AIMS: To objectively evaluate the prevalence of histological border irregularities in fibroadenomas (FAs) and characterise their association with specimen type, histological subtypes, prior procedures and associated path...AIMS: To objectively evaluate the prevalence of histological border irregularities in fibroadenomas (FAs) and characterise their association with specimen type, histological subtypes, prior procedures and associated pathologies. METHODS: A retrospective review of 912 FA specimens (549 core needle biopsies (CNBs), 45 vacuum-assisted biopsies (VABs), 242 excisions and 76 mastectomies) from 816 lesions was conducted. An irregular border was defined as an interface between the FA and adjacent parenchyma that was not smooth or circumscribed. Statistical analyses were performed to identify factors associated with irregularities in the FA contours. RESULTS: Border irregularity was present in 20.6% (188/912) of specimens. Prevalence was significantly lower in CNB (8.4%) compared with VAB (31.1%), mastectomy (34.2%) and excision (42.1%). By subtype, irregularity was most frequent in myxoid (41.7%), cellular (35.8%) and hyalinised (28.9%) FAs, compared with complex (20.4%), usual (16.2%) and juvenile (13.3%) forms. Calcifications, carcinoma in situ and invasive carcinoma, occurring within FAs, were associated with increased frequency of irregular borders. In multivariable analysis, a history of prior procedure was the strongest independent predictor of irregularity (OR 3.69, p<0.001). We found 1.6%, 2.5% and 0.2% of FAs to be accompanied by atypical hyperplasia, carcinoma in situ and invasive carcinoma, respectively. CONCLUSIONS: While FAs are conventionally described as possessing circumscribed contours, our study found irregular borders in approximately one in five specimens. This feature is significantly associated with prior clinical procedures, specific histological subtypes and certain concurrent pathologies. It is essential to recognise that an irregular border in fibroepithelial lesions can be encountered in FAs and is not exclusive to phyllodes tumours.
AIMS: Although acute myeloid leukaemia (AML), myelodysplasia-related (AML-MR), can be defined solely by molecular abnormalities, legacy studies did not analyse the gene. The -partial tandem duplication (-PTD) is describ...AIMS: Although acute myeloid leukaemia (AML), myelodysplasia-related (AML-MR), can be defined solely by molecular abnormalities, legacy studies did not analyse the gene. The -partial tandem duplication (-PTD) is described in myelodysplastic neoplasms (MDS) as well as AML. We describe the clinical, morphological, immunophenotypic and molecular features of AML harbouring PTD. METHODS: We studied 802 adult AML patients, for whom next-generation sequencing- based mutation and copy number analysis were available. For the patients harbouring -PTD, the immunophenotypic analysis including measurable residual disease (MRD), mutational landscape and the patient outcomes were analysed. RESULTS: We identified 45 patients of de novo and secondary AML harbouring -PTD. Morphological dysplasia and immunophenotypic abnormalities, described in MDS, were observed in 35.6% and 40% of de novo cases respectively. Furthermore, 44% of AML with -PTD could be diagnosed as AML-MR based on cytogenetics or genomics. We observed progenitor abnormalities, commonly aberrant CD7 (33%) and CD15 (59%), and granulocytic abnormalities like loss of side scatter (50%), asynchronous maturation patterns and loss of CD177 in mature granulocytes. Frequent mutations involving (30% of which were R172), (32% each), (29%), and (24% each) were noted. We also found that more than 25% of patients did not achieve morphological remission, and the remaining 60% were MRD positive. The outcomes of AML with -PTD with or without MR-associated abnormalities were similar. CONCLUSIONS: AML harbouring -PTD frequently displays MR immunophenotypic abnormalities and is frequently associated with AML-MR type mutations. In addition, they have similar outcomes as compared with AML-MR.
