Radiological and Pathological Challenges in Diagnosing Pleomorphic Lobular Carcinoma In Situ With Focal Invasion: A Case Report

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Abstract

INTRODUCTION

Lobular neoplasia, which comprises atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), is characterized by the proliferation of uniform, discohesive epithelial cells within the terminal duct-lobular unit. LCIS is further subdivided into classical LCIS (CLCIS), pleomorphic LCIS (PLCIS), and florid LCIS (FLCIS) [1]. Distinguishing these subtypes is clinically significant as it directly influences management decisions. ALH and CLCIS are typically managed with surveillance, whereas PLCIS and FLCIS often require surgical excision because of their elevated malignancy risk [2].

PLCIS is particularly notable for its high-grade nuclear atypia, granular eosinophilic cytoplasm, and frequent comedonecrosis and microcalcifications [3]. These features closely resemble those of high-grade ductal carcinoma in situ (DCIS), complicating the differentiation between the two entities in both histopathological and radiological assessments [3]. Accurate identification of PLCIS is critical, considering its significant potential to progress to invasive carcinoma and the associated risk of breast cancer [4,5].

This case report describes a rare presentation of PLCIS manifesting as a mass with concurrent microcalcifications mimicking invasive ductal carcinoma (IDC). This atypical presentation underscores the diagnostic complexities associated with PLCIS and emphasizes the importance of thorough pathological and radiological evaluations to guide optimal management strategies.

CASE REPORT

A 44-year-old woman presented to a local breast clinic with a 1-year history of a palpable mass in her right breast. Initial ultrasonography revealed an irregular hypoechoic mass with echogenic foci indicative of microcalcifications and increased internal vascularity. An ultrasound-guided core-needle biopsy confirmed the diagnosis of infiltrating ductal carcinoma. The patient was then referred to our institution for further management and treatment.

On physical examination, a mass approximately 4 cm in size was palpated in the right upper outer breast quadrant. Bilateral mammography revealed an irregular 4 cm mass with fine pleomorphic microcalcifications in the right upper outer breast quadrant (Figure 1A). Ultrasound imaging revealed an irregular, indistinct, and hypoechoic mass with densely packed microcalcifications (Figure 1B). Further evaluation using breast magnetic resonance imaging showed an approximately 4 cm irregular, heterogeneous, enhancing mass with a washout kinetic pattern in the right upper outer breast (Figure 1C). Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed hypermetabolism of the breast mass with a maximum standardized uptake value of 9.3, with no evidence of abnormal hypermetabolism elsewhere (Figure 1D). The patient underwent breast-conserving surgery with a sentinel lymph node biopsy. Gross examination revealed a whitish-yellow mass measuring 4.2× 4.0 × 2.2 cm (Figure 2A). Histopathological analysis illustrated marked distension of the acini owing to discohesive cellular proliferation, significant nuclear pleomorphism, and areas of comedonecrosis and calcification. Thus, PLCIS was diagnosed measuring 42 mm (Figure 2B, C). In addition, a coexisting invasive lobular carcinoma (ILC) measuring 1.04 mm was identified, with immunohistochemistry analysis determining that the carcinoma cells were positive for estrogen and progesterone receptors but negative for human epidermal growth factor receptor 2/neu and E-cadherin (Figure 2D). Sentinel lymph node biopsy showed no evidence of metastasis. Post-operatively, the patient received adjuvant radiation and hormone therapy. At the 72-month follow-up, no evidence of disease recurrence was observed. This case was approved by the Institutional Review Board (IRB) of Chonnam National University Hwasun Hospital (IRB No. CNUHH-2024–0165) and informed consent was waived by the IRB because this was a retrospective study.

Figure 1.

Radiological characteristics of pleomorphic lobular carcinoma in situ concurrent with invasive lobular carcinoma. (A) The mediolateral oblique mammographic view demonstrates an irregular mass with fine pleomorphic microcalcifications (arrows) located in the upper outer quadrant of the right breast. (B) Ultrasound image reveals an irregular, indistinct hypoechoic mass (arrow) with densely packed echogenic reflectors, suggestive of microcalcifications. (C) Axial contrast-enhanced T1-weighted fat-suppressed subtraction magnetic resonance image displays a 4-cm irregular, heterogeneously enhancing mass (arrow) in the upper outer quadrant of the right breast. (D) Axial positron emission tomography/computed tomography scan exhibits markedly increased fluorodeoxyglucose uptake (maximum standardized uptake value=9.3), indicating hypermetabolic activity within the lesion.

