Definition/General

Introduction:
-Tubular carcinoma is a well-differentiated subtype of invasive ductal carcinoma of the breast
-It is characterized by the presence of well-formed tubules composed of a single layer of epithelial cells
-It accounts for approximately 1-2% of all invasive breast cancers and typically has an excellent prognosis.
Origin:
-Originates from the terminal duct-lobular unit (TDLU)
-The neoplastic cells form well-defined tubules that infiltrate the stroma
-The tubules are typically small, round to oval, and have open lumina
-The surrounding stroma is often desmoplastic.
Classification:
-Classified as a subtype of invasive ductal carcinoma
-To be classified as pure tubular carcinoma, at least 90% of the tumor must exhibit a tubular pattern
-It is almost always Grade 1 in the Nottingham grading system due to its high degree of differentiation.
Epidemiology:
-Typically affects older women, with a mean age of diagnosis in the early 60s
-It is rare in women under 40
-It is often detected on screening mammography as a small, spiculated mass
-The incidence has been stable over the past few decades.

Clinical Features

Presentation:
-Often presents as a small, palpable mass
-May be detected as a spiculated density on mammography
-Nipple discharge is rare
-Skin changes are uncommon due to the small size at diagnosis.
Symptoms:
-Usually asymptomatic and found on screening
-If palpable, it is typically a small, firm, non-tender mass
-Pain is uncommon
-Axillary lymphadenopathy is rare at presentation.
Risk Factors:
-Risk factors are similar to other types of breast cancer, including age, family history, and hormonal factors
-No specific risk factors unique to tubular carcinoma have been identified.
Screening:
-Mammography is the primary screening tool
-Tubular carcinomas often appear as small, irregular, spiculated masses with or without calcifications
-Ultrasound can also be used for evaluation.

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Gross Description

Appearance:
-Typically a small, firm, irregular mass
-The cut surface is gray-white and gritty
-The margins are often ill-defined and spiculated
-Necrosis and hemorrhage are rare.
Characteristics:
-The tumor is usually less than 2 cm in diameter
-The consistency is firm to hard
-The cut surface has a characteristic gritty or "crunchy" texture due to the desmoplastic stroma.
Size Location:
-Average size is around 1 cm
-Most commonly located in the upper outer quadrant of the breast
-Multifocality and multicentricity are uncommon.
Multifocality:
-Pure tubular carcinomas are usually unifocal
-When associated with other types of carcinoma, multifocality may be present
-Contralateral breast cancer is rare.

Microscopic Description

Histological Features:
-Characterized by well-formed, haphazardly arranged tubules infiltrating a desmoplastic stroma
-The tubules are composed of a single layer of uniform epithelial cells
-Myoepithelial cells are absent, which is a key feature of invasion.
Cellular Characteristics:
-The cells are small, uniform, and cuboidal with scant eosinophilic cytoplasm
-Nuclei are small, round, and regular with inconspicuous nucleoli
-Mitotic activity is low
-Apical snouts may be seen.
Architectural Patterns:
-The predominant pattern is well-formed tubules
-The tubules are often angulated or tear-drop shaped
-A cribriform pattern of DCIS is often associated with tubular carcinoma.
Grading Criteria:
-Almost always Grade 1 according to the Nottingham grading system
-Tubule formation is high (Score 1)
-Nuclear pleomorphism is low (Score 1)
-Mitotic count is low (Score 1).

Immunohistochemistry

Positive Markers:
-Strongly positive for Estrogen Receptor (ER) and Progesterone Receptor (PR)
-Negative for HER2
-E-cadherin is positive, confirming its ductal origin
-Cytokeratin 7 (CK7) is also positive.
Negative Markers:
-HER2 is negative
-Myoepithelial markers (p63, calponin, SMA) are negative around the invasive tubules, confirming invasion
-Basal cytokeratins (CK5/6, CK14) are negative.
Diagnostic Utility:
-IHC is crucial for confirming the diagnosis and ruling out mimics
-Absence of myoepithelial markers confirms invasion
-ER, PR, and HER2 status are essential for guiding therapy.
Molecular Subtypes:
-Almost exclusively of the Luminal A molecular subtype (ER+, PR+, HER2-, low Ki-67), which is associated with a good prognosis.

Molecular/Genetic

Genetic Mutations:
-Low frequency of TP53 mutations
-PIK3CA mutations are relatively common
-Loss of heterozygosity at 16q is a frequent finding
-Overall, it has a low genomic instability.
Molecular Markers:
-Low Ki-67 proliferation index
-Low expression of proliferation-associated genes
-High expression of luminal-related genes.
Prognostic Significance:
-Excellent prognosis with a 10-year survival rate of over 95%
-Lymph node metastasis is rare, occurring in about 10-15% of cases
-Distant metastasis is very uncommon.
Therapeutic Targets:
-Due to high ER/PR positivity, endocrine therapy (e.g., tamoxifen, aromatase inhibitors) is the mainstay of adjuvant treatment
-Chemotherapy is rarely indicated.

Differential Diagnosis

Similar Entities:
-Sclerosing adenosis (benign, retains myoepithelial layer)
-Microglandular adenosis (benign, lacks myoepithelial layer but is S100 positive)
-Radial scar/complex sclerosing lesion (benign, entrapped glands retain myoepithelial cells)
-Other well-differentiated invasive carcinomas.
Distinguishing Features:
-Sclerosing adenosis has a lobulocentric architecture and a myoepithelial layer
-Microglandular adenosis is S100 positive and ER/PR negative
-Radial scars have a central fibroelastotic core and entrapped glands with myoepithelial cells.
Diagnostic Challenges:
-Distinguishing from benign sclerosing lesions can be challenging on core biopsy
-The key is to demonstrate the absence of a myoepithelial layer around the tubules in the suspected invasive component.
Rare Variants:
-Pure tubular carcinoma is the main entity
-Mixed tubular carcinomas have a component of other types of invasive ductal carcinoma, which may affect prognosis.

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Specimen Information

[specimen type], measuring [size] cm in greatest dimension

Diagnosis

[diagnosis name]

Classification

Classification: [classification system] [grade/type]

Histological Features

Shows [architectural pattern] with [nuclear features] and [mitotic activity]

Size and Extent

Size: [X] cm, extent: [local/regional/metastatic]

Margins

Margins are [involved/uninvolved] with closest margin [X] mm

Lymphovascular Invasion

Lymphovascular invasion: [present/absent]

Lymph Node Status

Lymph nodes: [X] positive out of [X] examined

Special Studies

IHC: [marker]: [result]

Molecular: [test]: [result]

[other study]: [result]

Final Diagnosis

Final diagnosis: [complete diagnosis]