Tubular Breast Carcinoma

Etiology

Genetic alterations in tubular carcinoma are uncommon. They mainly include chromosomes 16q (loss) (78 to 86%) and 1q (gain) (50 to 62%), and they often occur concomitantly.[3] Other alterations include loss of 8p, 3p (FHIT gene locus), 16p gain, and 11q (ATM gene locus). Gene expression profiling studies have proven that tubular carcinoma belongs to the “luminal A” molecular class of breast cancer.[3] Studies analyzing morphologic features of tumors arising in carriers of BRCA1 or BRCA2 mutations and non-BRCA1/2 families have not reported a frequent association of tubular carcinoma in these subsets of patients. 

Epidemiology

Pure tubular carcinoma accounts for approximately 1 to 2% of invasive breast cancers. Its frequency is higher in populations where there is screening mammography.[4] Tubular carcinomas predominate in women in their sixth or seventh decade who underwent breast cancer screening (mean age at onset is between 54 and 60 years). As for other forms of breast cancer, tubular carcinoma is very rare in male patients. Its preferential site of involvement is in the upper outer quadrant of the breast. Multifocality presents in 20% of the cases.[4] Reports show a higher frequency in whites compared with blacks.[5].

Histopathology

Macroscopy

Tubular carcinoma often presents like an ill-defined grey to a white, firm, or hard mass measuring between 0.2 cm and 2 cm in diameter; most are 1.5 cm or less.[6][7]

Histopathology 

The characteristic feature of tubular carcinoma is the predominance of open tubules composed of a single layer of epithelial cells enclosing a clear lumen. These should comprise over 90% of the tumor. The tubules are generally an admixture of oval or rounded, angulated shapes and arranged haphazardly. The cells are small to moderate in size, regular with little nuclear pleomorphism, inconspicuous nucleoli, and scanty mitotic figures. Myoepithelial cells are absent around the tubules, but some may have an incomplete surrounding layer of the basement membrane. A secondary but essential feature is the cellular desmoplastic stroma, commonly accompanying the tubular structures. Tubular carcinoma is associated with flat epithelial atypia, low-grade ductal carcinoma in situ, and, less commonly, tubular neoplasia [8][2]. There is a lack of consensus concerning the proportion of tubular structures necessary for diagnosing tubular carcinoma, with the requirement between 75% and 100%. However, 90% purity offers a practical solution and is recommended [2]. Tumors exhibiting between 50% and 90% tubules admixed with another morphology should be regarded as mixed type.

Immunohistochemistry

Tubular carcinoma is nearly always positive for estrogen and progesterone receptors, has a low growth fraction, and is typically negative for HER2, EGFR, P-cadherin, p53, and high molecular weight keratins.[9][3]

History and Physical

No specific clinical feature distinguishes tubular carcinoma from the more common invasive carcinomas of no particular type or other types. Initially, tubular breast carcinoma may not cause any symptoms. Over time, a lump may grow large enough to be detected during breast self-examination or examination by a doctor. Tubular carcinomas are usually small, measuring 1 cm or less in diameter, and are firm or hard in consistency.

Evaluation

Mammography

The mammographic abnormality reported in most patients with tubular carcinomas is a mass lesion with central density, occasionally with microcalcifications.[10][11][12] The mass may appear round, oval, or lobulated, with irregular or spiculated margins. Tubular carcinomas cannot be distinguished reliably from invasive duct carcinomas and sometimes from radial scars on imaging studies, as these lesions show similar architectural patterns. Because of the high incidence of other types of coexisting carcinoma in the ipsilateral or developing carcinoma in the contralateral breast, bilateral mammography at the time of diagnosis is important.

Ultrasonography

Ultrasonography is particularly helpful in detecting some of the mammographically occult tumors.[13] On ultrasonography, tubular carcinoma appears as an irregularly contoured mass with posterior acoustic shadowing.[11]

Magnetic Resonance Imaging

On magnetic resonance imaging, some authors observed enhancement patterns that could help to differentiate tubular carcinoma from other histological subtypes.[14]

Treatment / Management

Because of its favorable prognosis, some studies have proposed that a diagnosis of tubular carcinoma might warrant less aggressive surgical or adjuvant treatment. Specifically, some have challenged the need for radiation therapy for patients who have undergone breast-conserving surgery [15], while others have questioned the prognostic value of axillary staging and the necessity of adjuvant systemic therapy.[16][6] Until there is a better establishment of the value of nodal status, lymph node evaluation should still be considered in patients with tumors of less than 1 cm because a small primary tumor size does not preclude nodal involvement.[12] Due to the low invasiveness of tubular carcinoma, breast preservation therapy, with or without radiotherapy, is probably the best approach,[4] in particular when no nodal metastasis presents.[17] According to some authors, adjuvant radiation therapy reduces the incidence of local failure following conservative surgery for tubular carcinoma. However, elderly tubular patients treated by conservative surgery appear to have a very low risk of local recurrence without radiation therapy.(B2)

Because almost all tubular carcinomas express hormone receptors, some form of adjuvant hormonal treatment applies to most patients. The decision regarding systemic adjuvant chemotherapy should be individualized based on tumor size, grade, and lymph node status. Chemotherapy is typically not recommended to patients with tubular carcinoma given the excellent prognosis, low risk for recurrence, and adverse side effects that significantly outweigh the small benefit chemotherapy may have.[18] The 2015 National Comprehensive Cancer Network guidelines do not recommend adjuvant endocrine therapy for patients with tumors less than 10 mm and favorable histology, such as tubular carcinoma with or without micrometastasis or isolated tumor cells in lymph nodes. If the tumor is estrogen receptor positive, one may consider endocrine therapy for risk reduction and to diminish the small risk of disease recurrence. If the tumor is between 10 and 29 mm, one should consider giving adjuvant endocrine therapy. In patients with tumors more than or equal to 30 mm, adjuvant endocrine therapy should be the treatment. In patients with macrometastasis in 1 or more nodes, one should consider giving adjuvant chemotherapy along with endocrine therapy.

Differential Diagnosis

The differential diagnosis for tubular breast carcinoma includes the following: 

• Sclerosing adenosis
• Complex sclerosing lesions / radial scars
• Microglandular adenosis
• Low-grade invasive carcinoma of no special type
• Tubulo-lobular carcinomas

Staging

Staging of tubular carcinoma of the breast is determined clinically by physical examination and imaging studies before treatment. It is determined pathologically by pathologic examination of the primary tumor and regional lymph nodes after definitive surgical treatment. The International Union adopts the most widely used clinical staging system for medullary breast carcinoma for Cancer Control (UICC) and the American Joint Commission on Cancer (AJCC). Its basis is in the TNM system (T, tumor; N, nodes; M, metastases). T, N, and M are combined to create 5 stages (stages 0, I, II, III, and IV) that summarize information about the extent of the regional disease (tumor size, skin, or chest-wall invasion and nodal involvement) and metastasis to distant sites.

Prognosis

Patients with pure tubular carcinoma have an excellent prognosis compared with patients with invasive ductal carcinoma. Ten-year disease-free survival and overall survival rates after mastectomy or partial resection have been reported to be 93.1 to 99.1% and 99 to 100%, respectively.[19][3] Axillary lymph node metastases occur infrequently and rarely involve multiple axillary lymph nodes. Even when patients have axillary metastases from tubular carcinoma, the prognosis is very good.

Complications

Lymph Node Metastases

Lymph node metastases in patients with tubular carcinoma vary between 0 and 20%.[12]

Recurrence

The recurrence rate (local or systemic) of tubular carcinoma reported in the literature is 8% or less after mastectomy.[11]