Rungjirajittranon T, Ponvilawan B, Sukpanichnant S
… +1 more, Owattanapanich W
J Clin Pathol
· 2026 Apr · PMID 41781199
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AIMS: Chronic myelomonocytic leukaemia (CMML) is a rare overlap syndrome between myelodysplastic neoplasms and myeloproliferative neoplasms. One distinct associated condition is systemic inflammatory and autoimmune disor...AIMS: Chronic myelomonocytic leukaemia (CMML) is a rare overlap syndrome between myelodysplastic neoplasms and myeloproliferative neoplasms. One distinct associated condition is systemic inflammatory and autoimmune disorders (SIADs). METHODS: We conducted a retrospective cohort study of newly diagnosed CMML patients at our institution between January 2006 and December 2020, comparing those with and without SIADs. Clinical characteristics, laboratory findings, molecular profiles, survival outcomes and leukaemic transformation rates were analysed. RESULTS: A total of 108 patients were included, of whom 26.9% had SIADs. Immune cytopenia was the most common SIAD, with 51.7% diagnosed concurrently with CMML. Most patients (93.5%) were classified as CMML-1, and 61.1% had the myeloproliferative phenotype. The most frequent mutation was (25.0%). Patients with SIADs showed a trend toward lower frequencies of (p=0.078) and (p=0.080) mutations. The median overall survival (OS) was 14.1 months, with a 1-year survival rate of 54%. The 1-year cumulative incidence of leukaemic transformation was 19.3%, and the 1-year leukaemia-free survival (LFS) rate was 49%. Patients with SIADs showed a trend towards longer OS (32.7 vs 9.9 months; p=0.058) and a significantly better LFS (32.7 vs 8.1 months; p=0.017). After adjusting for and mutations and haemoglobin <10 g/dL, SIADs remained protective against leukaemic transformation (HR, 0.13; p=0.038). CONCLUSIONS: SIADs occur in a substantial subset of CMML patients and are associated with significantly better LFS and reduced risk of leukaemic transformation, with a trend towards improved OS. TRIAL REGISTRATION NUMBER: TCTR20210810003.
Bedell M, da Silva EM, Selenica P
… +10 more, Gazzo AM, Blanco Heredia J, Basili T, Elishaev E, Harinath L, Diego E, Tageja N, Weigelt B, Reis-Filho JS, Bhargava R
J Clin Pathol
· 2026 Apr · PMID 41775529
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AIMS: A subset of microglandular adenosis (MGA) displays protein expression and molecular genetic alterations similar to those of synchronous triple-negative breast carcinoma (TNBC), supporting the hypothesis that MGA is...AIMS: A subset of microglandular adenosis (MGA) displays protein expression and molecular genetic alterations similar to those of synchronous triple-negative breast carcinoma (TNBC), supporting the hypothesis that MGA is a non-obligate precursor lesion to a subset of breast carcinomas. Here, we further explore this association in the context of genomic instability. METHODS: We use whole-genome sequencing to investigate the genetic landscape of two unusual cases of MGA associated with carcinoma in the setting of two distinct varieties of genomic instability. RESULTS: The first case describes a patient with Lynch Syndrome developing a low-grade TNBC of the left breast with adenoid cystic-like and MGA-like growth patterns and a contralateral, right breast MGA. Both carcinoma and contralateral MGA showed loss of MSH2 and MSH6 proteins. Molecular studies identified somatic hotspot mutation only in carcinoma. A germline mutation was detected in all samples, and somatic pathogenic mutation was detected only in carcinoma components, while the contralateral MGA displayed loss-of-heterozygosity of the wild-type allele, indicating distinct mechanisms of biallelic inactivation of between the samples. The second case consists of atypical MGA and associated high-grade TNBC arising in a setting of homologous recombination deficiency (HRD) with molecular signatures suggestive of -like/HRD-associated mutational features in addition to shared alterations. CONCLUSIONS: Genomic instability, either due to mismatch repair protein deficiency or due to HRD, may play a role in MGA, MGA-associated carcinogenesis and distinct morphological patterns.
