatic potential. Low-grade adenosquamous carcinoma has a small but well-known potential to metastasize, whereas SAN does not.4 Microscopically, SAN is distinguished from LGAC by its characteristic progression from cysts to small ductules to cords and nests of cells. In addition, LGAC frequently demonstrates a prevalence of squamous differentiation, whereas this is a lesser component of SAN.4 Another primary skin tumor confused histologically for SAN is microcystic adnexal carcinoma (MAC). Some consider MACs and SANs to be the same neoplastic entity; however, their clinical behavior is drastically different. Again, there have been no reported cases of metastatic SAN, whereas MACs have shown metastatic potential in various case reports.5-7 In addition, MACs frequently show recurrence after conservative excision, while only a small number of SANs have recurred.4 Despite this difference in clinical behavior, definitive treatment remains the same for both. Treatment of SAN requires complete excision of the mass. There have been no reported cases of recurrence after achievement of negative margins with excision.1 However, those with positive margins on excision demonstrate a high rate of recurrence during a 1- to 6-year follow-up.4 Recurrences are typically managed with local reexcision. In conclusion, SAN is a benign, locally aggressive tumor of the breast that must be considered in any patient who presents with an areolar mass and suggestive findings on mammography. Identification of this benign process is critical to avoid misdiagnosis and subsequent unnecessary surgery and psychological stress.
Additional Contributions: Dorothea Barton, MD, Dartmouth-Hitchcock Medical Center, prepared the histopathologic photographs. No financial compensation was provided.
4. Page RN, Dittrich L, King R, Boulos F, Page DL. Syringomatous adenoma of the nipple occurring within a supernumerary breast: a case report. J Cutan Pathol. 2009;36(11):1206-1209.
REFERENCES
5. Bier-Laning CM, Hom DB, Gapany M, Manivel JC, Duvall AJ III. Microcystic adnexal carcinoma. Laryngoscope. 1995;105(11):1197-1201.
1. Oo KZ, Xiao PQ. Infiltrating syringomatous adenoma of the nipple. Arch Pathol Lab Med. 2009; 133(9):1487-1489. 2. Carter E, Dyess DL. Infiltrating syringomatous adenoma of the nipple: a case report and 20-year retrospective review. Breast J. 2004;10(5):443-447. 3. Coulthard A, Liston J, Young JR. Case report: infiltrating syringomatous adenoma of the breast—appearances on mammography and ultrasonography. Clin Radiol. 1993;47(1):62-64.
6. Carroll P, Goldstein GD, Brown CW Jr. Metastatic microcystic adnexal carcinoma in an immunocompromised patient. Dermatol Surg. 2000;26(6):531-534. 7. Ohta M, Hiramoto M, Ohtsuka H. Metastatic microcystic adnexal carcinoma: an autopsy case. Dermatol Surg. 2004;30(6):957-960.
JAMA Dermatology February 2015 Volume 151, Number 2 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Georgetown University Medical Center User on 05/22/2015
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