Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology

Malpractice in head and neck cancer: a comprehensive medico-legal review

2025-02-17T13:04:29+00:00

Head and neck (H&N) malignancies include a broad spectrum of clinical presentations and outcomes. Sources of risks, errors and mistakes are intrinsic to every therapeutical-diagnostic step leading to potential burden of malpractice allegations and threaten delivery of healthcare. The purpose of this review is to report key factors of malpractice litigation H&N neoplasms, analyzing its ethical-deontological and medico-legal aspects with a focus on Italian law. PubMed and Scopus databases were accessed to assess existing cases of oncological H&N malpractice. Twelve articles were identified according to search criteria in the selected period (2000-2024). Inclusion criteria lead to 6 articles pertaining to analysis of allegations of malpractice in H&N tumors. Diagnostic delay and informed consent issues are the most represented allegations. Poor access and lack of standardization in legal databases is commonly seen as a factor that holds back a thorough litigation analysis. This review adds evidence about common features of medical malpractice allegations through a medico-legal perspective that may help in adopting preventive strategies to mitigate risks and enhance patient safety. Combining data deriving from different studies, the paper contributes to understand the evolution of the trajectory of malpractice in this field.

Immunotherapy in recurrent/metastatic head and neck squamous cell carcinoma: PD-L1 and beyond

2025-05-20T16:35:38+00:00

Head and neck squamous cell carcinoma (HNSCC) is a prominent global health concern because of its high incidence, aggressive clinical behavior, and scarce therapeutic options. The management of these neoplasms in the recurrent/metastatic setting has been revolutionized following the results of key clinical trials, leading to the advent of immunotherapeutic agents targeting the PD-1/PD-L1 axis. Despite the exciting results obtained with the new drugs, immunotherapy is helpful only in a sizable minority of patients, and there is a pressing need to identify reliable predictive biomarkers for patient selection. The immunohistochemical assessment of PD-L1 expression was initially identified as a powerful and easily accessible predictive tool, and gained its place as the current standard for patient selection, but it has clear limitations. The imperfect predictive power of PD-L1 has resulted in a strong effort to discover additional clinical, pathological and molecular biomarkers such as tumor HPV status, mutational burden, microsatellite instability, and much more. In addition, the tumor microenvironment has been extensively studied searching for promising new biomarkers as potential avenues for refining patient selection and improvement of treatment outcomes. As we gain deeper understanding of the complex interplay between tumor biology, immune system, and tumor microenvironment, we are rapidly realizing that the perfect biomarker, the magic bullet, probably doesn’t exist. On the other hand, with the introduction of new drugs on the horizon, integration of multiple variables in the context of combined predictive scores is shaping up to be our best weapon in this strife to treat each patient with the best possible drug.

Cell-mediated mucositis of the oral cavity: narrative review on etiology, clinicopathological aspects and malignant transformation

2025-05-20T16:47:27+00:00

Cell-mediated mucositis is the expression of a type IV hypersensitivity, in which cytotoxic CD8+ T lymphocytes attack the keratinocytes of the basal layer responsible for activating the immune response. There is sufficient evidence for an increased risk of oral cancer in patients with a diagnosis cell mediated mucositis. This review aims to examine the etiology, clinical-histological features, management and malignant transformation of a group of cellmediated mucositis, including oral lichen planus, oral lichenoid lesions, Graft versus host disease, oral lesion of lupus erythematous. The authors conducted a literature review, selecting relevant studies based on their novelty, applicability, and impact. The text highlights the varying rates of malignant transformation associated with different oral conditions. For oral lichen planus, the risk of transformation ranges from 0.44% to 2.28%, while for oral lichenoid lesions (OLLs), the rate is slightly higher, between 1.20% and 3.80%. Conditions like graft-versus-host disease are linked to a malignant transformation rate of 3.47%, and oral lesions associated with lupus erythematosus carry a similar risk at 3.3%, often involving squamous cell carcinoma of the lips. In cases of oral epithelial dysplasia, the risk increases significantly with severity, reaching 24.1% for severe dysplasia. The condition with the highest malignant potential is proliferative verrucous leukoplakia, with a transformation rate estimated at 49.5%. These findings underscore the importance of accurate diagnosis, vigilant monitoring, and the development of new therapeutic strategies. Recent advancements in treatments, such as nivolumab and imiquimod, show promise in early trials. These approaches aim to move beyond passive observation, shifting towards personalized medical interventions to reduce the risk of malignant transformation in high-risk patients.