AIMS: Multifocal hepatocellular carcinoma (HCC) is traditionally classified as multicentric occurrence (MO) or intrahepatic metastasis, a distinction that is difficult to apply in routine practice and not reflected in cu...AIMS: Multifocal hepatocellular carcinoma (HCC) is traditionally classified as multicentric occurrence (MO) or intrahepatic metastasis, a distinction that is difficult to apply in routine practice and not reflected in current staging systems. We aimed to assess the prognostic significance of different multifocal HCC patterns using simple, clinically applicable criteria. METHODS: We retrospectively analysed 153 patients with synchronous multifocal HCC who underwent surgical resection, including cases with two discrete nodules, more than two nodules and satellite nodules. 76 patients with solitary HCC served as controls. Histological classification based on Liver Cancer Study Group of Japan criteria was supplemented with promoter mutation analysis in selected cases. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: Histologic criteria alone failed to classify a substantial proportion of two-nodule HCCs. Although promoter analysis allowed partial reclassification, patients with undetermined two-nodule HCC had survival outcomes comparable to those classified as MO. In contrast, HCCs with satellite nodules showed significantly poorer OS and RFS. Multivariate analysis identified microvascular invasion and the presence of satellite nodules-but not two-nodule multifocality-as independent adverse prognostic factors. Notably, patients with two discrete nodules without satellite lesions did not show a statistically significant difference in OS or RFS compared with those with solitary HCC. CONCLUSIONS: Synchronous two-nodule HCC without satellite nodules represents a prognostically favourable subgroup distinct from satellite-nodule HCC. A simplified morphology-based stratification may better reflect clinical outcomes in multifocal HCC.
The classification and clinical implications of colorectal intramucosal adenocarcinoma remain controversial. Given the increasing frequency of diagnosis through colorectal cancer screening programmes, a reassessment of t...The classification and clinical implications of colorectal intramucosal adenocarcinoma remain controversial. Given the increasing frequency of diagnosis through colorectal cancer screening programmes, a reassessment of terminology and its impacts is necessary. This paper critically examines the diagnostic criteria, biological behaviour and clinical consequences of labelling these lesions as colorectal intramucosal carcinoma. While intramucosal adenocarcinoma exhibits cytological and architectural atypia beyond high-grade dysplasia, it remains confined to the mucosa and has minimal metastatic potential, with rare documented exceptions. Conversely, the use of carcinoma terminology has been associated with potential overtreatment, including unnecessary surgical resection, increased patient anxiety and financial burdens such as insurance complications. We explore geographic variations in classification and analyse the impact of terminology shifts. We propose a standardised framework that restricts the term intramucosal adenocarcinoma to intramucosal lesions exhibiting tumour budding or poorly differentiated clusters, signet ring cells, desmoplasia, vascular invasion, mucinous differentiation or features of neuroendocrine carcinoma, while reclassifying adenomas with cribriform architecture and complex glands as high-grade dysplasia. This nomenclature shift aims to reduce overtreatment, align with current oncologic understanding and ensure optimal patient care and communication.
AIMS: Malignant transformation of fibrous dysplasia (FD) in long bones is very rare. This study aimed to explore its clinicopathological and molecular characteristics to reveal the diagnostic features and pathogenesis. M...AIMS: Malignant transformation of fibrous dysplasia (FD) in long bones is very rare. This study aimed to explore its clinicopathological and molecular characteristics to reveal the diagnostic features and pathogenesis. METHODS: We conducted a clinicopathological analysis of 19 FD-associated sarcomas. Sanger and next-generation sequencing were used to detect molecular alterations, and clinical, radiological and histopathological features were reviewed in detail. RESULTS: The cohort consisted of 10 female and nine male patients (mean age, 48.4 years). Eleven patients had a previous diagnosis of FD, and eight patients presented de novo with acute symptoms like pain, swelling or dysfunction. Radiologically, in the monostotic cases (n=13), osteolytic lesions were observed with ill-defined margins, cortical destruction and soft tissue masses. Polyostotic cases (n=6) had both malignant masses and classic FD features of other skeletal sites. Histopathologically, osteosarcoma was the most common (57.9%), followed by undifferentiated pleomorphic sarcoma (26.3%), grade 2 spindle cell sarcoma (not otherwise specified, 5.3%) and low-grade central osteosarcoma (10.5%). Molecular analysis revealed identical mutations in paired FD and malignant components. Next-generation sequencing identified universal alterations (100%), along with concurrent (28.6%), (28.6%) and (28.6%) mutations, indicating a potential collaborative role in the FD malignant transformation process. CONCLUSIONS: Our analysis revealed unique clinicopathological characteristics and genetic markers in FD-associated sarcomas, deepening our knowledge of the mechanisms behind malignant transformation in FD and offering diagnostic tools for enhanced pathological assessment.
