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Breast

Other invasive carcinoma subtypes, WHO classified

Tubular

Authors: Pragya Virendrakumar Jain, M.D., Julie M. Jorns, M.D.

Editorial Board Member: Kristen E. Muller, D.O.

Deputy Editor-in-Chief: Gary Tozbikian, M.D.

Last author update: 23 March 2023

Last staff update: 23 December 2024

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Tubular carcinoma breast

Table of Contents

Cite this page: Jain PV, Jorns JM. Tubular. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignanttubular.html. Accessed December 26th, 2024.

Definition / general

Special subtype of invasive breast carcinoma with favorable prognosis
Composed of distinct, well differentiated angular tubular structures (> 90%) with open lumina, lined by a single layer of low grade malignant epithelial cells, with a fibrous / desmoplastic stromal response

Essential features

> 90% of the tumor is composed of ovoid or angular tubules with open lumina lined by a single layer of epithelial cells with low grade nuclei and sparse mitoses (grade 1)
ER positive and HER2 negative

Terminology

Tubular carcinoma
Invasive tubular carcinoma

ICD coding

ICD-O: 8523/3 - infiltrating duct mixed with other types of carcinoma
ICD-10:
- C50.812 - malignant neoplasm of overlapping sites of left female breast
- C50.912 - malignant neoplasm of unspecified site of left female breast
ICD-11: 2C60 - carcinoma of breast, specialized type

Epidemiology

1.6% of invasive breast carcinomas
Postmenopausal women, median age at presentation is 63 years
Slightly higher incidence in white women than black women in the U.S.

Sites

Breast, with no specific site of predilection

Pathophysiology

Luminal A molecular subtype of breast cancer
Hypothesis: may arise due to a sequence of events starting with flat epithelial atypia
- Co-occurrence of columnar cell lesions, atypical ductal hyperplasia / ductal carcinoma in situ and pure form of tubular carcinoma with the same cytologic nuclear morphology has been observed (J Urol 1992;147:322)
- Rosen triad: tubular carcinoma, lobular carcinoma in situ, columnar cell lesions (Adv Anat Pathol 2008;15:140)

Etiology

No specific etiology: see etiologies associated with low grade, ER positive invasive breast cancer of no special type (NST)

Clinical features

Can be multifocal / multicentric (20 - 55%) (Am J Surg Pathol 1997;21:653)
May have family history of breast carcinoma (40%)
Usually presents as early stage, pT1 and pN0 disease (Int J Radiat Oncol Biol Phys 2009;75:1304)

Diagnosis

Histologic examination of tissue

Radiology description

Mammography: may present as a discrete or ill defined mass with well demarcated or spiculated, irregular margins, respectively or as an architectural distortion, with variable calcifications (Radiol Med 2006;111:773)
Ultrasonography: hypoechoic mass with poorly defined margins and posterior acoustic shadowing (Tumori 2003;89:417)
MRI: enhancing mass, enhancing focus or non mass enhancement (Egyptian J Radiol Nuc Med 2018;49:281)

Radiology images

Contributed by Julie M. Jorns, M.D.

Diagnostic mammogram

Prognostic factors

Well differentiated variant with very favorable prognosis (low rates of recurrence and metastasis) (Am J Surg 2009;197:674)
Longer disease free and breast cancer specific survival with tubular carcinoma (n = 102) as compared to grade 1 invasive ductal carcinoma of no special type (n = 212) (J Clin Oncol 2010;28:99)
Higher disease free survival was seen with pure tubular histology as well as if 3 criteria were met (≥ 70% tubules, pure grade 1 nuclei and no / rare mitoses) in a cohort of grade 1 - 2 tubular (n = 32) and invasive ductal (n = 115) carcinomas (Am J Clin Pathol 2004;122:728)
Mixed with invasive ductal carcinoma of no special type has a worse prognosis (Hum Pathol 1983;14:694)
Cause specific survival of 97% at 10 years (Eur J Surg Oncol 2005;31:9)
10 - 27% have axillary metastases, often micrometastases but still have excellent prognosis (Eur J Surg Oncol 2006;32:488, Breast J 2003;9:298)

Case reports

39 and 74 year old women who presented with tubular carcinoma in retroareolar and deep parasternal locations, respectively (Medicine (Baltimore) 2021;100:e24977)
46 year old woman with tubular carcinoma presenting as non mass enhancement (Egyptian J Radiol Nuc Med 2018;49:281)
63 year old woman with tubular carcinoma that spontaneously shrank from 9 mm to 4 mm on breast imaging during the 6 year interval from first identification to diagnostic biopsy (Radiol Case Rep 2015;1:68)

