Mammary metaplastic squamous cell carcinoma is an exceptionally rare and aggressive triple-negative breast cancer. Its propensity to mimic benign breast abscesses poses a significant diagnostic challenge, often leading to treatment delays. A 41-year-old Asian woman presented with a rapidly enlarging right breast mass, initially misdiagnosed and treated as an abscess at a local hospital. Definitive biopsy revealed triple-negative mammary metaplastic squamous cell carcinoma. The patient received neoadjuvant chemotherapy with a nab-paclitaxel, epirubicin, cyclophosphamide regimen. After an initial partial response observed in the first five cycles, the tumor exhibited progressive disease following the sixth cycle, a phenomenon potentially indicative of acquired chemoresistance. The patient subsequently underwent a modified radical mastectomy. Given the high-risk features and inspired by the SYSUCC-001 trial, adjuvant dose-dense capecitabine was administered postoperatively. No recurrence was detected during follow-up. This case highlights a classic diagnostic pitfall of mammary metaplastic squamous cell carcinoma masquerading as an abscess and illustrates a unique pattern of acquired resistance to a standard taxane-anthracycline neoadjuvant chemotherapy regimen. It underscores the need for heightened clinical vigilance. The potential benefit of adjuvant capecitabine for patients with high-risk mammary metaplastic squamous cell carcinoma observed here warrants further investigation.

Phyllodes tumors (PTs) are rare fibroepithelial breast tumors, albeit clinically significant. This study was implemented to investigate the immunohistochemical (IHC) expression of cyclin D1 in PT subtypes and in metaplastic spindle cell carcinoma. Fifty-three resected cases of PT subtypes were analyzed. IHC analysis assessed the percentage of positive stromal tumor cells and the intensity of cyclin D1 staining. The score was classified as either negative, low, or high positive. Statistical analysis was implemented to evaluate the outcomes. Significant variations in scores were observed among various subtypes of PT, with cyclin D1 exhibiting positive nuclear expression in the stromal component of borderline and malignant tumors ( P =0.001). Malignant PTs also showed significantly different cyclin D1 expression compared with triple-negative metaplastic spindle cell carcinoma ( P =0.028). Tumor recurrence was significantly associated with high cyclin D1 expression ( P =0.013). Receiver Operating Characteristic (ROC) curve analysis demonstrated moderate discriminatory ability, with an area under the curve (AUC) of 0.701 (95% CI: 0.535-0.856, P =0.023). Univariate analysis confirmed high cyclin D1 expression as a predictor of recurrence ( P =0.035). In conclusion, cyclin D1 overexpression provides insights into tumor progression and prognosis in PTs. Notably, positive cyclin D1 expression in metastatic malignant PT could be a diagnostic challenge, if not carefully considered within clinical context. Furthermore, the significant difference in cyclin D1 expression between malignant PT and triple-negative metaplastic spindle cell carcinoma highlights its potential utility in distinguishing between them.

Clinicopathologic Features of Metaplastic Breast Carcinoma: Experience from A Cancer Research Centre in India

Introduction: Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer, characterised by the lack of expression of Oestrogen Receptor (ER) Progesterone Receptor (PR) and Human Epidermal growth factor Receptor (HER2). TNBC is an aggressive type of invasive breast cancer. The clinical, histopathology, and immunohistochemistry study are vital in diagnosing TNBCs. TNBC have rarely been studied in relation to rare prevalence, diagnostic difficulties, and special histological variants. Aim: To study the clinicopathological profile of TNBC pateints. Materials and Methods: The present cross-sectional study, which included all the patients undergoing lumpectomy or modified radical mastectomy received in the the Surgical Pathology Section of tertiary care hospital and department of molecular biology and genetic laboratory, at Krishna Institute of Medical Sciences, Karad, Maharashtra, India from May 2019 to April 2021. During the study period, total of 302 specimens of modified radical mastectomy or lumpectomy that met the inclusion/exclusion criteria were received in the Surgical Pathology department were included in this study. All specimens were analysed using immunohistochemistry for ER, PR, and HER2 Neu expression. Out of these, 100 (33.1%) cases were negative for all three markers, reported as TNBCs. These 100 TNBC cases were evaluated based on the clinicopathological parameters such as patient age, tumour laterality, location, tumour size, histopathological type, histologic Grade, lymphovascular invasion and lymph nodal status of TNBCs and to analyse different histomorphological type. Results: In this total of 302 specimens of modified radical mastectomy, the Invasive Breast Carcinoma No Special Type (IBC NST) (82.70%, 250 out of 302 specimens) was the commonest histopathological diagnosis, followed by medullary carcinoma seven cases (7.0%), metaplastic carcinoma two cases (2.0%), invasive lobular carcinoma two cases (2.0%), one case of apocrine carcinoma (1.0%), one case of neuroendocrine carcinoma (1.0%) and one case of each (1.0%) as malignant phyllode’s tumour, mucinous carcinoma, etc. Conclusion: Prevalence of TNBC in India is considerably higher compared with that seen in Western populations. Present study included extensive analysis of breast cancer showing increasing in incidence of TNBC and is challenging to treat due to its adverse clinicopathological profile. The TNBC is associated with younger age, larger tumour size, higher histopathological Grades, extensive tumour necrosis, more regional lymph node metastasis, advanced stage at diagnosis and aggressive nature of tumour.