AIMS: The objective of this study was to explore the clinical diagnostic indicators and treatment approaches for intravenous leiomyomatosis (IVL), particularly when it extends into the inferior vena cava and the right he...AIMS: The objective of this study was to explore the clinical diagnostic indicators and treatment approaches for intravenous leiomyomatosis (IVL), particularly when it extends into the inferior vena cava and the right heart system. METHODS: Nine patients with IVL admitted to our hospital were enrolled in this study. The ultrasonographic, CT, MRI, pathological findings and surgical details of these patients were comprehensively analysed. All patients underwent surgical procedures. Postoperative pathological examination confirmed the presence of IVL, along with intramural leiomyoma of the uterus. RESULTS: Immunohistochemical results demonstrated that smooth muscle actin, smooth muscle myosin heavy chain, Desmin, Caldesmon, oestrogen receptor and progesterone receptor were highly positive. The Ki-67 index of most specimens was <3%, except for case 4. In case 4, which invaded the right atrium, the Ki-67 index ranged from 2% to 5%. Through molecular testing, this case with extension to the right atrium and inferior vena cava was identified as intraventricular smooth muscle neoplasia with fumarate hydratase deficiency. No copy number variation mutations were detected in all cases. CONCLUSIONS: Although IVL is a rare histologically benign tumour, it exhibits the capacity to infiltrate cardiac chambers and pulmonary vasculature. Therefore, early diagnosis via imaging techniques, precise assessment of the extent of intravenous leiomyoma involvement, complete lesion resection and perioperative administration of anti-oestrogen medications are pivotal for enhancing patient prognosis. Additionally, for cases with atypical nuclei or high Ki-67 levels, multidisciplinary collaboration is required to personalised treatment.
BACKGROUND: SMARCA4-deficient neoplasms are aggressive tumours typically arising in the thoracic region, often responding to immunotherapy despite poor prognosis. Although rare, these tumours can also occur in the gastro...BACKGROUND: SMARCA4-deficient neoplasms are aggressive tumours typically arising in the thoracic region, often responding to immunotherapy despite poor prognosis. Although rare, these tumours can also occur in the gastrointestinal tract, including the oesophagus. Given the potential for misdiagnosis, particularly when tumours present with undifferentiated morphology, this study aimed to identify key diagnostic features of SMARCA4-deficient undifferentiated carcinoma of the oesophagus (SMARCA4-deficient UC) and highlight the clinical importance of accurate diagnosis. MATERIAL AND METHOD: A retrospective review of 36 oesophageal carcinoma cases with undifferentiated histology was conducted following institutional review board approval. All cases underwent BRG1 (SMARCA4) immunohistochemical (IHC) staining, with complete loss of nuclear BRG1 expression used to identify SMARCA4-deficiency. Histopathologic evaluation and relevant clinical data were analysed. RESULTS: SMARCA4 deficiency was identified in 22 of 36 cases (61%). There were no significant differences in tumour morphology, size, association with Barrett's, or clinical presentation between SMARCA4-deficient and SMARCA4-intact cases. However, significant differences in immunophenotype were observed, particularly regarding keratin and synaptophysin expression. Notably, eight SMARCA4-deficient cases were initially misclassified as neuroendocrine carcinoma due to synaptophysin positivity. Despite low tumour mutation burden, patients with SMARCA4-deficient UC showed improved survival when treated with immunotherapy. Additionally, three SMARCA4-deficient tumours exhibited areas of differentiated carcinoma adjacent to undifferentiated components. CONCLUSIONS: Frequent synaptophysin expression in SMARCA4-deficient UC of the oesophagus can lead to diagnostic confusion with neuroendocrine carcinomas, resulting in potential mismanagement. BRG1 IHC should be incorporated in the diagnostic workup of poorly differentiated oesophageal tumours to ensure accurate classification and guide effective treatment strategies.