Head and neck synovial sarcoma in a woman with previous lymphoma and papillary thyroid carcinoma

2025-05-20T18:06:59+00:00

Synovial sarcoma is a rare malignant mesenchymal neoplasm that rarely arises in the head and neck and thyroid lodge. Researchers have documented only few cases in the literature. We present the case of a young woman diagnosed with synovial sarcoma that originated in the thyroid region one year after a total thyroidectomy for a primary papillary carcinoma and eight years after chemo-radiotherapy for a lymphoma.

Evaluation of papillary thryoid carcinoma and its variants: multifocality in thyroid lobectomy and completion thyroidectomy - a single tertiary center retrospective study

2025-05-20T16:56:57+00:00

Aims. The American Thyroid Association (ATA) updated guidelines for the treatment of thyroid cancer, leading to a less aggressive approach depending on clinical-pathological features. As a result, the possibility to perform lobectomy versus total thyroidectomy has significantly increased. The majority of thyroid cancers are indolent with an excellent prognosis, while only 15% of patients with well-differentiated carcinoma, including papillary thyroid carcinoma (PTC), have locally advanced thyroid cancer (LATC) at diagnosis. We reviewed our practice in treating thyroid carcinoma over the last decade.
Methods. From January 2010 to December 2020, 1057 patients with uninodular benign and malignant thyroid lesions were reviewed. Results. Among these cases, 77% were women with a median age of 49.3 years. The series involved 307 malignant diagnoses (29.05%) including 196 (61.6%) classic PTC and 38 (12%) aggressive variants of PTC, mostly tall cell variant (30 cases, 9.4%). Among malignant cases, multifocality was microscopically documented in 84 cases (26.4%). Using the ATA distribution of risk, there were 239 cases in the low risk and 68 in the intermediate risk categories. Second surgery was assessed in a total of 150 cases, showing 42 cases with additional thyroid cancer foci in the other lobe (26 single vs 16 multiple foci). Ten cases had metastatic perithyroidal lymph nodes.
Conclusion. Our data could be the basis for performing a longitudinal study in order to establish which risk factors can predict bilateral involvement and to suggest a tailored surgical approach.

KRAS/NRAS variants and copy number alterations prognostically stratify patients with sinonasal melanoma

2025-05-20T17:09:44+00:00

Sino-nasal mucosal melanoma (SN-MM) is an aggressive and rare form of melanoma arising from mucosal melanocytes with pathogenesis unrelated to sun exposure. Conversely to cutaneous melanoma (CM), the molecular bases underling SN-MM development and progression are unclear, and no molecular predictive markers have been identified yet. To better define the molecular landscape of SN-MM, a retrospective series of 37 SN-MMs from 31 patients was analysed for both somatic mutations and cytogenetic alterations. The somatic mutation analysis identified the presence of a driver gene pathogenic variant in 54% of cases. In detail, mutually exclusive NRAS mutations were found in 42% of cases, KRAS mutations in 6%, and KIT mutations in 6% of cases. Remarkably, no BRAF mutations were detected. Patients with NRAS-mutated/KRAS-wild type (wt) melanomas showed better outcome than patients with NRAS-wt/KRAS-mutated melanomas, which were associated with multiple recurrences at local or regional sites. On the other hand, focusing on genomic alterations, copy number variants (loss of 1p36, loss of 3p/3q) were identified in 19% of SN-MMs, which showed poor overall survival and short disease-free survival with early metastatic dissemination. This work describes a new integrated characterization of both single nucleotide variants and, for the first time, genomic alteration in SN-MM, providing a new insight into molecular bases of these neoplasms and prompting further efforts for personalized clinical protocols according to tumour aggressiveness.

Head and neck hematolymphoid proliferations: what is new?

2025-04-06T09:20:11+00:00

In 2024, the World Health Organization published its 5th edition of tumor classification, which comprises several updates and modifications in the “blue book” focused on head and neck tumors. These changes feature a systematized and expanded discussion on haematolymphoid proliferations using a multi-parameter approach that comprises clinical features, morphology, immunophenotype, and genetic data, with the latter becoming an essential characteristic for classification. Moreover, for the first time, the World Health Organization has included non-neoplastic diseases, such as reactive lymphoid proliferations, alongside several recognized independent disorders, including Epstein-Barr Virus positive mucocutaneous ulcers and IgG4-related diseases. Also, various neoplastic diseases, such as paediatric-type follicular lymphoma and large B-cell lymphoma with IRF4 rearrangement, are recognized as independent entities. Finally, the focus has expanded to include different types of histiocytic neoplasms. This review examines and illustrates the main changes and updates on hematolymphoid proliferation and neoplasia in the Head and Neck chapter of the 5th Edition of the Head and Neck WHO classification.

