Austin John McHenry

All Publications

• Prospective Fumarate Hydratase Tumor Predisposition Syndrome Screening in Patients With Uterine Smooth Muscle Tumors: Age, Morphology, Fumarate Hydratase/S-(2-succino) Cysteine Immunohistochemistry, and Germline Testing. The American journal of surgical pathology McHenry, A., Monsrud, A., Pors, J., Folkins, A., Longacre, T., Hodan, R. 2025

  Abstract

  Fumarate hydratase tumor predisposition syndrome (FHTPS) is caused by germline fumarate hydratase (FH) pathogenic variants (PVs). Most women with FHTPS develop FH-deficient (FHD) uterine leiomyomas (ULs), which arise 10 to 15 years earlier than aggressive FHD-renal cell carcinoma. We evaluate a previously proposed FHTPS screening strategy for women with ULs. This 5-year, prospective and retrospective study performed FH and later S-(2-succino) cysteine immunohistochemistry (IHC) on all uterine smooth muscle (USM) tumors in patients 40 (later ≤30) years or younger and on all USM tumors with suggestive FHD morphology regardless of age. Patients with FHD tumors by IHC were referred to genetic counseling. Of 840 USM tumors, 112 FHD-tumors by IHC (13%) were identified, all with suggestive FHD-morphology; 44 patients (39%) underwent germline testing, and 15 harbored germline FH PVs (34.1% of germline tested, 13.4% of all FHD-tumors). While FHD tumors were seen across a wide age range (24 to 73 y), those with germline FH PVs were significantly younger (median 33 vs 44 years wild-type, P = 0.0032). Few (12.5%) patients ≥40 and no patients ≥50 had a germline FH PV, whereas a majority (60%) of patients <40 (86% of those <30) had a germline FH PV. We demonstrate that previously proposed resource-conscious screening involving morphology and IHC is effective for identifying women with FHTPS. We provide prospective data confirming patients presenting with FHD-ULs over age 50 are unlikely to harbor germline FH PVs and argue that for germline testing without consideration of other factors, a threshold of younger than 50 years may be appropriate.

  View details for DOI 10.1097/PAS.0000000000002362

  View details for PubMedID 39835370

• Airway associated inflammation in post-transplant cystic fibrosis patients as a predictor of chronic lung allograft dysfunction (CLAD). Journal of clinical pathology Patel, T., Bemiss, B., Panah, E., Chaiprasit, T., McHenry, A., Venkataraman, G., Ananthanarayanan, V. 2025

  Abstract

  In cystic fibrosis lung transplant recipients (LTRs), graft dysfunction due to acute infections, rejection or chronic lung allograft dysfunction (CLAD) is difficult to distinguish. Characterisation of the airway inflammatory milieu could help detect and prevent graft dysfunction. We speculated that an eosinophil or neutrophil-rich milieu is associated with higher risk of CLAD.A retrospective, single-centre observational study of cystic fibrosis LTRs between 2002 and 2021 was performed. Data from biopsy slides, pulmonary function testing and bronchoalveolar lavage fluid microbiology tests were collected. The primary outcome was bronchiolitis obliterans syndrome (BOS) or death after transplant, with an 8-year follow-up period.40 patients were identified with an average age of 35.3 at first transplantation, including 5 redo lung transplants. Fungal infections were correlated with higher rejection scores (p<0.01) and survival status (p=0.027). Fungal and bacterial infection rates were reduced in later transplants (2014-2021) compared with earlier (2002-2014). Fungal infections were associated with significantly worsened outcomes (p≤0.001). Eosinophils in large airways was associated with worse BOS-free survival (p=0.03).Subcategorisation of the inflammatory milieu (particularly noting eosinophils) in surveillance biopsies may help detect CLAD earlier and improve long-term outcomes in cystic fibrosis LTRs.

