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. 2024 Aug 1;25(15):8382.
doi: 10.3390/ijms25158382.

The "Forgotten" Subtypes of Breast Carcinoma: A Systematic Review of Selected Histological Variants Not Included or Not Recognized as Distinct Entities in the Current World Health Organization Classification of Breast Tumors

Nektarios I Koufopoulos  1 , Ioannis Boutas  2 , Abraham Pouliakis  1 , Menelaos G Samaras  1 , Christakis Kotanidis  1 , Adamantia Kontogeorgi  3 , Dionysios T Dimas  4 , Argyro-Ioanna Ieronimaki  1 , Danai Leventakou  1 , Aris Spathis  1 , Magda Zanelli  5 , Andrea Palicelli  5 , Maurizio Zizzo  6   7 , Dimitrios Goutas  8 , Ioannis S Pateras  1 , Ioannis G Panayiotides  1
Affiliations

The "Forgotten" Subtypes of Breast Carcinoma: A Systematic Review of Selected Histological Variants Not Included or Not Recognized as Distinct Entities in the Current World Health Organization Classification of Breast Tumors

Nektarios I Koufopoulos et al. Int J Mol Sci. .

Abstract

Breast carcinoma is the most common cancer in women. Nineteen different subtypes of breast carcinomas are recognized in the current WHO classification of breast tumors. Except for these subtypes, there are a number of carcinomas with special morphologic and immunohistochemical features that are not included in the 5th WHO classification, while others are considered special morphologic patterns of invasive breast carcinoma of no special type. In this manuscript, we systematically review the literature on four different subtypes of invasive breast carcinoma, namely lymphoepithelioma-like breast carcinoma, breast carcinoma with osteoclast-like giant cells, signet-ring breast carcinoma, and metaplastic breast carcinoma with melanocytic differentiation. We describe their clinicopathological characteristics, focusing on the differential diagnosis, treatment, and prognosis.

Keywords: breast carcinoma with osteoclast-like giant cells; lymphoepithelioma-like breast carcinoma; lymphoepithelioma-like carcinoma; metaplastic carcinoma; metaplastic carcinoma with melanocytic differentiation; signet-ring cell carcinoma.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA 2020 flowchart showing the search strategy, excluded studies, and finally included reports of lymphoepithelioma-like breast carcinomas.
Figure 2
Figure 2
PRISMA 2020 flowchart showing the search strategy, excluded studies, and finally included reports of breast carcinomas with osteoclast like giant cells.
Figure 3
Figure 3
PRISMA 2020 flowchart showing the search strategy, excluded studies, and finally included reports of signet-ring cell breast carcinomas.
Figure 4
Figure 4
PRISMA 2020 flowchart showing the search strategy, excluded studies, and finally included reports of metaplastic carcinomas with melanocytic differentiation.
Figure 5
Figure 5
(A) On low power examination, tumor cells are intimately admixed with a dense lymphoid stroma (Hematoxylin and Eosin, H&E; ×100); (B) On immunohistochemical examination, a immunopositivity in Cytokeratin AE1/AE3 demonstrates the epithelial nature of tumor cells (Cytokeratin AE1/AE3 mouse monoclonal AE1/AE3, Dako ×100) (original, previously unpublished photos).
Figure 6
Figure 6
(A) On low power examination, malignant epithelial cells are lying close to large multinucleated giant cells with abundant cytoplasm and numerous centrally located nuclei (Hematoxylin and Eosin, H&E; ×100); (B) On immunohistochemical examination CD68 (PGM1) immunostaining highlights the presence of osteoclast-like giant cells (CD68 mouse monoclonal PG-M1, Dako ×100) (original, previously unpublished photos).
Figure 7
Figure 7
(A) On medium power examination, tumor cells show a pure signet ring cell morphology with displacement of the cell nucleus (Hematoxylin and Eosin, H&E; ×200); (B) On immunohistochemical examination positive immunostaining for E-cadherin reveals the ductal nature of the carcinoma (E-cadherin mouse monoclonal NCH-38, Dako ×200) (original, previously unpublished photos).
Figure 8
Figure 8
Survival curves for the studied entities. Abbreviations: LELC: Lymphoepithelioma-like breast carcinoma; MBCMD: metaplastic breast carcinoma with melanocytic differentiation; BCOGC: breast carcinoma with osteoclast-like giant cells; SRCC: signet-ring cell carcinoma.
See this image and copyright information in PMC

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