Spindle cell metaplastic carcinoma arising in breast phyllodes tumor: A challenging diagnosis with potential pitfalls

Abstract Metaplastic breast carcinoma (MBC) is a rare heterogeneous subtype of breast cancer, with limited data. Currently, it is treated according to the invasive breast cancer consensus guidelines, but it has a more distinct, aggressive biology and needs a more specific management. Our study aimed to evaluate the clinicopathological features, treatment response, and survival outcomes of our MBC patients treated with standard treatment modalities. We retrospectively analyzed clinicopathological characteristics, treatment, and survival outcomes of 20 patients diagnosed with MBC between 2012 and 2025. Twenty MBC patients were analyzed. The median age of presentation was 59.5 years. Fifty percent of patients had a clinical T3 tumor. Twenty percent had axillary lymph node involvement. Preoperative core biopsy was MBC in 40%. Most patients underwent mastectomy, and five patients underwent breast conservation surgery. Seventy-five percent had triple-negative receptor status. Of the 35% patients who received neoadjuvant chemotherapy (NACT), only one patient had a complete response. Adjuvant radiation was administered to 65%. Twenty percent received hormone therapy, and 5% received HER2-targeted therapy. At a median follow-up of 13.5 months (range: 3–72 months), 12 patients (60%) were alive with no evidence of disease, and eight patients (40%) died. Tumor recurrence was seen in five patients (25%). Overall survival (OS) at 1, 3, and 5 years was 84.4, 65.1, and 48.8%. Median OS was 55.2 ± 21.8 months. Recurrence-free survival was 64.7 ± 15.8 months. Statistically significant variable worsening the OS on univariate analysis was NACT (HR: 6.13, 95% CI: 1.09–34.46, p = 0.040). However, none of the variables were statistically significant by multivariate analysis. MBC is a rare and pathologically challenging diagnosis at core biopsy. Despite the large size at presentation, initial surgery should be preferred whenever feasible. Though lymph node metastasis is rare, when present, it has a worse prognosis.

Low-grade fibromatosis-like metaplastic breast carcinoma is a rare and challenging subtype of breast carcinoma due to its distinctive histological features mimicking a variety of lesions varying from benign to malignant, underscoring the importance of accurate diagnosis. We evaluated the clinicoradiological, histopathological features, and immunohistochemical profile of 11 low-grade fibromatosis-like metaplastic breast carcinoma patients diagnosed at our tertiary care center. Median age at diagnosis was 67 years (range 47-76 years) with a palpable breast lump of 1 to 2 years duration. Histologically, besides classical fibromatosis-like pattern, nodular growth was also noted (n = 2). Cytologically, spindle cell and stellate morphology were observed in 3 tumors each while rest of the tumors showed both features. Cellularity was minimal in 2, moderate in 8 and high in 1 tumor with mild to moderate nuclear atypia. Two tumors had small foci of infiltrative epithelial nests. Mixed inflammatory infiltrate was seen in all tumors. On immunohistochemistry, the tumor cells demonstrated positive staining for AE1/AE3, keratin 5/6, SMA, and p63, while negative for other markers. Details of initial treatment were available in 9 patients, of which 3 developed metastases. Low-grade fibromatosis-like metaplastic breast carcinoma is a rare and distinct subtype of metaplastic breast cancer with unique histological features and heterogeneity in morphology, posing diagnostic challenges and should be diagnosed after meticulous clinicopathological evaluation, comprehensive sampling and extensive immunohistochemistry panel.