  View details for DOI 10.1136/jcp-2024-209899

  View details for PubMedID 39779317

• Molecular classification of metastatic and recurrent endometrial endometrioid carcinoma: prognostic relevance among low- and high-stage tumours. Histopathology McHenry, A., Devereaux, K., Ryan, E., Chow, S., Allard, G., Ho, C. C., Suarez, C. J., Folkins, A., Yang, E., Longacre, T. A., Charu, V., Howitt, B. E. 2024

  Abstract

  AIMS: Molecular classification according to The Cancer Genome Atlas (TCGA) improves endometrial endometrioid carcinoma (EEC) prognostication and has specific treatment implications; however, original data were skewed towards low-grade and low-stage tumours. Herein, we molecularly classify EECs metastatic at the time of diagnosis or with subsequently documented recurrent/metastatic disease to examine correlation with clinical outcomes.METHODS: TCGA categories include POLE-mutated, microsatellite instability (MSI), p53 abnormal (p53 abnl) and no specific molecular profile (NSMP). POLE targeted sequencing at exons 9, 11, 13 and 14 and immunohistochemistry (IHC) for PMS2, MSH6 and p53 were performed to establish molecular classification.RESULTS: The distribution in our cohort of 141 EECs was similar to that generally reported in EEC, with nine POLE-mutated (6%), 45 MSI (32%), 16 p53 abnl (11%) and 71 NSMP (50%), with similar distributions between low- and high-stage cohorts. We demonstrate that when stratified by molecular subtype, disease-specific survival from the time of high-stage (stages III-IV) presentation or time of recurrence in low-stage (stages I-II) disease among metastatic and/or recurrent EEC is strongly associated with TCGA classification (high-stage P=0.02, low-stage P=0.017). Discordant molecular classification between primary and metastatic/recurrent tumours occurred in four of 105 (3.8%) patients, two related to PMS2/MSH6 IHC and two related to p53 IHC.CONCLUSIONS: We demonstrate that molecular classification is prognostically relevant not only at the time of diagnosis, but also at the time of recurrence and in the metastatic setting. Rare subclonal alterations occur and suggest a role for confirming TCGA classification in recurrent/metastatic tumours.

  View details for DOI 10.1111/his.15232

  View details for PubMedID 38859768

• Scattering-Based Light Sheet Microscopy Imaging of HPV-Associated Squamous Lesions of the Anal Canal: A Proof-of-Principle Study. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Liang, B., Zhao, J., Kim, Y., Barry-Holson, K. Q., Bingham, D. B., Charville, G. W., Darragh, T. M., Folkins, A. K., Howitt, B. E., Kong, C. S., Longacre, T. A., McHenry, A. J., Toland, A. M., Zhang, X., Lim, K., Khan, M. J., Kang, D., Yang, E. J. 2024: 100493

  Abstract

  Demand for anal cancer screening is expected to rise following the recent publication of the ANCHOR trial, which showed that treatment of HSIL significantly reduces the rate of progression to anal cancer. While screening for HPV-associated squamous lesions in the cervix is well-established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy (HRA) with biopsies. This procedure has a steep learning curve for providers and may cause patient discomfort. Scattering-based light-sheet microscopy (sLSM) is a novel imaging modality with the potential to mitigate these challenges through real-time, microscopic visualization of disease-susceptible tissue. Here, we report a proof-of-principle study that establishes feasibility of dysplasia detection using an sLSM device. We imaged 110 anal biopsy specimens collected prospectively at our institution's dysplasia clinic (including 30 nondysplastic, 40 LSIL and 40 HSIL specimens) and found that these optical images are highly interpretable and accurately recapitulate histopathologic features traditionally used for the diagnosis of HPV-associated squamous dysplasia. A reader study to assess diagnostic accuracy suggests that sLSM images are noninferior to H&E for the detection of anal dysplasia (sLSM accuracy = 0.87, H&E accuracy = 0.80; p = 0.066). Given these results, we believe that sLSM technology holds great potential to enhance the efficacy of anal cancer screening by allowing accurate sampling of diagnostic tissue at the time of anoscopy. While the current imaging study was performed on ex vivo biopsy specimens, we are currently developing a handheld device for in vivo imaging that will provide immediate microscopic guidance to HRA providers.

