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'Histology and Immunophenotype of Invasive Lobular Breast Cancer Varga, Z; Mallon, E (2009). Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice and Pitfalls. Breast Disease, 30:15-19. Postprint available at: http://www.zora.uzh.ch University of Zurich Posted at the Zurich Open Repository and Archive, University of Zurich. Zurich Open Repository and Archive http://www.zora.uzh.ch Originally published at: Breast Disease 2009, 30:15-19. Winterthurerstr. 190 CH-8057 Zurich http://www.zora.uzh.ch Year: 2009 Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice and Pitfalls Varga, Z; Mallon, E Varga, Z; Mallon, E (2009). Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice and Pitfalls. Breast Disease, 30:15-19. Postprint available at: http://www.zora.uzh.ch Posted at the Zurich Open Repository and Archive, University of Zurich. http://www.zora.uzh.ch Originally published at: Breast Disease 2009, 30:15-19. Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice and Pitfalls Abstract Invasive lobular carcinomas (ILC) represent the most common subtype of invasive breast cancer and account for about 5-15% of all breast cancer cases. Invasive lobular carcinoma is often accompanied by in situ lesions, by lobular neoplasia (LN). Invasive lobular carcinomas display diverse histologic patterns varying from classical through solid to pleomorphic subtypes. When analyzing histological subtypes, the classical variant is reported to have a more favorable outcome. The majority of invasive lobular carcinomas are hormone receptor positive, overexpression and/or amplification of the Her2 gene is lower than in carcinomas of invasive ductal type. Loss of heterozygosity of the 16q chromosomal regions and the consequent lack of E-Cadherin expression are common findings in invasive lobular carcinomas. Intra-operative evaluation of resection margins in ILC is often unsatisfactory due to the diffuse nature of the tumor. Size estimation of the invasive component poses a similar challenge in daily practice. Galley Proof 24/07/2009; 14:06 File: BD278.tex; BOKCTP/sx p. 1 Breast Disease 30 (2009) 1–5 1 IOS Press Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily practice and pitfalls Zsuzsanna Varga∗ and Elizabeth Mallon aInstitute of Surgical Pathology, University Hospital Zurich, Switzerland bPathology Department Western Ifirmary Glasgow G11 6NT, UK Abstract. Invasive lobular carcinomas (ILC) represent the most common subtype of invasive breast cancer and account for about 5–15% of all breast cancer cases. Invasive lobular carcinoma is often accompanied by in situ lesions, by lobular neoplasia (LN). Invasive lobular carcinomas display diverse histologic patterns varying from classical through solid to pleomorphic subtypes. When analyzing histological subtypes, the classical variant is reported to have a more favorable outcome. The majority of invasive lobular carcinomas are hormone receptor positive, overexpression and/or amplification of the Her2 gene is lower than in carcinomas of invasive ductal type. Loss of heterozygosity of the 16q chromosomal regions and the consequent lack of E-Cadherin expression are common findings in invasive lobular carcinomas. Intra-operative evaluation of resection margins in ILC is often unsatisfactory due to the diffuse nature of the tumor. Size estimation of the invasive component poses a similar challenge in daily practice. GROSS PATHOLOGY sical infiltrative subtype [1–4]. Invasive lobular carci- nomas display characteristic cytologic features and a Invasive lobular carcinomas present mostly as an ir- distinct infiltration pattern of the stroma. Classical in- regular, infiltrating, poorly delineated mass rather than vasive lobular carcinomas are composed of single cells, a sharply demarcated lesion. Invasive lobular carcino- infiltrating in strands. In some cases focal tubule for- mas often display multifocality in the ipsilateral breast mation is seen. The classic pattern of invasive lobular and have a higher tendency to develop bilaterality than carcinomas are characterized by a small uniform cell other tumor types. The size of the invasive component population, lacking cohesion and invading the stroma varies considerably (from millimeters to several cen- as individual tumor cells, resulting in a ‘single-file’ or timeters). The edges of the tumor mass are often diffi- cult to evaluate and may be best appreciated by palpa- ‘Indian-file’ pattern of growth. Sometimes tumor cells tion. The cut surface often appears as an inconspicu- are located around benign ducts in a circular fashion ous, grey or white area. In other cases there is no gross- resulting in a targetoid appearance. Tumor cells usu- ly visible mass and the tumor can only be appreciated ally have a round nucleus, thin cytoplasm