Metaplastic breast carcinoma, a rare subtype(<1% of breast cancers), is typically triple-negative with a poor prognosis. The KEYNOTE-522 trial established pembrolizumab plus chemotherapy as a standard treatment for early-stage, high-risk triple-negative breast cancer. We report a case of metaplastic carcinoma with squamous differentiation achieving pathological complete response after neoadjuvant pembrolizumab-based chemoimmunotherapy. This case suggests that pembrolizumab-based chemoimmunotherapy may be a promising option for chemoresistant metaplastic carcinoma.

Special Subtypes of Triple Negative Breast Carcinoma.

Dual pathology breast carcinoma, whether unifocal, multifocal or multicentric may significantly impact patient prognosis. Certain histological combinations are associated with favourable outcomes, while others may indicate a more aggressive disease. We presented a report of two women with different pathological combinations. The first case had multicentric cancers of the left breast. She underwent neoadjuvant chemotherapy, then nipple-sparing mastectomy with axillary dissection and immediate transverse rectus abdominis myocutaneous (TRAM) breast reconstruction. Histopathological assessment revealed a combination of metaplastic carcinoma and invasive micropapillary carcinoma; both aggressive subtypes. Post adjuvant radiotherapy, she remained disease-free for five years. The second case had a unifocal right breast cancer managed with breast-conserving surgery and sentinel lymph node biopsy. Histopathology revealed a combination of invasive carcinoma of no special type (NST) and invasive papillary carcinoma. These subtypes are associated with a more favourable prognosis. Post radiotherapy and on endocrine therapy, this patient remains well at 2 years follow-up. These cases demonstrate the prognostic variability in dual histopathology breast cancers and highlights the importance of individualised treatment. Both patients remain disease free despite having dual pathology breast carcinoma which seem to suggest a more aggressive disease behaviour.

BackgroundBreast cancer is a heterogeneous disease with significant variation in clinical behaviour, pathological morphology and molecular patterns. While most of the breast cancer cases follow common histological and clinical patterns, but a few rare subtypes behave differently with a difference in prognosis and response to therapy. Recognizing these subtypes of breast cancer is important for accurate diagnosis and treatment planning.Aims and objectivesThis study aimed to evaluate the clinical features, pathological criteria, and outcomes of patients with these rare breast cancer subtypes treated at King Fahad Specialist Hospital (KFSH-D), a biggest regional tertiary care center. Patients and methodsThis is a retrospective, observational, descriptive study analyzing 30 patients diagnosed with rare breast cancer subtypes and treated at KFSH-D between January 2019 and December 2024.ResultsWe included 30 patients with rare pathological breast cancer subtypes. Among them, eight patients (27%) had apocrine carcinoma. The mean age at diagnosis for this group was between 55 and 60 years and a mean tumor size was greater than 2 cm. Additionally, 14 (46%) patients had metaplastic carcinoma, with a mean age at diagnosis of 45-60 years and tumor sizes ranging between 3 and 5 cm. Five (17%) patients were diagnosed with mucinous adenocarcinoma. Their mean age at diagnosis was 70 years, with tumors larger than 2 cm. All of these patients had stage N0-N1 disease and were positive for estrogen receptor (ER), progesterone receptor (PR), and negative for Her-2/neu on immunohistochemistry (IHC). One (3%) patient had lymphoepithelioma-like carcinoma. She was diagnosed at 51 years of age, with a tumor size of 2.2x3.2 cm. She underwent simple mastectomy and sentinel lymph node biopsy (SLNB). The tumor was histologic grade III with no lymphovascular invasion or intraductal component. We also identified two (7%) patients with invasive ductal carcinoma (IDC) showing neuroendocrine differentiation. Both were positive for chromogranin A and synaptophysin on IHC. Their ages at diagnosis were 55-65 years, and tumor sizes ranged from 4 to 6 cm. These tumors were histologic grade III, hormone receptor-positive, and Her-2/neu negative. Survival outcomes varied across groups, with mucinous carcinoma showing the most favorable prognosis.ConclusionRare subtypes of invasive breast cancers have distinct clinical and pathological behaviours with different outcomes. Recognition of these tumors will help in patient-tailored treatment strategies and will contribute to better patient management.