  View details for DOI 10.1016/j.modpat.2024.100493

  View details for PubMedID 38615709

• A comparison of S-(2-succino) Cysteine (2SC) and Fumarate Hydratase (FH) Immunohistochemistry for Screening of Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) Syndrome in Uterine Smooth Muscle Tumors Monsrud, A., McHenry, A., Pors, J., Folkins, A., Hodan, R., Longacre, T. ELSEVIER SCIENCE INC. 2024: S1213-S1214

  View details for Web of Science ID 001302363404098

• Paneth Cells in Ovarian Mucinous Tumors Are Indicative of a Primary Ovarian Neoplasm McHenry, A., Folkins, A., Longacre, T. ELSEVIER SCIENCE INC. 2024: S1208-S1210

  View details for Web of Science ID 001302363404094

• Age as a Surveillance Factor for Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) Syndrome Screening in Uterine Leiomyomas with Fumarate Hydratase (FH) And S(2-Succino) Cysteine (2SC) Immunohistochemistry McHenry, A., Monsrud, A., Pors, J., Hodan, R., Folkins, A., Longacre, T. ELSEVIER SCIENCE INC. 2024: S1207-S1208

  View details for Web of Science ID 001302363404093

• Human herpesvirus 8-negative effusion-based large B-cell lymphoma: a distinct entity with unique clinicopathologic characteristics. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Gisriel, S. D., Yuan, J., Braunberger, R. C., Maracaja, D. L., Chen, X., Wu, X., McCracken, J., Chen, M., Xie, Y., Brown, L. E., Li, P., Zhou, Y., Sethi, T., McHenry, A., Hauser, R. G., Paulson, N., Tang, H., Hsi, E. D., Wang, E., Zhang, Q., Young, K. H., Xu, M. L., Pan, Z. 2022

  Abstract

  Rare cases of human herpesvirus 8 (HHV8)-negative effusion-based large B-cell lymphoma (EB-LBCL) occur in body cavities without antecedent or concurrent solid mass formation. In contrast to HHV8+primary effusion lymphoma (PEL), EB-LBCL has no known association with HIV or HHV8 infection. However, the small sample sizes of case reports and series worldwide, especially from non-Japanese regions, have precluded diagnostic uniformity. Therefore, we conducted a retrospective, multi-institutional study of 55 cases of EB-LBCL and performed a comprehensive review of an additional 147 cases from the literature to identify distinct clinicopathologic characteristics. In our study, EB-LBCL primarily affected elderly (median age 80 years), immunocompetent patients and manifested as lymphomatous effusion without a solid component. The lymphomatous effusions mostly occurred in the pleural cavity (40/55, 73%), followed by the pericardial cavity (17/55, 31%). EB-LBCL expressed CD20 (53/54, 98%) and PAX5 (23/23, 100%). Most cases (30/36, 83%) were of non-germinal center B-cell subtype per the Hans algorithm. HHV8 infection was absent (0/55, 0%), while Epstein-Barr virus was detected in 6% (3/47). Clinically, some patients were managed with drainage alone (15/34, 44%), while others received rituximab alone (4/34, 12%) or chemotherapy (15/34, 44%). Eventually, 56% (22/39) died with a median overall survival (OS) of 14.9 months. Our findings were similar to those from the literature; however, compared to the non-Japanese cases, the Japanese cases had a significantly higher incidence of pericardial involvement, a higher rate of chemotherapy administration, and longer median OS. Particularly, we have found that Japanese residence, presence of pericardial effusion, and absence of MYC rearrangement are all favorable prognostic factors. Our data suggest that EB-LBCL portends a worse prognosis than previously reported, although select patients may be managed conservatively. Overall, EB-LBCL has distinct clinicopathologic characteristics, necessitating the establishment of separate diagnostic criteria and consensus nomenclature.

  View details for DOI 10.1038/s41379-022-01091-x

  View details for PubMedID 35562413