Journal of Clinical Pathology

Paired-like homeobox 2B ( PHOX2B ) is a gene essential in the development of the autonomic nervous system. PHOX2B mutations are associated with neurocristopathies-Hirschsprung disease (HSCR) and congenital central hypoventilation syndrome (CCHS)-and peripheral neuroblastic tumours. PHOXB2 plays an important role in the diagnostics of these conditions.Genotyping of a PHOX2B pathogenic variant is required to establish a diagnosis of CCHS. In HSCR patients, PHOX2B immunohistochemical staining has proven to be a valuable tool in identifying this disease...

Phaeochromocytomas and paragangliomas are rare catecholamine-producing neuroendocrine tumours which can potentially cause catastrophic crises with high morbidity and mortality. This best practice article considers the causes and presentation of such tumours, screening and diagnostic tests, management of these patients and consideration of family members at risk.

No abstract text is available yet for this article.

While the overwhelming majority of colorectal carcinomas (CRC) are diagnosed as adenocarcinoma not otherwise specified, there are numerous under-recognised morphologic patterns of CRC. These patterns are recognised by the WHO, appear in reporting manuals for the American Joint Committee of Cancer, and/or are listed on synoptic reports, while many other variants have either fallen out of favour or are emerging as future bona fide patterns. Herein, we discuss 13 variants: serrated adenocarcinoma, micropapillary adenocarcinoma, medullary carcinoma, neuroendocrine carcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, adenosquamous carcinoma, adenoma-like adenocarcinoma, lymphoglandular complex-like CRC, carcinoma with sarcomatoid components, cribriform-comedo-type adenocarcinoma, undifferentiated carcinoma and low-grade tubuloglandular adenocarcinoma...

AIMS: The purpose of this study is to report novel and unusual USP6 fusion partners in aneurysmal bone cysts (ABCs). These findings may be useful in routine diagnostics as well as in studying the biology of USP6 -related disorders. METHODS: A cohort of seven patients diagnosed with ABC examined between 2014 and 2023 at Motol University Hospital in Prague was included into this retrospective non-randomised study. All cases were analysed using histopathological evaluation, immunohistochemistry and Anchored multiplex RNA methods...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

We demonstrate a method for tissue microdissection using scanning laser ablation that is approximately two orders of magnitude faster than conventional laser capture microdissection. Our novel approach uses scanning laser optics and a slide coating under the tissue that can be excited by the laser to selectively eject regions of tissue for further processing. Tissue was dissected at 0.117 s/mm2 without reduction in yield, sequencing insert size or base quality compared with undissected tissue. From eight cases, 58-416 mm2 of tissue was obtained from one to four slides in 7-48 seconds total dissection time per case...

Uroplakins are a family of membrane-spanning proteins highly specific to the urothelium. There are four uroplakin proteins in humans. These are encoded by the following UPK genes: UPK1A , UPK1B , UPK2 and UPK3 Uroplakin proteins span the apical membrane of umbrella cells of the urothelium, where they associate into urothelial plaques. This provides a barrier function to prevent passage of urine across the urothelium in the renal pelvis, ureters, and bladder. Uroplakins are also involved in developmental processes such as nephrogenesis...

AIMS: Accurate determination of histological activity in ulcerative colitis (UC) is essential given its diagnostic and prognostic importance. Data on the relationship between histology and immune cell markers are limited. We aimed to evaluate the association between histological disease activity and immune cell marker concentration in colonic biopsies from patients with UC. METHODS: Sigmoid colon biopsies from 20 patients with UC were retrospectively assessed using the Robarts Histopathology Index (RHI)...

AIMS: We investigated key signalling pathways' activity and mutational status of early-stage breast carcinomas with low and intermediate 21-gene recurrence score (RS) to identify molecular features that may predict recurrence. METHODS: This is a retrospective case-control study of 18 patients with recurrent breast carcinoma with low and intermediate 21-gene RS (<25) and control group of 15 non-recurrent breast cancer patients. DNA and mRNA were extracted from tumour tissue...