Pleomorphic adenoma of the breast is a rare tumor, with fewer than 100 patients described in the English literature, mainly as case reports and small case series. Histologically, breast pleomorphic adenoma resembles its more common salivary gland counterpart; however, it can present diagnostic challenges, particularly on core needle biopsy and fine-needle aspiration. The differential diagnosis includes benign and malignant tumors, which carry major treatment implications, from the extent of surgical intervention to the potential use of chemotherapy. Herein we describe a tumor that was initially diagnosed as a triple-negative matrix-producing metaplastic carcinoma, but a secondary review led to the diagnosis of pleomorphic adenoma of the breast. Prior to the secondary review, the patient underwent an excisional biopsy, sentinel lymph node biopsy, and one round of chemotherapy. This report adds to the limited literature surrounding this entity and discusses the differential diagnosis along with histopathologic and immunohistochemical findings that aid in the diagnosis and reviews the radiologic findings observed throughout the patient's clinical course. This patient underscores the difficulty of diagnosis and highlights the need for multidisciplinary consideration and communication to avoid overtreatment.

Background and Objectives: Low-grade triple-negative breast carcinomas (LG-TNBCs) represent a rare subset of breast cancers that deviate from the aggressive clinical course typically associated with triple-negative tumors. This narrative review aims to consolidate current knowledge on LG-TNBCs, highlighting their diagnostic features, molecular characteristics, and clinical implications to guide appropriate patient management and prevent overtreatment. Materials and Methods: We conducted a comprehensive narrative review using PubMed/MEDLINE, Embase, and Scopus databases up to September 2025. Search terms included combinations of "triple-negative breast carcinoma", "low-grade", "adenoid cystic carcinoma", "secretory carcinoma", "acinic cell carcinoma", "tall cell carcinoma with reversed polarity", "low-grade adenosquamous carcinoma", and "fibromatosis-like metaplastic carcinoma." Studies reporting clinicopathologic, immunohistochemical, or molecular data were included. Results: LG-TNBCs include seven distinct entities: adenoid cystic carcinoma, secretory carcinoma, acinic cell carcinoma, tall cell carcinoma with reversed polarity, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, and mucoepidermoid carcinoma. These neoplasms are characterized by distinct morphologic patterns, specific immunohistochemical profiles, and recurrent molecular alterations such as ETV6-NTRK3 fusions and MYB rearrangements. Despite their triple-negative immunoprofile, they demonstrate indolent clinical behavior with excellent prognosis and low metastatic potential, although local recurrence is reported in variants exhibiting infiltrative, locally aggressive behavior. Conclusions: Recognition of LG-TNBCs is essential to prevent overtreatment and guide personalized patient management. Molecular characterization provides diagnostic confirmation and therapeutic opportunities, particularly for NTRK-fusion-positive tumors treatable with targeted inhibitors, highlighting the importance of precision medicine in rare breast tumors.

Clinical Characteristics and Survival Outcomes of Metaplastic Breast Carcinoma Subtypes: A Retrospective Study.

