Jessica Berger¹, Ricardo Vilain¹, Frank Alvaro^2
1Department of Anatomical Pathology, John Hunter Hospital, Newcastle, NSW, Australia
²Department of Paediatric Oncology, John Hunter Hospital, Newcastle, NSW, Australia

Introduction
Our case of anaplastic epithelioid pleomorphic xanthoastrocytoma (aePXA) is a rare variant of WHO Grade 3 PXA with a morphological and molecular mimic. Its doppelganger, the epithelioid variant of glioblastoma (eGBM) has been recently stratified to include the PXA-like eGBM subtype (1, 2).  In light of our case’s resemblance with PXA-like eGBM, we compared the features of aePXA and its pathological cousins to illustrate a diagnostic pitfall.

Case report
A 13 year old male with a 6cm brain tumour exhibited epithelioid morphology, microvascular proliferation and necrosis, bearing a striking similarity to eGBM. The final diagnosis was anaplastic epithelioid, WHO Grade 3 PXA. We reviewed the literature and provided tables with comparison of features between classical PXA, aePXA and PXA-like GBMs. 

Discussion
aePXA and PXA-like eGBM show significant overlap in clinical and pathological features. We conclude that aePXA and PXA-like eGBM are so closely related, that they are only distinguishable by the identification of a classical PXA precursor with eosinophilic granular bodies in the former. As in our case, such eosinophilic bodies can be focal, largely overrun by high grade transformation or in other instances, potentially unsampled (3). The relationship between eGBM and the malignant progression of PXA needs further clarification. Whether subtypes of these two tumours will be considered as the same or closely related entities in future WHO nomenclature remains to be elucidated. (219 words)

Statement of originality: This work is original and contributed by the authors.  

Cindy Y.L. Khu¹, Claudia Di Bella², John Slavin¹

¹Department of Anatomical Pathology, St. Vincent’s Hospital, Melbourne, Australia

²Department of Orthopaedic Surgery, St. Vincent’s Hospital, Melbourne, Australia

 

Phosphaturic mesenchymal tumour (PMT) is a rare bone or soft tissue neoplasm frequently associated with osteomalacia secondary to tumour production of fibroblast growth factor 23 (FGF23). Clinical manifestations include bone pain, hypophosphatemia and osteomalacia. We present a case series of 4 patients seen in our institution over 14 years. The median age of diagnosis is 49 years with a median time to diagnosis of 65 months. All cases involved the appendicular skeleton, with 3 benign cases and 1 with malignant recurrence and distant metastasis. On histology, benign PMT is composed of spindle to stellate cells with characteristic flocculent, smudgy-appearing calcified matrix with surrounding prominent vessels and osteoclast-type giant cells. Mitotic activity, necrosis and persistent hypophosphatemia after tumour resection were a feature of malignant PMT. Immunohistochemical stains CD56, FGF23, SATB2 and SSTRA2A are useful in differentiating PMT from morphological mimics.1 Majority of PMTs are benign in nature, with complete resection of the tumour resulting in resolution of symptoms. The diagnosis of PMT is challenging and often delayed owing to the unapparent, slow-growing nature of the tumour leading to difficulty localising the lesion, the rarity of this disease, and the histological overlap with other diseases. 

 

1. Agaimy, A., et al., Phosphaturic Mesenchymal Tumors: Clinicopathologic, Immunohistochemical and Molecular Analysis of 22 Cases Expanding their Morphologic and Immunophenotypic Spectrum. Am J Surg Pathol, 2017. 41(10): p. 1371-1380.

 

Author CYLK participated in reporting the case, conducted the literature review and compiled the abstract. 

Author CDB contributed to the content included in the abstract.

Author JLS reported the case and contributed to the content included in the abstract.

Xinyi Qu¹, Noel Chia¹, Puay Hoon Tan^2,3, Wong Fuh Yong⁴, Phyu Nitar⁵, Mihir Gudi²

¹Department of Pathology, National University Hospital, Singapore 

²Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore 

³Luma Medical Centre, Royal Square Medical Centre, Singapore

⁴Division of Radiation Oncology, National Cancer Centre, Singapore 

⁵Department of Cancer Informatics, National Cancer Centre Singapore, Singapore 

 

Background: HER2-negative breast cancers comprise approximately 50% of breast cancers and include HER2-low, -ultra low and -null subcategories. These tumors showed good response to trastuzumab deruxtecan in the DESTINY-Breast04 trial and DESTINY-Breast06 data showed similar response in HER2-low and -ultra low groups. This study investigates the incidence of HER2-positive, -low, -ultra low and -null tumors and correlation with clinicopathologic parameters in Singapore.