AIMS AND METHODS: Idiopathic multicentric Castleman disease (iMCD) is currently considered to be classified into three clinical subtypes, including idiopathic plasmacytic lymphadenopathy (IPL), thrombocytopaenia, anasarca, fever, reticulin fibrosis/renal dysfunction, organomegaly (TAFRO) and not otherwise specified (NOS). Among the three, iMCD-IPL closely mimics IgG4-related disease (IgG4-RD). In diagnosing IgG4-RD, it is sometimes challenging to distinguish iMCD-IPL patients that also meet the histological diagnostic criteria for IgG4-RD...

AIMS: Pre-surgical risk classification tools for prostate cancer have shown better patient stratification with the addition of cribriform pattern 4 (CC) and intraductal prostatic carcinoma (IDC) identified in biopsies. Here, we analyse the additional prognostic impact of CC/IDC observed in prostatectomies using Cancer of Prostate Risk Assessment post-surgical (CAPRA-S) stratification. METHODS: A retrospective cohort of treatment-naïve radical prostatectomy specimens from three North American academic institutions (2010-2018) was assessed for the presence of CC/IDC...

Identification of sentinel node (SN) metastases can set the adjuvant systemic therapy indication for stage III melanoma patients. For stage IIIA patients, a 1.0 mm threshold for the largest SN tumour diameter is used. Therefore, uniform reproducible measurement of its size is crucial. At present, the number of deposits or their microanatomical sites are not part of the inclusion criteria for adjuvant treatment. The goal of the current study was to show examples of the difficulty of measuring SN melanoma tumour diameter and teach how it should be measured...

An astute macroscopic examination, coupled with correlating the gross findings with clinical indication and operative notes along with judicious, yet all pertinent sectioning for pathological examination is crucial for an accurate histopathological diagnosis, eventually leading to optimal patient care. This succinct review highlights the general concepts that lay the foundation of evaluating and grossing specimens from the luminal gastrointestinal (GI) tract. We also discuss the gross evaluation and sectioning of small therapeutic resections, along with a systematic approach and rationale when grossing and submitting histological sections from larger oncological resections from the luminal GI tract...

Macroscopic specimen examination is often critical for accurate histopathology reporting but has generally received insufficient attention and may be delegated to inexperienced staff with limited guidance and supervision. This review discusses issues around macroscopic examination of some common urological specimens; highlighting findings that are critical for patient management and others that are clinically irrelevant. Macroscopic findings are of limited value in completely submitted radical prostatectomy specimens but may be critical in orchidectomy specimens where identification of focal non-seminomatous components can significantly impact patient management...

Pathological examination of surgical specimens and compilation of a surgical pathology report comprises a series of events which includes macroscopic examination and tissue sampling, either complete or selected. This step is critical but often overlooked in the literature and not given the attention it deserves. In this review, we discuss the macroscopic examination and grossing of gynaecological pathology specimens, with reference to national and international protocols. We provide guidance as to the degree of sampling necessary in different scenarios and stress that a common-sense approach is necessary with flexibility in the degree of sampling depending on a variety of factors...

The pathological assessment of a breast surgical specimen starts with macroscopic evaluation, arguably one of the most critical steps, as only a small percentage of the tissue is examined microscopically. To properly evaluate and select tissue sections from breast specimens, it is essential to correlate radiological findings, prior biopsies, procedures and treatment with the gross findings. Owing to its fatty nature, breast tissue requires special attention for proper fixation to ensure appropriate microscopic evaluation and performance of ancillary studies...

Macroscopic examination of surgical resections from the head and neck may be difficult due to the complex anatomy of this area. Recognition of normal anatomical structures is essential for accurate assessment of the extent of a disease process. Communication with the surgical team, correct specimen orientation and sampling are critical for assessment and the importance of radiological and clinical correlation is emphasised. Tumour involvement at each subsite is highlighted with reference to where there are implications on pathological staging and the potential need for adjuvant therapy...

BACKGROUND: Methylthioadenosine phosphorylase (MTAP) is an essential metabolic enzyme in the purine and methionine salvage pathway. In cancer, MTAP gene copy number loss ( MTAP loss) confers a selective dependency on the related protein arginine methyltransferase 5. The impact of MTAP alterations in gastrointestinal (GI) cancers remains unknown although hypothetically druggable. Here, we aim to investigate the prevalence, clinicopathological features and prognosis of MTAP loss GI cancers...