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Study Type: Case series

Key Question: What are the clinicopathologic and molecular characteristics of low-grade appendiceal mucinous neoplasm (LAMN)-like lesions occurring outside the appendix?

Key Findings:

• Three cases of LAMN-like lesions in duplication cysts showed identical histologic features to appendiceal LAMN (low-grade mucinous epithelium, luminal mucin, mural fibrosis)
• All cases demonstrated intestinal immunophenotype (CK20+/CDX2+/CK7-) and harboured activating KRAS or GNAS mutations identical to conventional appendiceal LAMN
• Background duplication cyst features were present with confirmed absence of appendiceal involvement

Clinical Relevance: UK pathologists should recognise these rare extra-appendiceal LAMN-like lesions to ensure correct classification and appropriate clinical management, as they may require similar staging and surveillance protocols to appendiceal LAMN.

Limitations: Very small case series (n=3) limits generalisability of findings.

Study Type: Retrospective cohort study

Key Question: What is the frequency and pattern of melanocytic marker expression in uterine smooth muscle tumours, which could impact differential diagnosis with PEComas?

Key Findings:

• 38/102 (37.2%) uterine smooth muscle tumours expressed at least one melanocytic marker, most commonly PRAME (29.4%) and HMB-45 (15.6%)
• Expression was typically focal (<50% of cells in 90% of PRAME-positive cases) and weak intensity
• No tumour showed concurrent HMB-45 and Melan-A positivity, and no significant difference existed between benign and malignant tumours (36.8% vs 38.5%, p=0.88)

Clinical Relevance: UK pathologists should expect focal melanocytic marker expression in over one-third of uterine smooth muscle tumours, but dual HMB-45/Melan-A positivity or diffuse staining patterns should prompt reconsideration of PEComa diagnosis.

Limitations: Retrospective design with potential selection bias and lack of comparison with confirmed PEComa cases.

Study Type: Systematic review

Key Question: What are the current updates, controversies, and best practices in WHO/ISUP grading for clear cell and papillary renal cell carcinomas?

Key Findings:

• Key issues identified include grade heterogeneity, observer agreement challenges, and accuracy of needle biopsy grading compared to nephrectomy specimens
• Novel approaches emerging include incorporating necrosis into grading systems and pattern-based architectural grading methods
• Specific controversies highlighted around distinguishing grades 1 vs 2, quantifying sarcomatoid change percentage, and grading small papillary tumours ≤1.5cm

Clinical Relevance: Provides UK pathologists with evidence-based guidance on WHO/ISUP renal grading challenges commonly encountered in routine practice, particularly relevant given increasing use of nephron-sparing surgery and pre-operative biopsies.

Limitations: As a narrative review rather than systematic meta-analysis, recommendations may reflect author perspectives rather than standardised evidence synthesis.

Study Type: Retrospective cohort study

Key Question: What are the molecular characteristics and predictive biomarker profiles of gallbladder adenosquamous carcinoma (GBASC) in Caucasian patients?

Key Findings:

• 96% of GBASCs showed PD-L1 positivity (CPS >1), contrasting with absence of HER2 overexpression and universal mismatch repair proficiency
• PI3K pathway alterations were enriched in GBASCs: PIK3CA mutations in 44% and PTEN mutations in 24% of cases
• TP53 mutations occurred in 64% of cases, with CLDN18.2 expression limited to 28% and confined to glandular components

Clinical Relevance: These findings suggest GBASC represents a molecularly distinct entity from conventional gallbladder adenocarcinoma, potentially warranting different therapeutic approaches including PD-L1 and PI3K pathway-targeted therapies in UK practice.

Limitations: Small sample size of 25 cases limits generalisability of molecular frequency data.

Study Type: Case report

Key Question: Can low-risk HPV types 6/11 cause invasive carcinoma with mixed squamous and glandular features?

Key Findings:

• A 70-year-old woman developed invasive anal carcinoma with both squamous and mucinous glandular components arising within a Buschke-Löwenstein tumour
• In situ hybridisation confirmed LR-HPV types 6/11 in both benign condylomatous areas and invasive carcinoma components, with negative high-risk HPV testing
• Glandular component showed CK7-positive, CDX2/CK20-negative immunophenotype, excluding colorectal origin

Clinical Relevance: This challenges the traditional view that LR-HPV only causes benign lesions and documents the first reported case of LR-HPV-associated carcinoma with glandular differentiation, relevant for HPV testing interpretation and tumour classification in anal pathology.

Limitations: Single case report prevents assessment of frequency or clinical behaviour of this rare phenomenon.

Study Type: Retrospective case series

Key Question: What are the clinicopathological characteristics of unusual EMA-positive spindle cell tumours arising in the skull that resemble perineuriomas?

Key Findings:

• Eight cases identified in older adults (51-81 years, 75% female) presenting as lytic calvarial lesions with progressive growth on serial imaging
• Histologically uniform bland spindle cells positive for EMA (8/8) and Collagen IV (3/3), with limited SSTR2a expression, but negative for typical meningeal/neural markers (PR, S100, CD34, SOX10)
• No recurrence documented after curettage/excision over median 15.5 months follow-up (range 6-61 months)

Clinical Relevance: UK pathologists should recognise this distinct entity when evaluating calvarial spindle cell lesions, as accurate classification influences surgical management and patient counselling regarding prognosis.

Limitations: Small case series with relatively short follow-up period limiting long-term outcome assessment.

Study Type: Case series

Key Question: Can intramuscular myxoma exhibit chondroid differentiation, and what are the diagnostic implications?

Key Findings:

• Two cases of intramuscular myxoma showed previously unreported chondroid/chondromyxoid matrix with cartilaginous differentiation including chondrocytes in lacunar spaces
• One case harboured the characteristic GNAS c.602G>A (p.R201H) mutation; the other showed no pathogenic alterations on targeted sequencing
• Both tumours were deep intramuscular, T2 hyperintense on MRI with peripheral/septal enhancement, and showed typical myxoma immunoprofile (variable CD34, negative S100)

Clinical Relevance: UK pathologists should recognise this morphological variant to prevent misdiagnosis as chondrosarcoma, chondromyxoid fibroma, or other chondromyxoid neoplasms, ensuring appropriate conservative management.

Limitations: Very small case series limits generalisability of findings.

Study Type: Retrospective case series

Key Question: What is the spectrum of gynecologic tumors and precursor lesions in women with Li-Fraumeni syndrome caused by germline TP53 mutations?

Key Findings:

• Seven gynecologic cancers identified (high-grade serous carcinomas n=3, endometrial serous carcinoma n=1, leiomyosarcomas n=2, high-grade endometrioid ovarian carcinoma n=1) with somatic TP53 inactivation in 6/7 cases
• Novel p53-aberrant endometrial glandular lesions resembling atypical hyperplasia occurred in young women (median age 33) and responded to progestin therapy or resolved after hysterectomy
• Aberrant p53 expression patterns in morphologically benign tissues may indicate underlying germline TP53 mutations

Clinical Relevance: UK pathologists should recognise that aberrant p53 staining in young women's gynecologic specimens, particularly endometrial lesions resembling atypical hyperplasia, may indicate Li-Fraumeni syndrome requiring genetic counselling.

Limitations: Small sample size (20 patients) limits generalisability of findings.