Diagnostic Histopathology最新文献

Histological assessment of a muscle biopsy is one of the most complex techniques which, currently in the UK, is only provided in very few specialist centres. This requires specialist laboratory skills in handling fresh tissue, freezing under optimal conditions, performing complex histochemical and immunohistochemistry staining on frozen tissue and specialist training for the histopathologists for interpretation and clinicopathological discussion. Access to electron microscopy and Genomic testing is also vital. This review will focus firstly on generic information on clinical indications, specimen handling, panel of histochemical and immunohistochemical stains and histological features of a normal paediatric muscle biopsy. The second section will focus on diagnostic features of a muscle biopsy specifically in the work-up of paediatric neuromuscular and metabolic conditions using case examples. The final section will focus on recent developments in genomic testing and the future prospects of muscle biopsy interpretation. Although complex, muscle biopsy interpretation is mentally stimulating and challenging, and it follows a schematic approach similar to medical liver or renal biopsies. In view of the complexity involved in procuring and handling the sample, muscle biopsy is usually not part of the early stages of work up. This makes it an extremely precious sample, but equally a rewarding exercise when histological interpretation provides the diagnosis and/or guides further genetic testing.

Basaloid neoplasms of the skin are often challenging not only to general pathologists but also dermatopathologists especially in the setting of partial sampling. While basal cell carcinomas make up most cutaneous neoplasms, there is a wide variety of both benign and malignant entities that have a basaloid morphology, which are particularly important to distinguish when present on skin in sensitive areas. Distinguishing between the malignant from the benign requires an understanding of the clinical presentation, histological correlation, emergence of new subclassification, as well as molecular discoveries. This chapter will examine the common cutaneous basaloid neoplasms encountered in routine practice and will highlight pitfalls to avoid misdiagnosis of rare but aggressive mimics.

The histopathological diagnosis of lichenoid dermatosis in the anogenital area is challenging. A wide range of conditions can display this pattern, often with overlapping features. Understanding clinicopathological characteristics, key histological clues and potential misleading appearances is crucial for an accurate diagnosis. Common entities like lichen planus or lichen sclerosus can vary in appearance depending on the specific variant or stage of evolution. Additionally, certain pathologies can closely mimic other conditions. For example, syphilis or paraneoplastic pemphigus may present changes identical to lichen planus, while "Mycoplasma pneumoniae-induced rash and mucositis" and paraneoplastic pemphigus can simulate erythema multiforme. Unusual patterns can also arise in cases of lichenoid contact dermatitis or condyloma lata in secondary syphilis. The presence of a plasma cell-rich lichenoid infiltrate serves as a clue for diagnosing plasma cell mucositis (Zoon) and syphilis. However, it is important to note that plasma cells may be outnumbered by lymphocytes in the former or completely absent in the latter. Therefore, in such cases, being aware of other subtle changes and recognizing the characteristics of the clinical presentation is crucial for arriving at the correct diagnosis. This review summarises practical information to empower the diagnostic precision of these challenging conditions.

Pigmented lesions of the vulva and vagina occur commonly and can be challenging both clinically and microscopically. Vulvovaginal melanotic macules are the most common pigmented vulvar lesion. Mucosal vitiligo can be confined to the anogenital region. Acquired melanocytic nevi of the vulva comprise approximately 10%–12% of pigmented vulvar lesions. Blue and Spitz (spindled and epithelioid cell) nevi can occur rarely in the vulvovaginal area. Although pigmented and lentiginous in histologic appearance, melanocytic lesions associated with lichen sclerosus have a “trizonal” pattern of growth, similar to recurrent nevi, which can be helpful in distinguishing them from melanoma. Atypical genital nevi are symmetrical and circumscribed and are typically comprised of confluent growth of nests of melanocytes with variable size and shape and melanocytes demonstrate uniform cytologic atypia. In contrast to dysplastic nevi, atypical genital nevi often do not have a prominent host response and display a broad pattern of fibrosis instead of fibrolamellar fibrosis. Nuclear immunostains such as Sox10 and MiTF can be very helpful in assessing the margins of vulvar melanoma which frequently are multifocal. Recognition of these features can be helpful in classifying the pigmented lesions of the vulva.

Spindle cell and fibrohistiocytic soft tissue tumours are a diverse group of neoplasms that are commonly seen in childhood. This paper provides an overview of the histopathological features of the more common entities that are likely to be encountered by general pathologists and paediatric pathologists in children and young adults. Fibroblastic and myofibroblastic tumours are characterized by the proliferation of fibroblasts or myofibroblasts, and they exhibit a wide range of histological appearances, from benign to malignant, and can occur in various anatomical locations. Nerve sheath tumours are derived from the Schwann cells of the peripheral nerves and are often associated with neurofibromatosis. Synovial sarcoma, a high-grade malignant tumour, is characterized by specific chromosomal translocations resulting in the SS18-SSX fusion gene. NTRK-rearranged tumours, a recently recognized entity, are characterized by gene fusions involving the neurotrophic tyrosine receptor kinase (NTRK) genes, leading to overexpression of the TRK protein. Fibrohistiocytic tumours of childhood, including fibrous histiocytoma and plexiform fibrohistiocytic tumour, show varying degrees of fibroblastic and histiocytic differentiation. They exhibit a wide range of clinical behaviour, from benign to locally aggressive. Understanding the histopathological features of these tumours is important to guide appropriate management. This review provides an overview of these features, along with the latest advances in molecular pathology, which can aid the pathologist in making a diagnosis.

