Looking beyond workforce parity: addressing gender inequity in pathology.

While women pathologists have made up over one-third of pathologists in the Australian workforce for over 15 years and at least 50% since 2019, they are under-represented in senior leadership roles, scientific publications, grant recipients, editorial boards, key presentations, and professional awards. This is not unique to pathology and is seen in the broader medical and academic community. Barriers to gender equity and equality in pathology, medicine and academia include gender stereotypes, gender-based discrimination, structural and organisational barriers as well as broader social and cultural barriers. A diverse leadership reflective of the whole professional body and the broader community is important for optimal health outcomes. It is the responsibility and moral duty of individuals and organisations to address any gender disparities, inequities, and inequalities by monitoring, identifying, and acting on gender biases and systemic barriers that hinder appropriate levels of representation by women.

Large cell calcifying Sertoli cell tumour: molecular and immunohistochemical assessment of a series comprising non-metastasising and metastasising neoplasms.

Large cell calcifying Sertoli cell tumour (LCCSCT) is a type of testicular sex cord-stromal tumour that may occur sporadically or in the context of Carney complex and other genetic syndromes. A subset is clinically malignant, and the molecular mechanisms that drive such aggressive behaviour remain unknown. METHODS AND RESULTS: We analysed 21 samples from 20 patients with LCCSCT (12 non-metastasising and eight metastasising) using PRKAR1A immunohistochemistry (IHC) and next-generation sequencing. All tumours except two (cases 17 and 20, both metastasising) demonstrated loss of PRKAR1A expression. Among 11 cases with interpretable sequencing results, all harboured pathogenic single nucleotide variants of PRKAR1A. Evidence of loss of heterozygosity (LOH) of PRKAR1A was present in all tumours with interpretable zygosity data, but the mechanisms of LOH were different for non-metastasising and metastasising tumours. Non-metastasising tumours demonstrated only copy-neutral LOH, while metastasising tumours demonstrated a spectrum of mechanisms of LOH, including copy-loss LOH, two concurrent mutations or copy-neutral LOH. Relevant molecular findings in non-metastasising LCCSCT were limited to PRKAR1A variants. In contrast, all metastasising LCCSCTs with interpretable data harboured additional pathogenic variants, including (but not restricted to) BRCA2 mutations with evidence of LOH and bi-allelic CDKN2A/B deletions. Three patients harboured PRKAR1A variants of inferred germline origin, including one with Carney complex and two without known syndromic features. CONCLUSIONS: This study further confirms that PRKAR1A IHC is a useful diagnostic tool for both non-metastasising and metastasising tumours and suggests that molecular analyses can be helpful to identify non-metastasising tumours with malignant potential in selected patients. Importantly, these results highlight that germline assessment could be beneficial for all patients presenting with LCCSCT.

Myoid gonadal stromal tumours are characterised by recurrent chromosome-level copy number gains: molecular assessment of a multi-institutional series.

Myoid gonadal stromal tumours (MGST) represent a rare type of testicular sex cord-stromal tumour that has recently been recognised as a distinct entity by the World Health Organization (WHO) classification of genitourinary tumours. MGSTs affect adult men and have been reported to behave in an indolent fashion. Histologically, MGSTs are pure spindle cell neoplasms that coexpress SMA and S100 protein. Given that the molecular features of these neoplasms remain largely undescribed, we evaluated a multi-institutional series of MGSTs using DNA and RNA sequencing. This study included 12 tumours from 12 patients aged 28 to 57 years. Tumour sizes ranged from 0.6 to 4.3 cm. Aggressive histologic features, such as vascular invasion, necrosis, invasive growth, and atypical mitoses were invariably absent. Mitotic activity was low, with a median of less than 1 mitosis per 10 high power fields (HPF; maximum: 3 mitoses per 10 HPF). Molecular analyses did not identify recurrent mutations or gene fusions. All cases with interpretable copy number variant data (9/10 cases sequenced successfully) demonstrated a consistent pattern of chromosome arm-level and whole-chromosome-level copy number gains indicative of ploidy shifts, with recurrent gains involving chromosomes 3, 6, 7, 8, 9, 11, 12, 14q, 15q, 17, 18q, 20, and 21q. Similar findings have also been recognised in pure spindle cell and spindle-cell predominant sex cord-stromal tumours without S100 protein expression. MGSTs are characterised by ploidy shifts and may be part of a larger spectrum of spindle cell-predominant sex cord-stromal tumours, including cases without S100 protein expression.

Inflammatory lobular hemangioma (T-cell-rich angiomatoid polypoid pseudolymphoma)-Assessment of FOS/FOSB and lymphoid markers and comparison with epithelioid hemangioma.

