{"paper_id":"2c852c27-0bf1-4fd3-94fa-86a4c4c2a778","body_text":"Review began\n 09/18/2025 \nReview ended\n 10/05/2025 \nPublished\n 10/08/2025\n© Copyright \n2025\nYagyu et al. This is an open access article\ndistributed under the terms of the Creative\nCommons Attribution License CC-BY 4.0.,\nwhich permits unrestricted use, distribution,\nand reproduction in any medium, provided\nthe original author and source are credited.\nDOI:\n 10.7759/cureus.94088\nThe Diagnostic Pitfalls of Invasive Breast Lobular\nCarcinomas Around Involuting Fibroadenomas\nWith Coarse Calcifications: A Case Report\nTaisuke Yagyu \n, \nShoji Oura \n1.\n Department of Surgery, Kishiwada Tokushukai Hospital, Kishiwada, JPN\nCorresponding author: \nShoji Oura, \nshouji.oura@tokushukai.jp\nAbstract\nA 69-year-old female with an involuting fibroadenoma (FA) was referred to our hospital for detailed\nexamination of mammographic abnormalities around the coarse calcifications. Despite the lack of\nmeaningful findings on medio-lateral oblique (MLO) view mammography, cranio-caudal (CC) view\nmammography showed spiculae around the calcifications. Ultrasound showed an oval mass with indistinct\nmargins, disruption of the anterior borders of the mammary gland, and haloes just above the disruption\nareas. MRI depicted an irregular mass that showed low signals on T1-weighted images, slightly high signals\non fat-suppressed T2-weighted images, and a plateau pattern on dynamic studies. Under the tentative\ndiagnosis of breast cancer around the calcified FA, we performed a vacuum-assisted biopsy of the target\nlesion.\nPathological examination showed small atypical cells growing in linear and scattered fashions with\nconnective tissue proliferation, leading to the diagnosis of invasive lobular carcinoma (ILC). The patient,\ntherefore, underwent nipple sparing mastectomy and sentinel node biopsy followed by immediate breast\nreconstruction using the extended latissimus dorsi musculocutaneous flap. Postoperative pathological study\nrevealed four ILC foci up to 18 mm in size around the intracanalicular type FA with massive calcifications.\nImmunostaining showed estrogen and progesterone receptor positivity (both Allred score 8), human\nepidermal growth factor receptor type 2 negativity, and a Ki-67 labelling index of 5%. The patient recovered\nuneventfully, was discharged on the 14th day after the operation, and is scheduled for long-term outpatient\nfollow-up on endocrine therapy. Diagnostic physicians should note that ILCs can develop around the\ncalcified FAs and are prone to being overlooked on MLO view mammography.\nCategories:\n Other, Radiology, Oncology\nKeywords:\n breast cancer, coarse calcification, fibroadenoma, invasive lobular carcinoma, medio-lateral view\nmammography\nIntroduction\nInvasive lobular carcinomas (ILCs) naturally develop from mammary lobules. They can be multicentric and\nbilateral, and characteristically metastasize to rare organs and sites such as the gastrointestinal tract and\nretroperitoneum \n[1,2]\n. ILCs generally have abundant fibrous components, which can cause distortion of the\nmammary gland and give ILCs a hardness. Scirrhous-type invasive ductal carcinomas also have a large\namount of fibrous components, often leading to challenges in terms of differential diagnosis between\nscirrhous carcinomas and ILCs, not only pathologically but also radiologically. Scirrhous-type invasive\nductal carcinomas, however, less often have multicentricity and bilaterality, and rarely develop distant\nmetastasis to uncommon organs and tissues.\nFibroadenomas (FA) have both epithelial and connective tissue components and are the most common\nbenign breast tumors. Despite the known frequent harboring of MED12 mutations \n[3]\n, i.e., a gene encoding\npart of the RNA polymerase II mediator complex found in more than half of uterine myomas, the exact\npathogenesis of FA remains unknown. Fibroadenomas grow in an estrogen-dependent manner and,\ntherefore, do not grow larger after menopause, and frequently develop coarse calcifications \n[4]\n. Similar to\nILCs, fibroadenomas develop from mammary lobules. Nevertheless, it is rare for breast cancer to develop\nwithin fibroadenomas, and when it does, it is most often ductal carcinoma in situ \n[5]\n. No studies, however,\nhave reported a lobular carcinoma encompassing a calcified FA to date. We report a case of ILC surrounding\na calcified fibroadenoma, which had obscured the ILC.