When to think of Sarcina sp. in histopathologic examination of gastrointestinal tract: insights from a one-year-old with esophagitis and gastric outlet obstruction

2025-05-21T08:14:02+00:00

Dear Editor-in-Chief,

Sarcina ventriculi is a Gram-positive, anaerobic coccus that is rarely encountered by pathologists in biopsy specimens. Despite its infrequency, its distinct histopathological characteristics facilitate the diagnosis when thoroughly investigated. In this report, we present a case of a 1-year-old patient who had a history of vomiting and diagnosed with gastric outlet obstruction via endoscopy. We emphasize the important histopathological and clinical features that should prompt pathologists to consider this organism in their differential diagnoses.

A 1-year-old girl was admitted to the emergency department due to a 10-day history of projectile vomiting, which had worsened in recent days. Upon admission, physical examination and laboratory results – including complete blood count, renal function tests, serum electrolytes, bilirubin, and amylase – were within normal limits. Mild elevations were noted in SGOT and SGPT (58 U/L and 63 U/L, respectively).

Ultrasound imaging revealed gastric expansion and delayed gastric emptying. An esophagogastroduodenoscopy (EGD) demonstrated furrowing and inflamed mucosa in the esophagus, with additional findings of inflamed gastric mucosa and gastric outlet obstruction that prevented the scope from advancing to the duodenum.

Histopathological examination of H&E-stained slides revealed acute esophagitis featuring cuboid pockets of organisms arranged in clusters of 4, 8, and more, consistent with Sarcina sp. bacteria. These organisms were also observed on the mucosal surface of the antral gastric mucosa. Notably, Helicobacter pylori was not identified in the gastric specimen (Fig. 1)

A 20th century case of noma infection following typhoid fever from the Morgagni Museum (Padua, Italy)

2025-05-20T19:46:52+00:00

Noma is a potentially fatal, gangrenous disease that leads to tissue destruction in the face. It has been proven to develop mostly in children living in extreme poverty. There is a lack of data regarding microbiological analysis of the ulcers, making the knowledge of the bacteria involved and its etiology still unclear. Within this framework, pathological specimens from museological collections could offer relevant improvements for the comprehension of etiology of noma. The Morgagni Museum of Human Anatomy in Padua hosts a unique case of noma dating back to 1902, and two related specimens, a mesenteric lymphatic ganglion and a spleen. The bacteriological analysis of the Museum’s case showed the presence of Typhus bacilli in the patient’s cheek and led to hypothesize the correlation between typhoid infection and noma.
The specimens coming from historical collections may lead to better knowledge about etiology of noma, and potentially prevent its invalidating sequelae.

Biopsy in chronic liver disease: proposal for a shared path between clinicians and pathologists

2025-05-20T18:14:15+00:00

Introduction. Liver biopsy is fundamental for characterizing chronic liver disease. Effective communication between specialists during the diagnostic process is crucial. This project aims to outline a diagnostic path shared by clinicians and pathologists, and to propose practical solutions at different stages of the diagnostic work-up, from clinical suspicion to the histology report in patients with chronic liver diseases.
Methods. A panel of experts, within the methodological framework of lean management, joined two rounds of discussion sharing their professional experiences. They reached an agreement on the essential phases and actions of the diagnostic process, and built a shared diagnostic workflow.
Results. The panel agreed on the importance of a standardized form to be filled with all relevant clinical and laboratory data to ensure the flow of information between the clinician and the pathologist. Further decisions were reached on the following practical issues: the advantage of performing liver biopsies in dedicated centers, the need for homogeneous procedures, and the minimum quality standards in all phases, including reporting. Finally, the panel agreed on the usefulness of digital pathology to exchange observations and opinions and to create a territorial network to discuss challenging cases.
Conclusion. Sharing a diagnostic path between the pathologist and the clinician can be a powerful tool to improve both the timing and accuracy of the histology report.