BACKGROUND: T-cell-rich angiomatoid polypoid pseudolymphoma (TRAPP) and inflammatory lobular hemangioma (ILH) encompass a spectrum of cutaneous vascular lesions in which a prominent lymphoplasmacytic component may impart a pattern highly reminiscent of low-grade cutaneous lymphoma (pseudolymphoma). Epithelioid hemangioma, including its most common variant angiolymphoid hyperplasia with eosinophilia (ALHE), is a distinct entity associated with FOS and/or FOSB expression detected by immunohistochemistry (IHC). These entities can show significant morphological overlap. METHODS: We performed IHC for FOSB, FOS, and lymphoid markers in a series of TRAPP/ILH and ALHE. RESULTS: We identified 13 cases of ILH/TRAPP, which showed a predominance in CD8+ T-cells (CD8>CD4: 11/13) while FOSB and FOS were expressed in 36% (4/11) and 27% (3/11) of cases, respectively. ALHE (n = 9) showed a predominance in CD4+ T-cell (67%) with FOSB and FOS co-expression in 78% (seven of nine) of the cases. CONCLUSION: We showed, based on FOS and/or FOSB immunohistochemical expression, that there is a possible link between ILH/TRAPP and epithelioid hemangioma/ALHE. The use of FOS and FOSB IHC in the routine diagnostic setting of cutaneous vascular lesions will help to redefine cases of ILH/TRAPP as a subset of these may represent inflammatory variants of epithelioid hemangioma.

Prostatic malakoplakia: clinicopathological assessment of a multi-institutional series of 49 patients.

Prostatic malakoplakia (MP) is rare, with only case reports and small series (< five patients) available in the literature. In this study we analysed an international multi-institutional series of 49 patients with prostatic MP to more clearly define its clinicopathological features. The median age was 67 years and the median serum prostate-specific antigen (PSA) was 7.5 ng/ml. MP was clinically manifest in most cases (28 of 45 patients with data available, 62%). Of 43 patients with detailed clinical history available, 21 (49%) had concurrent or metachronous malignancies (including prostate cancer). Diabetes or insulin resistance was present in 11 patients (26%). Additionally, three patients had a history of solid organ transplantation and one had HIV. Of note, six of 34 patients (18%) without concurrent prostate cancer had an abnormal digital rectal examination and/or lesions on magnetic resonance imaging (MRI) with prostate imaging reporting and data system (PIRADS) scores 4-5. The initial diagnosis was made on core biopsies (25 of 49, 51%), transurethal resection specimens (12 of 49, 24%), radical prostatectomies (10 of 49, 20%), Holmium-laser enucleation (one of 49, 2%) and cystoprostatectomy (one of 49, 2%). Tissue involvement was more commonly diffuse or multifocal (40 of 49, 82%). Von Kossa and periodic acid-Schiff stains were positive in 35 of 38 (92%) and 26 of 27 lesions (96%), respectively. Of note, two cases were received in consultation by the authors with a preliminary diagnosis of mesenchymal tumour/tumour of the specialised prostatic stroma. The present study suggests that prostatic MP is often associated with clinical findings that may mimic those of prostate cancer in a subset of patients. Moreover, MP may be found incidentally in patients with concurrent prostate cancer.

Greater Attendance at a Community Weight Loss Programme over the First 12 Weeks Predicts Weight Loss at 2 Years.

BACKGROUND: There is considerable heterogeneity in long-term weight loss among people referred to obesity treatment programmes. It is unclear whether attendance at face-to-face sessions in the early weeks of the programme is an independent predictor of long-term success. OBJECTIVE: To investigate whether frequency of attendance at a community weight loss programme over the first 12 weeks is associated with long-term weight change. METHODS: Participants were randomised to receive brief support only (control, n = 211), or a weight loss programme for 12 weeks (n = 530) or 52 weeks (n = 528). This study included participants with data on session attendance over the first 12 weeks (n = 889) compared to the control group. The association between attendance (continuously) and weight loss was explored using a linear model. A multi-level mixed-effects linear model was used to investigate whether attendance (categorised as 0, 1, 2-5, 6-9, and 10-12 sessions) was associated with weight loss at 3, 12, and 24 months compared to the control. RESULTS: For every session attended in the first 12 weeks, the average weight loss was -0.259 kg/session at 24 months (p = 0.005). Analysis by attendance group found only those attending 10-12 sessions had significantly greater weight loss (-7.5 kg [95% CI -8.1 to -6.9] at 12 months; -4.7 kg [95% CI -5.3 to -4.1] at 24 months) compared to the control group (-3.4 [95% CI -4.5 to -2.4] at 12 months, -2.5 [95% CI -3.5 to -1.5] at 24 months). Early attendance was higher for people ≥70 years, but there was no evidence of a difference by gender, ethnicity, education, or income. CONCLUSIONS: Greater attendance at a community weight loss programme in the first 12 weeks is associated with enhanced weight loss up to 24 months. Regular attendance at a programme could be used as a criterion for continued provision of weight loss services to maximise the cost-effectiveness of interventions.