 

Design: This retrospective cohort study included 7809 patients with invasive breast cancer and HER2 IHC and ISH results. The variables analyzed include 5-year overall survival, pCR, age, race, multifocality, histologic type, grade, stage, and hormone receptor, lymph node and metastasis status.

 

Results: 28.3% of the patients had HER2-low, 9.3% had HER2-ultra low, 35% had HER2-null and 27.3% had HER2-positive tumors. The HER2-negative groups more commonly showed special histologic type, lower grade and stage, positive hormone receptor, negative lymph nodes, lower metastasis rate and lower pCR rate. The overall survival was slightly higher for HER2-low and -ultra low tumors (p=0.001).

 

Conclusion: In Singapore, HER2-low and -ultra low tumors comprise 37.6% of breast cancers and have a more favorable 5-year overall survival than HER2-positive and -null tumors. Further investigation is needed to determine whether the HER2-negative subcategories are truly distinct.

 

Statement of contribution: The corresponding author contributed to the literature review, data interpretation and discussion sections of the paper.

Kai Zong Teo¹, Dale Wright^2,4, Ali Moghimi^1,3

¹Department of Histopathology, The Children’s Hospital at Westmead, Sydney, NSW, Australia 

²Department of Cytogenetics, The Children’s Hospital at Westmead, Sydney, NSW, Australia

³Faculty of Medicine and Health, The Children's Hospital at Westmead Clinical School, University of Sydney, Sydney, NSW, Australia.

⁴Specialty of Genomic Medicine, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

Introduction:  Small cell osteosarcoma (SCOS) is a rare variant of osteosarcoma that mimics other round cell tumours of bone, particularly Ewing sarcoma (ES).[1-2] NKX2.2 immunohistochemistry has greatly improved distinction between SCOS and ES.[3]  

Aims: We present a previously undescribed finding of SCOS with positive NKX2.2 immunohistochemical staining. 

Case description: A 14-year-old boy was investigated for an FDG-avid mass in the left humeral diaphysis showing cortical erosion and muscle involvement. Core biopsy showed uniform round to oval, and occasional larger pleomorphic tumour cells, with necrosis, scattered mitotic and apoptotic nuclei, laciform woven bone, and cartilage formation. The tumour showed strong nuclear staining for SATB2 and p53, and NKX2.2 nuclear staining in many cells. No gene rearrangement of EWSR or FUS was identified on FISH or RNA sequencing. Chromosome microarray revealed a highly complex copy-number profile with near doubling of tumour genomic material more typical of osteosarcoma.

Discussion: The positive NKX2.2 expression is likely an incidental upregulation of transcription factors secondary to the complex tumour mutation profile. It is of unknown clinical significance and did not alter patient management. However importantly, it demonstrates a novel finding which if unknown to the reporting pathologist may lead misdiagnosis in particularly limited biopsies resulting in suboptimal management of disease.

References
1. Baumhoer D, Rosenberg AE, Cates JMM, et al. Osteosarcoma [Internet]. World Health Organization. World Health Organization; 2020 [cited 2024 Aug 7]. Available from: https://tumourclassification.iarc.who.int/chaptercontent/33/153 
 2. Righi A, Gambarotti M, Longo S, et al. Small cell osteosarcoma: clinicopathologic, immunohistochemical, and molecular analysis of 36 cases. Am J Surg Pathol. 2015 May;39(5):691-9. doi: 10.1097/PAS.0000000000000412. PMID: 25723116.
 3. Hiemcke-Jiwa LS, Sumathi VP, Baumhoer D, et al. Small cell osteosarcoma versus fusion-driven round cell sarcomas of bone: retrospective clinical, radiological, pathological, and (epi)genetic comparison with clinical implications. Virchows Arch. 2024 Mar;484(3):451-463. doi: 10.1007/s00428-024-03747-2. Epub 2024 Feb 9. PMID: 38332052; PMCID: PMC11021258.
  

This abstract is my (Kai Zong Teo) own original work with corrections and suggestions from Ali Moghimi and Dale Wright.

Anthony Jeffrey^1,2, Michelle Choy³, Nisha Singh⁴, Kit Double⁵, Poomahal Kumar^1,2,3

¹Department of Haematology, NSW Health Pathology, Royal North Shore Hospital, St, Leonards, Australia

²Department of Medicine, The University of Sydney, Sydney, Australia

³Department of Flow Cytometry, NSW Health Pathology, Royal North Shore Hospital, St, Leonards, Australia 

⁴Department of Cytogenetics, NSW Health Pathology, Royal North Shore Hospital, St, Leonards, Australia 

⁵Department of Psychology, The University of Sydney, Sydney, Australia 

Background: Flow cytometry immunophenotyping (FCI) and cytogenetic analysis are diagnostic and prognostic investigations performed on bone marrow biopsy specimens. When a particulate aspirate sample cannot be obtained, trephine samples can be disaggregated to yield cellular material for analysis. 

