Journal of Clinical Pathology最新文献

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. Corynebacterium kroppenstedtii 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.

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: Histological features of conventional malignant peripheral nerve sheath tumour (C-MPNST) resemble those of neurotrophic tropomyosin or tyrosine receptor kinase gene (NTRK)-rearranged spindle cell neoplasm, a new entity of soft-tissue tumour. Pan-TRK immunohistochemistry has recently become popular for detecting NTRK 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, NTRK 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 NTRK 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 NTRK rearrangements or neural differentiation must be carefully assessed in combination with various immunohistochemical and molecular tests.

Aims: Although acute myeloid leukaemia (AML), myelodysplasia-related (AML-MR), can be defined solely by molecular abnormalities, legacy studies did not analyse the KMT2A gene. The KMT2A-partial tandem duplication (KMT2A-PTD) is described in myelodysplastic neoplasms (MDS) as well as AML. We describe the clinical, morphological, immunophenotypic and molecular features of AML harbouring KMT2A-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 KMT2A-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 KMT2A-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 KMT2A-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 IDH2 (30% of which were R172), FLT3 (32% each), RUNX1 (29%), DNMT3A and U2AF1 (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 KMT2A-PTD with or without MR-associated abnormalities were similar.

Conclusions: AML harbouring KMT2A-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.

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 TET2 (25.0%). Patients with SIADs showed a trend toward lower frequencies of ASXL1 (p=0.078) and NRAS (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 ASXL1 and NRAS 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.

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 TP53 hotspot mutation only in carcinoma. A germline MSH2 mutation was detected in all samples, and somatic MSH2 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 MSH2 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 BRCA2-like/HRD-associated mutational features in addition to shared TP53 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.

Diagnosing and identifying the type of porphyria in a patient requires specialist analysis of porphyrins and/or precursors in blood, urine and faeces. Correct sample storage and handling prior to analysis is essential to minimise preanalytical error.We evaluated the impact of light exposure, time and temperature on erythrocyte and plasma porphyrins in samples from patients with erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT) stored as whole blood for up to 96 hours, and in addition, the effect of freeze-thaw on plasma porphyrins in EPP, PCT and hereditary coproporphyria patient samples.Plasma porphyrins in the EPP patient samples decreased on average by 19% after 6 hours despite light protection and fridge storage, 36% by 24 hours stored light protected at room temperature, 67% within 1 hour when light exposed and 33% after one freeze-thaw cycle. In contrast, plasma porphyrin in PCT samples demonstrated greater stability compared to the EPP samples when stored light protected or exposed at room temperature and during freeze-thaw. Erythrocyte porphyrins in EPP samples were stable for 96 hours under all three storage conditions examined.Erythrocyte protoporphyrin analysis should be undertaken as an additional first-line investigation alongside plasma porphyrin analysis whenever protoporphyria needs to be excluded, due to the significant instability of plasma protoporphyrin.