AIM: The clinical significance of histologic margin involvement by basal cell carcinoma (BCC)-associated stroma remains uncertain. This study aimed to determine the incidence of residual BCC in immediate re-excision spec...AIM: The clinical significance of histologic margin involvement by basal cell carcinoma (BCC)-associated stroma remains uncertain. This study aimed to determine the incidence of residual BCC in immediate re-excision specimens or clinical recurrence in cases managed without re-excision. METHODS: Fifty-eight cases of BCC with stromal margin involvement diagnosed between 2016 and 2020 were retrospectively reviewed. Fifty cases underwent immediate surgical re-excision, and eight were managed with clinical observation for at least two years. Tumors were classified by histologic subtype, and stromal margin involvement was categorized as peripheral, deep, or both. Residual carcinoma on re-excision or clinical recurrence within two years was recorded. RESULTS: Residual carcinoma was identified in 8% of re-excised cases (4/50) and occurred exclusively in tumors with a superficial component, including three pure superficial BCCs and one mixed superficial-nodular BCC; all residual tumors were of superficial subtype. No residual carcinoma was observed among 23 nodular or infiltrative BCCs that underwent re-excision. None of the eight cases managed with observation (1 superficial, 2 mixed superficial-nodular, 5 nodular) demonstrated clinical recurrence within two years. Overall, residual or recurrent disease occurred in 7% of cases (4/58). The distribution of adverse outcomes differed significantly by histologic subtype. CONCLUSIONS: Stromal margin involvement in non-superficial BCCs is rarely associated with residual or recurrent carcinoma. Adverse outcomes were confined to tumors containing a superficial component, highlighting biologic heterogeneity among BCC subtypes. These findings suggest that routine re-excision may be unnecessary for stromal-margin-positive BCCs lacking a superficial component and support more selective, subtype-informed management.
AIMS: Histological features of conventional malignant peripheral nerve sheath tumour (C-MPNST) resemble those of neurotrophic tropomyosin or tyrosine receptor kinase gene ()-rearranged spindle cell neoplasm, a new entity...AIMS: Histological features of conventional malignant peripheral nerve sheath tumour (C-MPNST) resemble those of neurotrophic tropomyosin or tyrosine receptor kinase gene ()-rearranged spindle cell neoplasm, a new entity of soft-tissue tumour. Pan-TRK immunohistochemistry has recently become popular for detecting rearrangements cost-effectively, but its positivity can also reflect neural differentiation. We investigated what pan-TRK positivity truly indicates in a large case series of neurogenic tumours. METHODS: Pan-TRK, S100, SOX10 and histone 3 lysine 27 trimethylation (H3K27me3) immunohistochemical analyses were performed on 99 C-MPNSTs, 17 malignant triton tumours, 8 epithelioid MPNSTs (E-MPNSTs), 2 atypical neurofibromatous neoplasms with uncertain biologic potential (ANNUBPs) and 1 glandular MPNST. For pan-TRK-positive cases, rearrangements were examined by molecular methods. RESULTS: 15 cases (11 C-MPNSTs, 3 E-MPNSTs and 1 ANNUBP) were positive for pan-TRK. Clinically, the positivity rates were significantly higher in older patients (≥50 years, 21.3% vs <50 years, 3.0%; p=0.0014) and sporadic cases (17.6% vs 5.1%; p=0.0287). In histological analyses, the positivity rate was significantly higher in E-MPNSTs than in C-MPNSTs (37.5% vs 11.1%; p=0.0333). Immunohistochemically, the expression of both S100 and SOX10 was significantly correlated with pan-TRK positivity (p=0.0310 and 0.0145, respectively). Although DNA-based sequencing was successfully performed for 11 cases, no evident rearrangements were detected. CONCLUSIONS: This study suggests that pan-TRK immunostaining may be useful for confirming neural differentiation in MPNST. However, whether its positivity reflects rearrangements or neural differentiation must be carefully assessed in combination with various immunohistochemical and molecular tests.
AIMS: Colorectal cancer (CRC) is increasingly detected at an early stage through national screening programmes, including tumours confined to the submucosa (pT1). Many pT1 CRC are managed by local endoscopic excision, an...AIMS: Colorectal cancer (CRC) is increasingly detected at an early stage through national screening programmes, including tumours confined to the submucosa (pT1). Many pT1 CRC are managed by local endoscopic excision, and histological risk assessment is central to determining the need for further treatment. METHODS: Clinical and pathology data were analysed for screen-detected pT1 CRC removed by local excision within the English Bowel Cancer Screening Programme (BCSP) between 2021 and 2022. The completeness of data recorded in the Bowel Cancer Screening System (BCSS) was audited against national pathology guidance. Clinicopathological features and subsequent management were described. RESULTS: 1267 pT1 CRC from 1260 patients were identified. BCSS data were available for all cases, although some histological fields were incomplete or coded as 'not assessable'. Most tumours were adenocarcinoma, not otherwise specified (NOS) (95.7%) and well-moderately differentiated (90.4%). Venous, lymphatic and perineural invasion were recorded in 8.9%, 9.2% and 1.0% of cases, respectively. Complete local resection (R0) was documented in 643 tumours. Following local excision, 342 pT1 CRC (27.0%) received further treatment, most commonly colorectal resection (287 cases) or repeat local excision (23 cases). Lymph node metastases were reported histologically in 33 patients. CONCLUSIONS: This large, contemporary cohort demonstrates that the English BCSP holds rich clinical and histological data suitable for audit and research. The audit highlights parameters where assessment is constrained by specimen-related factors and where data entry could be improved. These data characterise the histological features of locally excised pT1 CRC and their subsequent management and provide a foundation for future outcome-focused studies.