Methods: Retrospective data collection on the performance of mechanical trephine disaggregation for FCI and cytogenetics between 2019-2023 at Royal North Shore Hospital.

Results: Trephine disaggregation for FCI due to suboptimal aspirate material was required in 83 cases representing 1.3% of all bone marrow biopsies performed during the study period. The most common pathology leading to inadequate aspirate material was primary myelofibrosis in 15/83 cases (18%). Sufficient analytical information to publish a FCI diagnostic report was present in 56/83 cases (67%). FCI was successful in 100% of cases of acute leukaemia. Karyotyping was attempted on disaggregated trephine samples in 64 cases. 19/64 cases (30%) yielded metaphases to perform a karyotype. Cytogenetic abnormalities with diagnostic or prognostic significance were identified in 8/19 cases (42%).

Conclusion: Mechanical trephine disaggregation results in adequate cellular yields from suboptimal samples for successful FCI in most cases, with a faster turnaround time than immunohistochemistry. Success rates for karyotyping on disaggregated trephines are low, however, provide important information for patient management. 

Author contribution statement: AJ collected data, drafted the manuscript and contributed to study design and conception. MC and NS provided scientific guidance on result interpretation, contributed to study design and manuscript revision. KD performed statistical analysis and manuscript review. PK contributed to study design, conception and manuscript revision. 

Shohini Mukerji¹, D Thomas¹, L McDonald¹, D Chesher¹

¹Chemical Pathology Department, Royal North Short Hospital, St Leonards, NSW, Australia, NSW Health Pathology

Background 

In biochemistry departments, laboratory staff are typically responsible for the majority of internal quality control troubleshooting, result validation and communication of critical results. Our main laboratory supervises eight other laboratories, and it is a challenge to provide high quality ongoing education for staff with varying levels of experience across multiple sites. Among other formats, our laboratory has a fortnightly internal education program via oral presentations for staff at the main laboratory and is in the process of developing online modules for continuing education.

Biochemistry staff at our main laboratory, and other metropolitan and regional laboratories were surveyed to gauge the appeal and perceived effectiveness of different education formats. Staff with management responsibilities were also surveyed on their perception of the effectiveness of education formats. 

The education formats that staff prefer may vary over time depending on factors such as staff experience/qualification levels, evolving technology and the introduction of new responsibilities. Staff perceptions of the value of onsite and external education are reported occasionally in studies.1,2 There is however, limited literature on the format of internal education preferred by laboratory staff. This survey can assist with future improvements in the quality of continuing education programs for our staff.   

1.      Blagg LN, Hruban RH, Gehrie EA. A Department-Sponsored, Hospital-Based Pathology Education Symposium Is a Cost-Effective Method to Provide Laboratory Staff With Highly Rated Continuing Education Experiences. Arch Pathol Lab Med. 2021 Feb 1;145(2):231-239. 

2.      Novis DA, Nelson S, Blond BJ, Guidi AJ, Talbert ML, Mix P, Perrotta PL. Laboratory Staff Turnover: A College of American Pathologists Q-Probes Study of 23 Clinical Laboratories. Arch Pathol Lab Med. 2020 Mar;144(3):350-355.

Statement of Contribution 

SM devised the project plan and drafts of the abstract and poster. All other authors were involved in review and editing of content 

Owen Yi¹, Campbell Heron¹

¹Department of Chemical Pathology, LabPLUS, Auckland City Hospital, Auckland, New Zealand

Introduction: Roche Cobas measures free T4 (fT4) up to 100 pmol/L. Dilution is not an option, as it causes dissociation from binding proteins and non-linearity. We present a case of a 16yo F with amiodarone-induced thyrotoxicosis and persistent fT4 >100 pmol/L despite 10 days of treatment. A method was developed to extrapolate an estimated fT4 concentration and enable monitoring.

Methods: The principle of fT4 dissociation constant was used to determine the following relationship via serial dilution: y = n/x^k where n is the neat result, y are the results on dilution and x are the dilution factors. Log transformation into ln(n/y) = k*ln(x) produced a linear function with a slope of k. Since the neat value is unknown for samples >100 pmol/L, the process is modified to allow extrapolation of the neat result. Transformed linear relationship were consistently obtained on multiple samples tested including index patient’s samples.

Conclusion: We were able to extrapolate an estimated concentration for this patient and demonstrated improving fT4 with treatment. This method was also demonstrated to be applicable to free T3 dilution. We also briefly explored its application in identifying fT4 assay interferences, including the relationship between the neat value and the slope k.