with occa- by palpation or not at all [1–4]. sional cytoplasmic vacuoles. The nuclei are usually small, eccentric and show little variation in size, nu- cleoli are absent or inconspicuous. Mitotic figures are GENERAL HISTOLOGICAL ASPECTS rare. The classical form of invasive lobular carcino- ma is often accompanied by in situ lesions of lobular The original definition of invasive lobular carcinoma neoplasia occurring in 40–60% of invasive carcinomas. comes from Stewart and Foote, who described the clas- Invasive lobular carcinoma is sometimes accompanied by a prominent lymphocytic or granulomatous reac- ∗Corresponding author. E-mail: [email protected]. tion. The histological diagnosis of classical lobular 0888-6008/09/$17.00 © 2009 – IOS Press and the authors. All rights reserved Galley Proof 24/07/2009; 14:06 File: BD278.tex; BOKCTP/sx p. 2 2 Z. Varga and E. Mallon / Histology and Immunophenotype of Invasive Lobular Breast Cancer Fig. 1. Special types of invasive lobular breast cancer. A) classical type (HE). B) histiocytoid variant (HE). C) pleomorphic variant (HE). D) alveolar variant (HE). Magnification: 300X. carcinomas requires at least 70% of single-file growth and invasive classical lobular carcinoma, traditionally pattern [1–4]. categorized as a variant of invasive lobular carcinoma. Pleomorphic variant: this variant represents a dis- tinct subtype of invasive lobular carcinoma with similar SPECIAL SUBTYPES OF INVASIVE LOBULAR growth pattern and stroma infiltration as seen in oth- CARCINOMA (see Figs 1 and 2) er subtypes. However, the tumor cells are larger and exhibit more cellular atypia and pleomorphism. The cytoplasm is more abundant and it often shows some Several histological variants of invasive lobular car- eosinophilia. Recurrence free survival is reportedly cinoma have been described. poorer in pleomoprhic lobular carcinomas than in clas- Solid pattern: this pattern is characterized by sheets sical lobular carcinomas. Pleomorphic lobular carci- of uniform cells, lacking cohesion, resulting in a growth nomas can display apocrine, signet ring cell and histi- pattern in large confluent areas with little or absent cytoid differentiation. Apocrine differentiation in in- stroma in between. vasive lobular carcinomas has been found to have an Alveolar pattern: in this variation tumor cells are especially aggressive clinical course. arranged in small clusters or nests of approximately 20 Histiocytoid variant: in this variant tumor cells have cells, separated by delicate fibrovascular septa. a pale appearance with foamy cytoplasm and mild nu- Trabecular pattern: this variant represents a histo- clear variation. logical overlap between classical and so called trabec- Signet cell variant: this subtype occurs in invasive ular filing pattern. This morphological coincidence is breast carcinomas with a growth pattern of a lobular due to the morphological similarity between ‘single carcinoma, consisting of a prominent component of file’ seen in the classical variant and ‘one-cell-thick- signet ring cells. trabecules’ observed in the trabecular variant. Mixed lobular carcinomas: this group shows an ad- Tubulolobular pattern: this lesion is composed of mixture of classical lobular carcinoma accompanied by small tubular structures as well of single cell files seen at least one more additional pattern, which could be in classical lobular carcinomas. This category repre- either a special type of invasive lobular carcinoma or sents a morphological overlap between invasive tubular of invasive ductal carcinoma [1–4]. Galley Proof 24/07/2009; 14:06 File: BD278.tex; BOKCTP/sx p. 3 Z. Varga and E. Mallon / Histology and Immunophenotype of Invasive Lobular Breast Cancer 3 Fig. 2. Special types of invasive lobular breast cancer. A) intracellular mucin production (HE). B) intracellular mucin production (Alcian blue PAS). C) Mixed carcinoma, ductal (left) and lobular (right) (HE). D) Negative immunoreactivity for E-Cadherin (E-Cadherin). Magnification: 300X (A,B,D) 50X (C). GRADING OF INVASIVE LOBULAR lenge preferentially occurs with suboptimal tissue fix- CARCINOMA ation. The use of immunohistochemistry (cytokeratin in the neoplastic cells) or the detection of cytoplas- Grading of invasive lobular carcinomas is widely mic vacuoles containing mucin, should easily identi- accepted in routine surgical pathology despite the fact, fy the lesion as invasive lobular carcinoma. Rarely, that the application of BRE Score is somewhat special inflammatory cells can mimic invasive lobular cancer in this tumor type. There is no tubular formation in cells, which can be challenging particularly on frozen invasive lobular carcinomas, therefore, a score of 3 has sections. The evidence of in situ components, lobular to be attributed
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