Abstract Introduction/Objective Metaplastic breast carcinoma (MBC) is a rare subtype of triple-negative breast cancer with both epithelial and mesenchymal features, comprising less than 1% of all breast malignancies. Even rarer is the occurrence of MBC arising within a phyllodes tumor and presents significant diagnostic and therapeutic challenge. Methods/Case Report A 72-year-old female with a history of kidney and thyroid malignancies presented with right breast mass. Imaging revealed a 4.0x3.3x2.7 cm heterogeneously enhancing lesion in the upper central right breast. Ultrasound-guided core needle biopsy demonstrated a triple-negative, poorly differentiated ductal carcinoma with adenosquamous and spindle cell features, consistent with metaplastic carcinoma. The patient received neoadjuvant therapy, followed by right mastectomy. Histopathologic examination confirmed high-grade metaplastic carcinoma arising within a phyllodes tumor, with both spindle cell and squamous differentiation. Immunohistochemistry demonstrated strong positivity for p63, p40, CK5/6, and OSCAR in malignant epithelial/squamous components. GATA3 confirmed breast origin, S100 was focally positive. The spindle cell component expressed vimentin and BCL2. Ki-67 was elevated (30%) in the metaplastic components. Results NA Conclusion This rare case illustrates a highly unusual presentation of metaplastic breast carcinoma arising within a phyllodes tumor, underscoring the need for thorough histopathological and immunohistochemical evaluation to guide appropriate management. As such cases remain exceptionally rare, further studies are needed to clarify their behavior, prognosis, and treatment strategies.

Abstract Introduction/Objective Metaplastic carcinoma is an uncommon type of breast cancer, accounting for 0.2–1% of invasive breast malignancies. It is even rarer in transgender females. To our knowledge, this is the first reported case of metaplastic breast carcinoma in a transgender female. Methods/Case Report A 40-year-old transgender female on chronic estrogen, progesterone, and spironolactone therapy presented with a two-month history of a palpable left breast mass. Imaging revealed an 8 cm BI-RADS 4 lesion in the upper outer quadrant. Core needle biopsy showed a high-grade malignant neoplasm with a predominant spindle cell component and scattered vague glandular structures. Brisk mitotic activity was noted. Immunohistochemical stains revealed focal positivity for PanCK, CK5/6, and p63; diffuse strong vimentin positivity; ER-negative, PgR weakly positive (1%), HER2-negative, and Ki-67 at 90%. A final diagnosis of poorly differentiated malignant spindle cell tumor, favoring metaplastic carcinoma, was made. Despite the initiation of chemotherapy, the mass continued to grow in size. Additional stains showed rare EMA positivity, focal CD99 positivity, non-specific BCL-2 staining, and negativity for SMA, Desmin, and CD34. Results NA Conclusion Despite the rarity of metaplastic carcinoma diagnosis, it is necessary to be alert to this pathology in various cases to ensure timely and accurate diagnosis and treatment of the patient.

Abstract Introduction/Objective Gene expression profiling of human tumors has introduced a new approach for classifying breast cancers. Estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu (HER2) status provides crucial prognostic and predictive information for these patients. A project was designed to find the overall proportion of prognostic markers in breast carcinoma in our tertiary institution. Methods/Case Report In a retrospective study, breast specimens between January 1, 2024, and December 31, 2024, were evaluated. 233 specimens (132 biopsies, 101 lumpectomies/ mastectomies) had a diagnosis of invasive ductal carcinomas (n = 157), DCIS (n = 46), LCIS (n = 4), invasive lobular carcinomas (n = 15), metaplastic carcinomas (n = 6), mucinous carcinomas (n = 3) and pure tubular carcinomas (n = 2). They all had subsequent ER, PR, Her-2/Neu testing Results The overall proportion of ER-negative breast cancers (n = 31) was 13.3%. The majority of invasive carcinomas (79.6%, n = 137) had ER &amp;gt; 60% positivity. Out of all invasive carcinomas, 16.8% (n = 29) were triple negative. These were all invasive ductal grade 2-3/3 or metaplastic carcinoma. The overall proportion of HER2-positive breast cancers, tested by IHC or FISH, was 10.7% (n = 25). Conclusion Our findings correlate with the CAP benchmark which establishes that the proportion of ER-negative breast cancers should not exceed 30%, and that the overall proportion of HER2-positive breast cancers is 10 to 25%.

