Journal of Clinical Pathology最新文献

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 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 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 (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: To assess the impact of adding clinical comments to reports of thyroid function testing in patients treated for hypothyroidism.

Methods: We compared thyroid function test results in primary care patients being treated for hypothyroidism from January 2016 to August 2023 at two NHS Trusts with similar demographics and using the same instruments, but with different interpretative comment policies. One laboratory, Buckinghamshire Health Trust (Bucks), adds interpretative comments, whereas the other, Oxford University Hospitals (Oxford), does not. We used two outcome measures: the percentage of patients with thyroid-stimulating hormone (TSH) within the reference interval on repeat testing and the timing of repeat TSH testing samples, according to the National Institute for Health and Care Excellence guidance (NG145).

Results: We identified 18 242 and 31 655 hypothyroid patients (9.0% and 7.7% of the population tested) in Bucks and Oxford, with a total of 121 961 and 247 639 tests over the evaluation period, respectively. The proportion of TSH results within the reference interval (83.4% in Bucks, 83.9% in Oxford) was similar in both Trusts, as was TSH concentration (median TSH concentration 1.60 (IQR 0.78-2.82) mU/L in Bucks, 1.68 (IQR 0.97-2.76) in Oxford). The interval between tests was shorter in Oxford, but differed significantly from NG145 in both Trusts. Differences were statistically significant for both outcome measures, but of questionable clinical significance.

Conclusions: Adding interpretative comments to results of thyroid function tests does not appear to affect the distribution of TSH concentrations in primary care patients on thyroxine replacement or the intervals between tests in a clinically meaningful way.

Aims: Despite continually improving guidelines, human epidermal growth factor receptor 2 (HER2) testing for breast and gastro-oesophageal carcinoma continues to be a technical challenge in clinical laboratories. Manual HER2 fluorescence in situ hybridisation (FISH) testing is labour-intensive and prone to inter-run and interoperator variability. We aimed to adopt and validate a Leica BOND-III automated staining platform for HER2 FISH testing.

Methods: We recently validated the Leica BOND-III automated staining platform for HER2 FISH testing and compared it to our previous manual FISH (Agilent HER2 IQFISH pharmDx) methodology using 77 breast cancer cases and 8 gastric cancer cases.

Results: Using the automated Leica BOND-III automated staining platform, we achieved 0.95 sensitivity and 0.97 specificity in HER2 FISH testing for breast cancer cases and 1.0 sensitivity and specificity for gastric carcinoma cases. There was a 98% concordance rate between results of automated testing versus our previous manual method. The automated staining platform decreased technical hands-on time significantly while also reducing overall supply costs for the laboratory.

Conclusions: We were able to implement and validate the automated Leica BOND-III staining platform seamlessly into a complex laboratory for HER2 FISH testing that has overall significantly decreased hands-on time by technologists and supply costs. Automated Leica BOND-III HER2 FISH staining results were highly concordant with our previous manual FISH method in both breast cancer and gastric cancer cases.