Tubular carcinoma of the breast is a distinct, relatively rare low-grade neoplasm, accounting for approximately 1 to 2% of invasive breast cancers. It is composed of well-differentiated tubular structures with open lumina, typically one layer thick surrounded by abundant stroma. Because of its nonaggressive, histologic appearance, its low propensity to recur locally, spread to axillary lymph nodes, and metastasize distantly, pure tubular carcinoma carries a favorable prognosis. Its diagnosis is established based on histopathological examination of the surgical specimen.
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.
Other alterations include loss of 8p, 3p (FHIT gene locus) and 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.
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.
Pure tubular carcinoma accounts for approximately 1 to 2% of invasive breast cancers. Its frequency is higher in populations where there is screening mammography.
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 cancers, 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.
Reports show a higher frequency in whites compared with blacks..
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 and 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 occurs in association with flat epithelial atypia, low-grade ductal carcinoma in situ, and less commonly tubular neoplasia . There is a lack of consensus concerning the proportion of tubular structures necessary for a diagnosis of tubular carcinoma, with the requirement set at between 75% and 100%, but 90% purity offers a practical solution and is recommended . Tumors exhibiting between 50% and 90% tubules admixed with another morphology should be regarded as being of mixed type.
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.
There is no specific clinical feature that 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.
The mammographic abnormality reported in the majority of patients with tubular carcinomas is a mass lesion with central density, occasionally with microcalcifications. 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 is particularly helpful in detecting some of the mammographically occult tumors. On ultrasonography, tubular carcinoma appears as an irregularly contoured mass with posterior acoustic shadowing.
Magnetic resonance imaging:
On magnetic resonance imaging, some authors observed enhancement patterns that could help to differentiate tubular carcinoma from other histological subtypes.
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, while others have questioned the prognostic value of axillary staging and the necessity of adjuvant systemic therapy. Until there is the 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. Due to the low invasiveness of tubular carcinoma, breast preservation therapy, with or without radiotherapy, is probably the best approach, in particular when no nodal metastasis presents. 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.
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 and 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. 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 (ER) 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 one or more nodes, one should consider giving adjuvant chemotherapy along with endocrine therapy.
Staging of tubular carcinoma of the breast is determined clinically by physical examination and imaging studies before treatment and is determined pathologically by pathologic examination of the primary tumor and regional lymph nodes after definitive surgical treatment. The most widely used clinical staging system for medullary breast carcinoma is the one adopted by both the International Union 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 five stages (stage 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.
Patients with pure tubular carcinoma have an excellent prognosis compared 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. Axillary lymph node metastases occur infrequently and rarely involve more than one axillary lymph node. Even when patients have axillary metastases from tubular carcinoma, the prognosis is very good.
Patients must be instructed to self-examine their breasts regularly and consult their doctors if any abnormality detected.
Tubular carcinoma is a special type of invasive carcinoma with a distinctive morphologic appearance and excellent prognosis. Management of tubular breast carcinoma needs a multidisciplinary approach involving a team that consists of a surgical oncologist, an oncologist, a pathologist, and a radiologist. Careful planning and discussion with other professionals involved in the management of patients with tubular carcinoma will improve patient outcomes. Despite its excellent prognosis, careful long-term follow-up is essential for tubular carcinoma because local recurrences can occur after many years. Moreover, the mammographic monitoring of the contralateral breast is critical. The primary care provider and nurse practitioner must refer patients with suspected breast masses to an oncologist for further work up.
Tubular carcinoma requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level V]
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