Breast malignant, males, children - Classic infiltrating lobular carcinoma

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Breast malignant, males, children

Carcinoma subtypes

Classic infiltrating lobular carcinoma

Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 29 October 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

See variants: alveolar, basal-like, histiocytoid, pleomorphic, signet-ring, solid, trabecular

General
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● Invasive tumor associated with LCIS, composed of noncohesive cells that are individually dispersed or arranged in a single file pattern (Stanford University)
● Minimal desmoplastic response

Clinical features
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● 10% of all breast carcinomas
● Incidence decreasing in US (Cancer Epidemiol Biomarkers Prev 2009;18:1763)
● 10-20% are bilateral; multicentricity within same breast is more common than invasive ductal carcinoma
● Often not well seen on mammograms, and may be more extensive than clinically suspected
● Metastasizes to bone marrow, cerebrospinal fluid and leptomeninges (Arch Pathol Lab Med 1991;115:507), GI tract, ovary, serosal surfaces, uterus (resembles low grade stromal sarcoma) more than other subtypes
● Pan-keratin staining of negative bone marrow biopsies is recommended to detect metastases (Am J Surg Pathol 2000;24:1593, Hum Pathol 1994;25:781), but has minimal value for nodal metastases (Hum Pathol 2008;39:1011)
● Lack of cohesion due to alterations in E-cadherin, an adhesion molecule that is deleted or mutated
● Variants usually coexist with classic pattern

Case reports
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● 58 year old man with carcinomatosis (Am J Surg Pathol 2009;33:470)
● 60 year old woman whose tumor had pools of extracellular mucin (Pathol Int 2009;59:405)
● 61 year old woman with c-kit+ gastric metastasis resembling GIST tumor (Breast Cancer 2010;17:303)
● 70 year old woman presenting with orbital mass (Intern Med 2012;51:1635)
● 88 year old woman with anal metastasis (World J Gastroenterol 2009;15:1388)
● With coexisting DCIS and LCIS, examined by comparative genomic hybridization (Hum Pathol 2004;35:759)
● Metastases to tamoxifen associated endometrial polyps (Mod Pathol 2003;16:395)
● Metastasis to uterus associated with anastrozole (anti-estrogen) therapy (Onkologie 2009;32:424)

Treatment
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● Classic variant has better prognosis than non-classic variants overall (Cancer 2008;113:1511, Am J Surg Pathol 1990;14:12)
● May have similar long term prognosis as infiltrating ductal carcinoma (Breast Cancer Res Treat 2009;117:211), but see J Clin Oncol 2008;26:3006 (lobular has better survival at 6 years but worse survival at 10 years)
● In one study, 12 year local relapse free survival was 89%; predictors of relapse were positive margins, age >50 years and contralateral breast cancer (Eur J Surg Oncol 2010;36:176)

Gross description
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● Mass with ill-defined margins; often no mass because of diffuse growth pattern

Gross images
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Solid firm mass

Infiltration into adipose tissue

Anal metastasis

Other images: Multiple foci with irregular margins #1, #2

Micro description
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● Cells grow in single file (linear, Indian file) or targetoid pattern of noncohesive cells encircling ducts, loosely dispersed throughout fibrous matrix
● Tumor cells are usually small, uniform, round with minimal pleomorphism, evenly disbursed chromatin and no nucleoli (i.e. nuclear grade 1, like LCIS cells)
● Commonly signet ring cells, intracellular lumina, intracellular mucin, LCIS (90%)
● Variable dense fibrous stroma with periductal and perivenous elastosis
● May have dense lymphoid infiltrate
● No glandular formation in classic cases, but may have preservation of normal glandular structures and “skip areas” uninvolved by tumor
● < 10 mitoses/10 HPF, no necrosis
● Histologic grading is recommended (Mod Pathol 2005;18:621)
● Most tumors are histologic grade 2 (Breast Cancer Res Treat 2008;111:121)
● 2 tiered nuclear grading system may reduce interobserver variability (Ann Diagn Pathol 2009;13:223), as may nuclear and proliferation grading system (Ann Clin Lab Sci 2009;39:25)

Bone marrow biopsies:
● Highly suspicious features for metastatic disease are fibrosis, signet ring cells, cells with intracytoplasmic lumina, cells resembling histiocytes
● Architecture is often NOT disrupted

Micro images
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Single file pattern


Classic features


Single dyscohesive cells

Minute focus (arrow) of tumor around a small duct (AFIP)

Classic targetoid (bulls eye) pattern of tumor cells around duct (AFIP)

With LCIS

Minimal tumor in core biopsy (Fig 1A/1B)


Grade I of III-minimal nuclear pleomorphism


Grade II of III-moderate nuclear pleomorphism

Grade III of III-severe nuclear pleomorphism

Tumor of male breast

Invasive lobular carcinoma within fibroadenoma:

Left to right: H&E (2), ER, CK5/6, E-cadherin

Metastases:

Endometrial polyp: H&E and AE1/AE3

Lymph node

Soft tissue


Stomach

Other images: single file pattern, prominent intracytoplasmic mucin, targetoid pattern #1, #2, with LCIS #1, #2

Virtual slides
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Lobular carcinoma

With LCIS

Cytology description
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● Moderate / highly cellular, pattern is predominantly or partly dissociated
● Usually small / intermediate cells with intracytoplasmic lumina in 57%, light cytoplasm
● Small, eccentric nuclei with finely granular chromatin (Acta Cytol 2000;44:169, Med Mol Morphol 2008;41:121, Cancer 2008;114:111)

Cytology images
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FNA shows small cells arranged in linear pattern (figure B)

Various images

Positive stains
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● ER, PR
● HMW keratin (helpful in bone marrow biopsy)
● Mucicarmine (intracellular mucin)
● GCDFP-15 (30%)
● PLEKHA7 (Hum Pathol 2012 Apr 25 [Epub ahead of print])

Negative stains
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● E-cadherin (complete absence suggests lobular carcinoma, but rarely is positive and may vary by antibody, Am J Surg Pathol 2008;32:773, Mod Pathol 2008;21:1224)
● p53, HER2, Ki-67

Molecular description
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● Usually diploid
● Truncation mutations in E-cadherin gene (16q) or inactivation of wild-type allele

Electron microscopic images
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Line of tumor cells surrounded by collagen, with cytokeratin bundles (arrows), but no basement membrane

Intracytoplasmic lumina lined by microvilli, elastic tissue (arrows) and collagen in stroma

Intracytoplasmic lumen with numerous microvilli and perinuclear mucin granules

Videos
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Differential diagnosis
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● Lymphoma: resembles lobular metastases to axillary nodes or eyelid
● Invasive ductal adenocarcinoma: may have focal lobular features, immunostains may be helpful (Appl Immunohistochem Mol Morphol 2012 May 16 [Epub ahead of print])
● Invasive ductal carcinoma with neuroendocrine features

End of Breast malignant, males, children > Carcinoma subtypes > Classic infiltrating lobular carcinoma

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