Figure 2.

Histopathological examination of pleomorphic lobular carcinoma in situ concurrent with invasive lobular carcinoma. (A) Gross specimen of the excised breast mass demonstrates a well-circumscribed, whitish-yellow lesion measuring approximately 4.2 cm. (B) Photomicrograph of histopathologic specimen shows a mass measuring approximately 4.2 cm, characterized by significant distention of the acini filled with cellular proliferation (H&E stain: original magnification, ×5). (C) Photomicrograph of histopathologic specimen illustrates expanded acini occupied by a pleomorphic proliferation of discohesive cells with central necrosis and calcifications (H&E stain: original magnification, ×200). (D) Photomicrograph identifies estrogen receptor-positive invasive lobular carcinoma component measuring 1.04 mm within pleomorphic lobular carcinoma in situ. The tumor shows negative E-cadherin staining (Inlet: Magnified view of E-cadherin negativity).

DISCUSSION

A lesion, initially identified as a mass with suspicious calcifications, was misdiagnosed as IDC based on core-needle biopsy findings. However, subsequent surgical resection revealed this lesion to be PLCIS, with a minor component of ILC, measuring only 1.04 mm. This case underscores the diagnostic complexities and challenges inherent in managing various forms of LCIS and emphasizes the instrumental role of comprehensive pathological and radiological correlations.

The initial misdiagnosis based on core-needle biopsy is attributed to several factors. Notably, biopsy specimens from an outside clinic did not include immunohistochemical staining results, which are essential for distinguishing PLCIS from high-grade DCIS. In particular, the absence of E-cadherin is a notable distinguishing marker for differentiating between DCIS and LCIS, as LCIS and ILC are negative for E-cadherin in approximately 80%–90% of cases [1]. PLCIS shares several histopathological features with high-grade DCIS including nuclear pleomorphism, comedonecrosis, and calcification, which can cause diagnostic confusion. Considering the diagnostic overlap between PLCIS and DCIS, incorporating immunohistochemical staining into preoperative biopsies is essential for misdiagnosis prevention and guiding of appropriate treatment strategies. Furthermore, the routine review of biopsy slides by a specialized pathology department improved the diagnostic accuracy and reduced discrepancies. Moreover, core-needle biopsy has inherent limitations, including sampling errors and the inability to capture the complete lesion, potentially resulting in overestimation or pathology misinterpretation [6]. Misdiagnosis of PLCIS as IDC may lead to overtreatment, such as complete excision with wide margins or axillary sentinel node biopsy, and provide inaccurate prognostic information. Thus, an accurate diagnosis is crucial for appropriate management and avoiding the potential morbidity associated with overtreatment.

This study also emphasized that PLCIS may exhibit imaging characteristics that can be mistaken for malignancy, thereby warranting more aggressive interventions. The most frequent radiological finding in PLCIS is abnormal microcalcification [7,8]. Reports of LCIS presenting as a mass are rare in the literature [9-12]. Herein, mammography and ultrasonography revealed an irregular 4 cm mass with fine pleomorphic microcalcifications, and PET/CT demonstrated increased FDG uptake, which is consistent with IDC. To the best of our knowledge, this case is the first to document PET/CT findings in PLCIS, making this case particularly significant due to its rarity and complexity. A nuanced understanding of imaging features variability, PLCIS nature, and importance of accurate sampling of the targeted lesion is essential for the accurate management of this heterogeneous entity.

PLCIS management remains a subject of significant debatable. Current guidelines advocate for surgical excision of PLCIS owing to its potential to progress to invasive disease, following a core-needle biopsy diagnosis [13,14]; however, upgrade rates vary, partly due to the limited number of published cases and rarity of biopsy-diagnosed LCIS [14,15]. Herein, a 1.04 mm ILC was detected within a 4.2 cm PLCIS, suggesting that PLCIS may serve as a risk factor and precursor to ILC. Notably, the associated invasive component manifests as a classic or pleomorphic subtype of ILC or, less commonly, IDC [14]. As PLCIS acts as both a risk factor for developing invasive cancer and nonobligate precursor, further research is warranted to clarify its natural history and optimal treatment thresholds.

In conclusion, this case highlights the diagnostic complexities and clinical significance of PLCIS management. The uncommon presentation of a palpable mass with microcalcifications and risk of misdiagnosis, highlights the critical need for a meticulous and accurate diagnostic evaluation to guide the implementation of evidence-based management strategies.

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