\nCase Presentation\nA 69-year-old female with no particular medical history, whose mother had a history of pancreatic cancer,\nhad been aware of a benign tumor in her left breast for more than 20 years. She was referred to our hospital\ndue to the abnormal mammography findings around the benign tumor. Mammography showed a dense\nbreast pattern and no abnormalities except for the coarse calcifications on the medio-lateral oblique (MLO)\nview. Cranio-caudal (CC) view mammography, however, showed spiculae around the calcifications (Figure\n1\n1\n \nOpen Access Case Report\nHow to cite this article\nYagyu T, Oura S (October 08, 2025) The Diagnostic Pitfalls of Invasive Breast Lobular Carcinomas Around Involuting Fibroadenomas With Coarse\nCalcifications: A Case Report. Cureus 17(10): e94088. \nDOI 10.7759/cureus.94088\n\n1\n).\nFIGURE\n 1: Mammography findings\n(A) Medio-lateral oblique view mammography only showed coarse calcifications (arrow). (B) Cranio-caudal view\nmammography showed evident distortion (arrows) around the calcifications\nUltrasound showed an oval mass, 18 mm in size, with indistinct margins, disruption of the anterior borders\nof the mammary gland, and haloes just above the disruption areas (Figure \n2\n).\n \n2025 Yagyu et al. Cureus 17(10): e94088. DOI 10.7759/cureus.94088\n2\n of \n6\n\nFIGURE\n 2: Ultrasound findings\nUltrasound showed an oval mass (asterisk) with indistinct margins, internal low echoes, attenuated posterior\nechoes (open circle), disruption of mammary gland anterior borders (arrows), and focal haloes (arrowhead)\nMRI depicted an irregular mass that showed low signals on T1-weighted images, slightly high signals on fat-\nsuppressed T2-weighted images, and a plateau pattern on dynamic studies (Figure \n3\n).\n \n2025 Yagyu et al. Cureus 17(10): e94088. DOI 10.7759/cureus.94088\n3\n of \n6\n\nFIGURE\n 3: MRI findings\nMRI of the mass showed low signals (arrows) on T1-weighted images (A), faint high signals (arrows) on T2-\nweighted images (B), and early (C) and retained (D) enhancement (arrows) on dynamic studies\nMRI: magnetic resonance imaging\nUnder the tentative diagnosis of breast cancer around the calcified FA, we performed a vacuum-assisted\nbiopsy of the target lesion. Pathological examination showed small atypical cells growing in linear and\nscattered fashions with connective tissue proliferation, leading to the diagnosis of ILC. Immunostaining\nshowed that the ILC was a luminal subtype breast cancer with a low proliferating index. Based on the\npatient's wishes, we operate on the patient with nipple sparing mastectomy and sentinel node biopsy,\nfollowed by immediate breast reconstruction using the extended latissimus dorsi musculocutaneous flap.\nPostoperative pathological study revealed four ILC foci up to 18 mm in size and an intracanalicular type FA\nwith massive calcifications. Immunostaining showed estrogen and progesterone receptor positivity (both\nwith an Allred score of 8), human epidermal growth factor receptor type 2 negativity, and a low Ki-67\nlabelling index of 5% (Figure \n4\n).\n \n2025 Yagyu et al. Cureus 17(10): e94088. DOI 10.7759/cureus.94088\n4\n of \n6\n\nFIGURE\n 4: Pathological findings\n(A) Low magnified view showed invasive lobular carcinoma cells (closed areas) and the involuting fibroadenoma\n(asterisk) (H.E. ×4). (B) Magnified view showed atypical cells growing in linear (arrow) and cord-like (arrowheads)\nfashions against the abundant fibrous backgrounds (H.E. ×200). (C) Fibroadenoma (arrows) was of an\nintracanalicular phenotype (H.E. ×40). (D) Atypical cells (arrows) surrounded the coarse calcifications (asterisk)\n(H.E. ×40). (E) Immunostaining showed that invasive lobular carcinoma cells (brownish cells) had high estrogen\nreceptor positivity (×200). (F) Immunostaining showed that invasive lobular carcinoma cells (brownish cells) had\nhigh progesterone receptor positivity (×200). (G) Tumor cells showed no positivity of human epidermal growth\nfactor receptor on immunostaining (×200). (H) Tumor cells had a low Ki-67 labelling index of 5% (×200)\nThe patient recovered uneventfully; she was discharged on the 14th day after the operation and is scheduled\nfor a 10-year outpatient follow-up on endocrine therapy.\nDiscussion\nCoarse calcifications observed in this case could be either dystrophic calcifications or those developed in\npostmenopausal involuting fibroadenomas. Dystrophic calcifications can develop through various\nmechanisms, such as surgery to the breast and degenerative changes of the mammary gland. Especially,\nbreast surgery can cause spiculae around the operative site, which often mimic breast cancer-induced\nspiculae. Coarse calcifications after breast surgery, however, are generally accompanied by evident surgery-\nrelated ultrasound findings and, therefore, were easily negated in this case. Coarse calcifications are\nnaturally composed of calcium. Large calcifications have such high acoustic impedance that they reflect\nalmost all ultrasound waves, preventing the diagnostic physicians from properly evaluating the tissue under\nthe large calcifications on ultrasound. On the other hand, calcifications have a high X-ray attenuation\ncoefficient on mammography, showing them as white and making small lesions in front of or behind them,\nand are often overlooked, like in this case.