One protocol to rule them all: a pilot study to identify the best fixation and decalcification approach for bone marrow biopsy immunohistochemistry

2025-05-20T19:38:09+00:00

Objective. Standardization of the pre-analytical phases of bone marrow trephine biopsy (BM) has yet to be achieved. In particular, several fixative and decalcifying reagents with specific benefits and drawbacks are described, but only a few direct comparisons are available. This study aims to test the most used fixation and decalcification protocols and evaluate their effect on tissue antigenicity via immunohistochemistry (IHC).
Methods. To avoid damaging and exhausting diagnostic BMs, we used “surrogate” BMs obtained from dedicated grossing of a non-pathologic spleen. Eleven fixation and decalcification protocols were tested, and their performances were evaluated via IHC protein expression of 25 biomarkers.
Results. The IHC yield varied based on the fixative and decalcifying reagents, but the overall quality is mainly related to the fixative rather than the decalcifying phases. The protocol with the lowest number of inadequate IHC stains (5 out of 25) combined commercially available B5-based fixative and EDTA-based decalcifying reagents. The worst metrics (8 inadequate IHC stains out of 25) were obtained with a protocol based on “inhouse” B5-based and EDTA-based reagents.
Conclusions. We compared different protocols and found the best combination of fixative and decalcifying reagents for accurate IHC staining. These findings can improve bone marrow sample handling and standardization in pathology laboratories.

Cholesterol granuloma. Another brick in the wall of mediastinal lesions

2025-05-21T08:48:50+00:00

Dear Editor-in-Chief,

A 57-year-old man underwent about two years ago a coronary arterial bypass and a total thyroidectomy for ischemic heart disease and diffuse multinodular goitre, respectively. A routine follow-up cardiac magnetic resonance imaging (MRI) revealed the presence of a newly developed, expansive lesion in the anterior mediastinum. This lesion was further investigated by total body computed tomography (CT) scan, which showed a 22x20 mm mediastinal lesion, with a lymph node measuring 8 mm in maximum diameter within the adjacent fat tissue. A further MRI confirmed the presence of both mediastinal and lymph node findings, raising the strong suspicion of heteroplastic lesion.

A tricky nasal polyp

2025-05-21T07:19:55+00:00

Leishmaniasis is an infectious disease caused by a protozoon of the genus Leishmania. It can manifest as cutaneous, mucosal, localized lymphadenitis forms or it can result as multiorgan involvement. In this article we present the case of a 59-year-old male with a polypoid mass attached to the septum at the right nasal cavity and symptoms as nasal congestion, hyposmia and anterior rhinorrhea. Histological sections of the mass showed oval-shaped inclusions in the cytoplasm of histiocytes suspicious for Leishmania amastigotes. The diagnosis was confirmed by detection of Leishmania complex DNA with polymerase chain reaction (PCR).

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion: report of two cases with different clinical presentation

2025-05-21T07:27:26+00:00

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (M/LNeo- TK) such as PDGFRA, PDGFRB, FGFR1, JAK2, FLT3 rearrangement and ETV6::ABL1 fusion include rare and heterogeneous clinical-pathological entities with some similarities, not always associated with peripheral eosinophilia. Accurate diagnosis and demonstration of the specific genetic substrate have important implications since target therapy is possibly available. Herein we report two cases showing different bone marrow features and clinical presentation. Recognition of eosinophilic granuloblasts prompted genetic analysis that showed PDGFRB (case 1) and PDGFRA (case 2) gene rearrangement. Diagnosis of M/LN-eo-TK may be challenging. Pathologists may be the first professionals to suspect the disorder and should be aware of the therapeutic implication. Accurate BOM marrow evaluation with a panel of immunohistochemical reactions, and specific molecular analyses are required for proper diagnosis.

Eosinophilic vacuolated tumor of the kidney can have distant metastasis: a histo-molecular case study

2025-05-21T08:06:09+00:00

Eosinophilic vacuolated tumor (EVT) is an emerging renal entity and further studies are required to characterize this neoplasm. EVT is considered generally indolent because metastasis or death from the disease has never been reported. Herein, we report the first case of EVT with mediastinal lymph node metastasis to validate its at least borderline behavior. Based on the morphological features, we additionally used a large panel of immunohistochemical antibodies and next-generation sequencing (NGS) to confirm the diagnosis of EVT and exclude other renal entities. This case report highlights the notion that EVT can exhibit mediastinal lymph node metastasis and patients with EVT need to be closely followed.