Abstract Introduction/Objective Microglandular adenosis (MGA) of the breast is an uncommon lesion characterized by a benign course. However atypical MGA (AMGA) and MGA-associated carcinoma have been described, suggesting that MGA may represent a non-obligate precursor of carcinoma. We report five cases of MGA-associated breast carcinoma and describe the key pathological features of this entity. Methods/Case Report Five cases of MGA-associated breast carcinoma were identified. Clinical data, histologic and immunohistochemical characteristics were reviewed and analyzed. Results All cases involved women with ages ranging 48 to 75 with a median of 70. Four of five cases demonstrated invasive carcinoma, while one case showed ductal carcinoma in-situ (DCIS). Invasive carcinomas encompassed various histologic types: metaplastic carcinoma with chondromyxoid matrix production (2 cases), invasive carcinoma with secretory features (1 case), and invasive carcinoma of no special type (ductal) (1 case). A morphologic transition from MGA to AMGA to carcinoma was observed in all cases. S100 was consistently positive in all cases. Myoepithelial markers demonstrated the absence of myoepithelial cells in the invasive carcinoma as well as MGA / AMGA component. Conclusion This series highlights the histologic spectrum and key diagnostic features of MGA-associated carcinoma. Awareness of this entity is crucial for appropriate diagnosis and clinical management.

Abstract Introduction/Objective Low grade Adenosquamous Carcinoma (LGASC) is a rare subtype of metaplastic breast carcinoma (MBC). In contrast to the typical aggressive nature of MBC, LGASC is an indolent tumor with favorable outcome. It often poses a diagnostic dilemma due its non-specific histology and immunophenotype. LGASC are typically triple-negative. We report a rare case of LGASC showing estrogen receptor (ER) positivity. Methods/Case Report 59-year-old female was found to have 0.6 cm irregular hypoechoic breast mass on screening mammogram. The biopsy revealed infiltrative and angulated tubules lined by cytologically bland epithelial cells within desmoplastic appearing stroma. Foci of squamous cell nests were present, highlighted by immunohistochemical staining with p63. The tubules were highlighted by CK5/6 and showed focal loss of p63 staining. The histologic features in conjunction with immunophenotype were consistent with LGASC. Notably, the tumor showed weak focal expression of ER. Progesterone receptor and HER2 were negative. The patient underwent localized lumpectomy, and she remains free of recurrence 3-years after the diagnosis. Results NA Conclusion LGASC is a rare variant of MBC with excellent prognosis. ER expression in LGASC is infrequent. Careful pathological analysis is required to diagnose this entity, due to its resemblances with both benign and malignant lesions of the breast.

Abstract Introduction/Objective Endometrial carcinosarcoma (ECS) is a rare but highly aggressive metaplastic carcinoma known for its molecular heterogeneity. The incidence of ECS has been increasing in the South Gulf Coast region. This study aimed to characterize the molecular heterogeneity related to tumor morphology in patients diagnosed with ECS in this region. Methods/Case Report Thirty-one patients diagnosed with ECS between 2018 and 2023 were retrospectively evaluated. The analysis included patient ethnicity, age, BMI, tumor histology, staging, mismatch repair status, and genetic alterations. Staging was performed according to the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system. Treatment outcomes were correlated with clinicopathological features and management strategies. Kaplan-Meier survival analysis was used to determine the impact of various clinicopathological variables on disease-free survival (DFS) and overall survival (OS). Molecular data and genetic alterations from CARIS reports were compared to The Cancer Genome Atlas (TCGA) dataset. Results The most affected ethnic group was Black or African American (52%), followed by White (41%) and Latino (7%) patients. Older age and obesity were associated with a higher incidence of ECS. Notably, deep myometrial tumor invasion was less common, while rhabdomyosarcoma and heterologous sarcoma were more frequent in the study population compared to general reports. Early-stage patients (pT1aN0, pT1bN0) had better survival outcomes than those with advanced stages (pT3aN1a). However, recurrence was frequent (35%), even among early-stage patients. TP53 mutations were more commonly observed in early-stage tumors, while ARID1A mutations were more frequent in advanced-stage cases. No co-occurrence of TP53 and ARID1A mutations was detected. Tumors harboring PTEN, KRAS, and ARID1A mutations were associated with higher FIGO stages compared to those with TP53, FBXW7, and PP2R1A mutations, which contrasts with the data derived from the TCGA. Conclusion This study highlights the relationship between advancing age and obesity with increasing incidence of ECS in the South Gulf Coast region. The molecular profile of ECS in this population differs from that observed in broader datasets. The higher frequency of ARID1A mutations in advanced-stage tumors, compared to TP53 mutations in early-stage cases, suggests potential molecular drivers that could guide future therapeutic strategies.