\nUnlike pleomorphic ILCs \n[6]\n, classic ILCs generally have better clinical outcomes than invasive ductal\ncarcinomas \n[7]\n. In fact, the Ki67 labelling index was very low at 5% in this case. Due to the lack of detailed\ninformation about our patient's past screening mammography, we could not evaluate how coarse\ncalcifications had obscured this less aggressive ILC. However, it cannot be denied that the Japanese standard\nscreening mammography method, i.e., MLO view mammography without CC view mammography for\npatients aged 50 years or older \n[8]\n, might have led to the underdetection of ILC in this case.\nIt is well known that MLO view mammography shows the breast in a more expanded form than CC view\nmammography. Many diagnostic physicians, however, have empirically known that the ILCs are more clearly\nvisualized on CC view mammography than on MLO view mammography. Unfortunately, no research has\nproved to date why this phenomenon occurs. Clear tumor margins may be obscured by overlapping with the\nmammary gland and can often become evident by increased breast compression.\nWe have already clarified that fibrous components, when present at the mass borders mixed with cancer\ncells, can obscure tumor margins \n[9,10]\n. ILCs, therefore, have highly indistinct margins, which never become\ndistinct with more breast compression. Conversely, when tumor margins show spicula-like structures, they\nbecome more unclear on the MLO view mammography due to the further magnification of unclear margins.\nIn addition, the breasts are thinner on the MLO view mammography than on the CC view mammography,\nand make the mass opacity further lower, leading to more difficult identification of ILCs on MLO view\nmammography. These are presumably the main reasons why ILCs are less detectable on MLO view\nmammography.\nSimple fibroadenomas are not known to increase the risk of breast cancer \n[11]\n. The clinical significance of\nwhy this ILC developed just around the calcified fibroadenoma is unclear. However, it is imperative that\nscreening mammography with MLO and CC views be performed even for elderly people to avoid\nunderdetection of ILCs around the coarse calcifications, if present.\n \n2025 Yagyu et al. Cureus 17(10): e94088. DOI 10.7759/cureus.94088\n5\n of \n6\n\nConclusions\nClassic-type ILCs surrounding calcified fibroadenomas are extremely rare and can be overlooked on\nscreening mammography. Therefore, if known calcified fibroadenomas are present, screening\nmammography should be performed by using both MLO and CC views, even for elderly people. In addition,\ndiagnostic physicians should note that ILCs can be detected more easily on CC view mammography than\nMLO view mammography.\nAdditional Information\nAuthor Contributions\nAll authors have reviewed the final version to be published and agreed to be accountable for all aspects of the\nwork.\nConcept and design:\n  \nShoji Oura, Taisuke Yagyu\nAcquisition, analysis, or interpretation of data:\n  \nShoji Oura, Taisuke Yagyu\nDrafting of the manuscript:\n  \nShoji Oura, Taisuke Yagyu\nCritical review of the manuscript for important intellectual content:\n  \nShoji Oura, Taisuke Yagyu\nSupervision:\n  \nShoji Oura, Taisuke Yagyu\nDisclosures\nHuman subjects:\n Informed consent for treatment and open access publication was obtained or waived by all\nparticipants in this study. \nConflicts of interest:\n In compliance with the ICMJE uniform disclosure form, all\nauthors declare the following: \nPayment/services info:\n All authors have declared that no financial support\nwas received from any organization for the submitted work. \nFinancial relationships:\n All authors have\ndeclared that they have no financial relationships at present or within the previous three years with any\norganizations that might have an interest in the submitted work. \nOther relationships:\n All authors have\ndeclared that there are no other relationships or activities that could appear to have influenced the\nsubmitted work.\nReferences\n1\n. \nOrvieto E, Maiorano E, Bottiglieri L, et al.: \nClinicopathologic characteristics of invasive lobular carcinoma of\nthe breast: results of an analysis of 530 cases from a single institution\n. 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