Treatment

Surgery, either breast conserving surgery (lumpectomy) or mastectomy, with or without radiation therapy depending on surgery and clinical features (Breast Cancer Res Treat 2005;93:199, Breast J 2005;11:129)
Axillary lymph node staging, including sentinel lymph node excision, may be safely omitted (Eur J Surg Oncol 2013;39:248, Ann Surg Oncol 2023;30:1042)
May be offered anti-endocrine therapies
Adjuvant chemotherapy is contraindicated

Gross description

Spiculated tumor with a firm consistency; may have gritty texture if there are calcifications
Mean size is 1.2 cm
White, tan or gray in color

Gross images

Images hosted on other servers:

Yellow-white sclerotic mass

Microscopic (histologic) description

Invasive breast cancer with infiltrative growth pattern, often with invasion into adipose tissue and with an associated fibrous or desmoplastic stromal response
- No myoepithelium surrounding the tubules
> 90% of the tumor is composed of small, ovoid or angulated tubules with open lumina
Tubules are lined by a single layer of epithelial cells with low grade nuclei and sparse mitoses (grade 1)
- Tumor cells often have apical cytoplasmic tufting or snouts
- Cells lining the neoplastic tubules are cuboidal to columnar with uniform, small to intermediate sized nuclei
- No significant cytologic atypia, multilayering or high mitotic activity (the presence of these would rule out tubular carcinoma)
- There may be luminal secretions or calcifications
Tumor cells are ER positive and HER2 negative
Recent study shows that the actual structure is not tubular, instead it simulates a beaded necklace
- 2 dimensional microscopy and 3 dimensional modeling studies revealed that structure resembled a necklace formed by a string of beads with the tubules visualized as blebs bridged together by solid cords of cells; continuous or branching tubules were not seen (Histopathology 2006;48:556)
Desmoplastic or fibroelastotic stroma
Frequent presence of associated nonobligate precursors:
- Columnar cell lesions (95%), in particular flat epithelial atypia (Am J Surg Pathol 2007;31:417, Pathol Int 2008;58:620)
- Atypical ductal hyperplasia
- ER positive low grade DCIS
- Rosen triad: tubular carcinoma, lobular carcinoma in situ, columnar cell lesions (Adv Anat Pathol 2008;15:140)

Microscopic (histologic) images

Contributed by Julie M. Jorns, M.D., Mark R. Wick, M.D. and AFIP

Infiltrative angulated tubules

Angulated tubules

Apical tufting

Desmoplasia

Associated ADH, FEA and ALH

Associated atypical lobular hyperplasia

Associated atypical ductal hyperplasia / flat epithelial atypia

Apical tufting

Open tubules

Angular glands with cytoplasmic snouts

Virtual slides

Images hosted on other servers:

Invasive tubular carcinoma

Cytology description

Increased cellularity, somewhat angular or irregular or small tubular epithelial clusters and single epithelial cells
Cells are bland and orderly with variable atypia and a variable number of prominent myoepithelial cells
Features of malignancy such as nuclear atypia, absence of myoepithelial cells and cellular dissociation are subtle and hence diagnosis on cytology can be challenging (Acta Cytol 1997;41:1139, Am J Clin Pathol 1994;101:488)

Positive stains

ER, PR and E-cadherin
CK8, CK 8/18 (luminal phenotype)

Negative stains

HER2 (ERBB2), HER1 (EGFR), p53 (Am J Clin Pathol 2006;126:55)
Myoepithelial markers (p63, CD10, smooth muscle actin, CK5/6)
P-cadherin
CK5 / CK14 (luminal phenotype)

Electron microscopy description

Ductal differentiation, no myoepithelial cells and no basement membrane

Molecular / cytogenetics description

ER positive pathway alterations
- Frequent alterations: loss of 16q (78 - 86%), gains of 1q (50 - 62%), both usually occur concurrently
- Infrequent alterations: 16p gain, loss of 8p, 3p (the FHIT gene locus) and 11q (the ATM gene locus)
Fewer overall chromosomal changes than invasive ductal carcinoma of no special type (Hum Pathol 2001;32:222)
Clonally related to flat epithelial atypia and low grade DCIS (Am J Surg Pathol 2009;33:1646)

Sample pathology report

Right breast, ultrasound guided core biopsy:
- Invasive mammary carcinoma with tubular features, preliminary modified Bloom-Richardson grade 1 (1+2+1) (see comment)
- Estrogen receptor: (91 - 100%, strong) positive
- Progesterone receptor: (91 - 100%, strong) positive
- HER2 / neu: (1+) negative for overexpression
- Comment: The carcinoma in this biopsy has entirely tubular features. If there is similar morphology in > 90% of the tumor on resection it would be best classified as an invasive tubular carcinoma.