AIMS: The diagnosis and therapeutic decision-making in chronic myeloid leukaemia (CML) depend on the detection and quantification of . Currently, no clinical assay is used in routine practice to simultaneously quantify m...AIMS: The diagnosis and therapeutic decision-making in chronic myeloid leukaemia (CML) depend on the detection and quantification of . Currently, no clinical assay is used in routine practice to simultaneously quantify multiple isoforms, requiring separate tests for each isoform. To address this challenge, we have developed and optimised an assay (BloodHound) that leverages quantitative reverse transcription PCR (RT-qPCR) and high-resolution melting (HRM) technologies to simultaneously detect and quantify four isoforms (p190, p210, p230 and p203), with a limit of detection of 0.001%. METHODS: To evaluate the clinical utility of this assay, we analysed 895 peripheral blood and bone marrow samples from patients with suspected, established or relapsed CML. Sanger sequencing was used as an orthogonal method to confirm fusion junction identity, and the Qiagen ipsogen RT-qPCR assay was used for quantitative comparison. RESULTS: was detected in 20.9% of samples, with p210 alone being the most prevalent (86.1% (161/187), 95 CI 80.3% to 90.7%), followed by coexpression of p190 and p210 (12.3% (23/187), 95% CI 7.6% to 17.0%), while p190 alone (1.1% (2/187), 95% CI 0.1% to 3.8%) and p230 alone (0.5% (1/187), 95% CI 0% to 2.9%) were rare and p203 was not detected. The assay demonstrated high sensitivity and specificity, with 100% concordance with Sanger sequencing and showed excellent agreement with the Qiagen RT-qPCR assay (r=0.998). CONCLUSIONS: The present multiplex RT-qPCR/HRM assay may help streamline clinical workflows, enhance diagnostic precision and offer a practical platform for studying CML clonal dynamics. It also holds promise for facilitating interlaboratory standardisation of non-p210 quantification.
AIMS: Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast condition of unknown aetiology. It is a diagnosis of exclusion with a wide differential diagnosis. To date, no diagnostic guidelines exi...AIMS: Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast condition of unknown aetiology. It is a diagnosis of exclusion with a wide differential diagnosis. To date, no diagnostic guidelines exist for IGM in the UK. This scoping review aims to evaluate histopathological and microbiological approaches for the diagnosis of IGM. METHODS: A scoping review was performed by conducting a search of MEDLINE, Embase and Cochrane databases from 2003 to 2023. Studies involving human participants with histopathologically confirmed IGM were included. Data on histopathological and microbiological investigations were extracted and analysed. RESULTS: Out of 3208 search results, 225 studies involving 13 062 participants were included. Histological assessment was performed in 72.5% of participants, predominantly via core or excision biopsy. Microbiological investigations were inconsistently applied; only 47% of studies reporting the use of microscopy and culture. Only 24.9% of studies tested for tuberculosis using methods beyond histochemical Ziehl-Neelsen staining, and just 14 studies including 5% of participants described performing mycobacterial culture, despite this being the gold standard for diagnosis. was identified in several studies using advanced molecular techniques, suggesting possible misclassification of cystic neutrophilic granulomatous mastitis as IGM. CONCLUSIONS: Substantial heterogeneity exists in the diagnostic workup for IGM, particularly in excluding infectious and systemic causes. Histopathology alone is insufficient for definitive diagnosis. A comprehensive, standardised diagnostic framework that incorporates clinical, microbiological and epidemiological factors is needed to improve diagnostic accuracy and ensure appropriate management, particularly in the context of possible immunosuppressive therapy.