Soft tissue sarcomas are a rare group of heterogenous entities which affect the tissues supporting, connecting and/or surrounding body structures and organs. Factors such as patient age and tumour location can influence how soft tissue sarcomas manifest with biological and clinical behaviour ranging from less aggressive to highly malignant. Recent advances in both diagnosis and treatment have led to new insights into the pathologic, histologic and genomic characterisation of sarcomas and these insights have diversified subtyping. One subtype, small round (blue) cell tumours (SRBCT), constitutes a divergent group of tumours which occur most commonly in the paediatric and young adult population. The clinical characteristics, prognostics and therapeutic approaches regarding these tumours differ greatly. Despite this variation the relative histomorphological uniformity of SRBCTs poses the histopathologist a diagnostic challenge. This challenge is being ameliorated by advances in molecular genetic profiling which is revolutionising diagnosis and providing insight into both biomarkers and therapeutic targets. The following review aims to address the pertinent morphological, immunohistochemical and molecular features of some of the more common SRBCTs, including variants, and hopes to provide the histopathologist with a diagnostic approach focussed upon the key diagnostic features.

We discuss a case of a paediatric low grade glioma where the integrated diagnosis was a diffuse astrocytoma with MYB or MYBL1 alteration. Surgical excision of the tissue revealed a low grade tumour appearance with small round nuclei and fine fibrillary cytoplasm. MYB or MYBL1-alteration was shown on methylation array analysis. MYB and MYBL1 are transcriptional transactivators that have important roles in cell proliferation, and their overexpression can lead to tumour formation. The diagnosis of novel subtypes of paediatric low-grade gliomas is now possible due to the increasing role of molecular pathology.

Placental inflammatory conditions comprise a main diagnostic category in placental pathology. Placental inflammation can broadly be categorised into acute and chronic, with co-existence of both in the same placenta also possible. Chronic inflammation may be of infectious or non-infectious aetiology. TORCH infections represent the majority of placental infections associated with chronic inflammation in developed countries. Non-infectious chronic placental inflammatory conditions, such as villitis of unknown aetiology (VUE) and chronic histiocytic intervillositis (CHI) are currently attributed to immune-mediated mechanisms and aetiology, and have been associated with significant implications such as miscarriage, stillbirth, premature delivery, intra-uterine growth restriction, poor neurological outcome in living babies, and recurrence risk in future pregnancies. Standardised histologic diagnostic criteria have been proposed for the diagnosis of VUE, whereas a standardised histologic definition is currently lacking for CHI, hampering the comparison between different studies and hindering reaching conclusions about the effectiveness of different treatment strategies. This review will discuss inflammatory conditions of the placenta with emphasis on histopathological diagnosis, clinical associations, and implications for future clinical care.

Despite being one of the most frequent solid tumours in children, renal tumours are uncommon. Their accurate diagnosis and staging are essential for the appropriate treatment because they comprise a variety of entities with a broad spectrum of clinical, histological, molecular biology, and prognostic features. Wilms tumour (WT) accounts for 80–85% of renal tumours of childhood, whereas other tumours including mesoblastic nephroma, clear cell sarcoma, rhabdoid tumour, renal cell carcinoma, and others are extremely uncommon (up to 2%–4% each), which explains why they pose a significant diagnostic challenge for pathologists. There are two major study groups with different treatment approaches but very comparable outcomes. The International Society of Paediatric Oncology approach (followed in most of the world) is based on preoperative chemotherapy, followed by surgery and further therapy, whereas the Children's Oncology Group approach (followed mainly in the United States and Canada) is based on primary surgery, followed by postoperative treatment. In both study groups for WT the most important prognostic factors are histological type and stage. The criteria for subtyping and staging are similar but still differ between the study groups, making a direct comparison impossible, but nevertheless, the outcomes are remarkably similar. The chapter provides an update on pathology, recent molecular discoveries and prognosis in paediatric renal tumours.

Detection and management of endometrial precancers remain ongoing challenges in the fields of pathology and gynecology, with implications for the need to decrease mortality from endometrial cancer. Due to many factors, the diagnosis of endometrial precancers and their reliable discrimination from benign mimics remains a difficult area in diagnostic pathology, and among the most frequently encountered in gynecologic pathology. Our understanding of endometrial precancers and their diagnosis has been enhanced by systematic investigations into morphologic criteria, the molecular genetics of endometrial cancer and their precursors, and the validation of individual markers. Despite these refinements, many ambiguous cases are encountered in daily practice, creating diagnostic uncertainty and suboptimal patient management. Recently, an immunohistochemical 3-marker panel consisting of β-catenin, PAX2, and PTEN has been proposed as a diagnostic adjunct. While the panel is useful in routine practice in the majority of cases, these immunostains—like any others—have nuances in their interpretation and require an understanding of normal vs. aberrant patterns of expression. Here, we review criteria for scoring each of the 3 markers and provide a case-based review that serves as a guide for how these markers can be diagnostically helpful in a range of clinical scenarios.