Differential diagnosis

Sclerosing adenosis:
- Overall lobular architecture but with distortion by fibrosis, compression of glands with 2 layers (inner epithelial and outer myoepithelial)
- Positive for myoepithelial markers (Appl Immunohistochem Mol Morphol 2006;14:71)
Radial scar:
- Desmoplastic / elastotic stroma, bland tubules
- Does not infiltrate at the periphery
- Often has intermixed fibrocystic changes such as cysts and usual ductal hyperplasia
- Retained myoepithelial cell layer
Microglandular adenosis:
- More rounded (not angulated) tubules with intraluminal colloid-like secretory material (Am J Surg Pathol 1982;6:401)
- Lacks myoepithelium but basement membrane material is present
- ER negative and S100 positive
Mixed tumors with a combination of tubular carcinoma and another subtype of cancer:
- Should be reported when the tumor mass shows 10 - 90% tubular carcinoma (common) or ≥ 90% is tubular carcinoma and remaining tumor shows nuclear grade 3 (rare)
Tubulolobular carcinoma:
- Mixed tubular and lobular components
- Not an entity in WHO
- Thought to be a variant of tubular carcinoma as they share similar architectural and growth patterns (tubulolobular carcinoma also resembles a beaded necklace but with longer connecting strands of single cells)
- Both show E-cadherin positivity
- Both show indolent clinical behavior
Low grade adenosquamous carcinoma:
- Squamous differentiation
- Less uniformity (open and compressed tubules, nests)
- Often ER negative
Low grade invasive ductal carcinoma of no special type:
- Similar low grade cytologic features to tubular carcinoma, with or without prominent apical cytoplasmic tufting but with more complex architecture
- Tumor shows multilayering, stratification, glandular fusion or branching and may have > 10% ribbons or cords
- ER expression is often high but may be of lower intensity in tubular carcinoma (i.e., third quartile or > 50 - 75%, expression) than in well differentiated invasive ductal carcinoma (i.e., fourth quartile or > 75 - 100%, expression) (Arch Pathol Lab Med 2014;138:1507)

Additional references

WHO Classification of Tumours Editorial Board: Breast Tumours, 5th Edition, 2019

Board review style question #1

A postmenopausal woman presented with a breast mass measuring 0.8 cm. Biopsy and resection showed the morphology seen in the image above in > 90% of the tumor. What is the expected immunoprofile?

ER / PR positive, HER2 negative
ER / PR positive, HER2 positive
ER / PR negative, HER2 positive
ER / PR negative, HER2 negative

Board review style answer #1

A. ER / PR positive, HER2 negative. The tumor consists of infiltrative small, angulated tubules with a single layer of low grade neoplastic epithelium with prominent apical tufting, features diagnostic of tubular carcinoma. Tubular carcinoma is a luminal A breast carcinoma and thus is ER / PR positive and HER2 negative.

Comment Here

Reference: Tubular carcinoma of breast

Board review style question #2

A core biopsy of a breast mass shows an invasive carcinoma with tubular features. What are the essential criteria to diagnose this tumor as tubular carcinoma?

> 90% tubules lined by highly pleomorphic epithelial cells and brisk mitosis
> 90% tubules lined by low grade epithelial cells with sparse mitosis
< 90% tubules lined by highly pleomorphic epithelial cells and brisk mitosis
< 90% tubules lined by low grade epithelial cells with sparse mitosis

Board review style answer #2

B. > 90% tubules lined by low grade epithelial cells with sparse mitosis. The diagnosis of tubular carcinoma or any special subtype of invasive breast carcinoma, requires that > 90% of the tumor show the specific diagnostic features of the special subtype. Thus, in the case of tubular carcinoma, > 90% of the tumor must have small, angulated tubules lined by a single layer of low grade malignant epithelium and sparse to absent mitoses. Because the patient underwent core biopsy, which is only a sampling of the tumor, the designation as tubular carcinoma should be reserved until the tumor is fully evaluated on subsequent resection. In such cases, a note or comment can be helpful (please see Sample pathology report for an example).

Comment Here

Reference: Tubular carcinoma of breast

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