Histopathological Analysis of Nodal Disease After Chemoradiation Reveals Viable Tumor Cells as the most Important Prognostic Factor in Head and Neck Squamous Cell Carcinoma, DOI 10.1007/s12105-023-01557-7

Letter to the edito

Genomic alterations and diagnosis of renal cancer

The application of molecular profiling has made substantial impact on the classification of urogenital tumors. Therefore, the 2022 World Health Organization incorporated the concept of molecularly defined renal tumor entities into its classification, including succinate dehydrogenase-deficient renal cell carcinoma (RCC), FH-deficient RCC, TFE3-rearranged RCC, TFEB-altered RCC, ALK-rearranged RCC, ELOC-mutated RCC, and renal medullary RCC, which are characterized by SMARCB1-deficiency. This review aims to provide an overview of the most important molecular alterations in renal cancer, with a specific focus on the diagnostic value of characteristic genomic aberrations, their chromosomal localization, and associations with renal tumor subtypes. It may not yet be the time to completely shift to a molecular RCC classification, but undoubtedly, the application of molecular profiling will enhance the accuracy of renal cancer diagnosis, and ultimately guide personalized treatment strategies for patients

Speicheldrüsenkarzinome – ein aktueller Überblick : Fortschritte in der molekularen Typisierung: Teil I

Zusammenfassung In den letzten Jahren hat die Charakterisierung der Speicheldrüsenkarzinome einen großen Wandel durchlebt. Morphologisch definierte Entitäten konnten zu einem Großteil auch molekular mit einem oftmals distinkten Genotyp charakterisiert werden. Der erste Teil des Artikels gibt einen Überblick über die Fortschritte der molekularen Charakteristiken des Mukoepidermoidkarzinoms, adenoid-zystischen Karzinoms, Azinuszellkarzinoms, des sekretorischen und intraduktalen Karzinoms sowie des hyalinisierenden klarzelligen Karzinoms. Der molekulare Genotyp kann dabei insbesondere bei der Klassifizierung ungewöhnlicher morphologischer Varianten von großem Nutzen sein. Rekurrente NTRK- oder RET-Genfusionen können dabei nicht nur als diagnostisches Hilfsmittel, sondern auch für eine potenzielle gezielte Therapie genutzt werden. Abstract In recent years, the characterization of salivary gland tumors has undergone a major transformation. Morphologically defined entities could to a large extent also be characterized molecularly with an often distinct genotype. The first part of this article reviews the advances in the molecular characteristics of mucoepidermoid carcinoma, adenoid cystic carcinoma, acinic cell carcinoma, secretory carcinoma, intraductal carcinoma, and hyalinizing clear cell carcinoma. The molecular genotype can be particularly useful in classifying unusual morphologic variants. Recurrent NTRK or RET gene fusions can be used not only as a diagnostic tool but also for potential targeted therapy

Differentiated Papillary NUT Carcinoma: An Unexpected, Deceptively Bland Presentation of a Sinonasal Carcinoma

BACKGROUND In recent years, the list of tumor entities in the sinonasal tract has significantly expanded, requiring advanced diagnostic testing. We report the case of a 32-year-old patient with an unusual NUT carcinoma originating in the maxillary sinus, which showed extensive well-differentiated, papillary squamous morphology, similar to the spectrum of the recently described DEK::AFF2 fusion-associated carcinoma. METHODS We performed immunohistochemical and molecular studies including EBV- and HPV-testing, as well as DNA/RNA next generation sequencing. RESULTS The tumor showed predominantly exophytic papillary growth with mature squamous differentiation. An additional component harbored atypical, less differentiated basaloid tumor cells with infiltration of the adjacent stroma. Conspicuous inflammation was evident. There was no evidence of HPV DNA or EBV RNA. Next-generation sequencing revealed a NUT::NSD3 gene fusion corresponding to ("speckled-type") immunopositivity of NUT in the tumor cells. CONCLUSIONS We describe a NUT::NSD3 gene fusion-associated NUT carcinoma of the sinonasal tract with a deceptively well-differentiated papillary growth pattern, thus expanding the morphological spectrum of this typically poorly differentiated neoplasm

Differentiated Papillary NUT Carcinoma: An Unexpected, Deceptively Bland Presentation of a Sinonasal Carcinoma.

BACKGROUND In recent years, the list of tumor entities in the sinonasal tract has significantly expanded, requiring advanced diagnostic testing. We report the case of a 32-year-old patient with an unusual NUT carcinoma originating in the maxillary sinus, which showed extensive well-differentiated, papillary squamous morphology, similar to the spectrum of the recently described DEK::AFF2 fusion-associated carcinoma. METHODS We performed immunohistochemical and molecular studies including EBV- and HPV-testing, as well as DNA/RNA next generation sequencing. RESULTS The tumor showed predominantly exophytic papillary growth with mature squamous differentiation. An additional component harbored atypical, less differentiated basaloid tumor cells with infiltration of the adjacent stroma. Conspicuous inflammation was evident. There was no evidence of HPV DNA or EBV RNA. Next-generation sequencing revealed a NUT::NSD3 gene fusion corresponding to ("speckled-type") immunopositivity of NUT in the tumor cells. CONCLUSIONS We describe a NUT::NSD3 gene fusion-associated NUT carcinoma of the sinonasal tract with a deceptively well-differentiated papillary growth pattern, thus expanding the morphological spectrum of this typically poorly differentiated neoplasm

Histopathological Analysis of Nodal Disease After Chemoradiation Reveals Viable Tumor Cells as the most Important Prognostic Factor in Head and Neck Squamous Cell Carcinoma

BACKGROUND In head and neck squamous cell carcinoma (HNSCC), salvage neck dissection (ND) is required after primary chemoradiation in case of residual nodal disease. Upon histopathological examination, viability of tumor cells is assessed but little is known about other prognostic histopathological features. In particular, the presence of swirled keratin debris and its prognostic value is controversial. The aim of this study is to examine histopathological parameters in ND specimens and correlate them with patient outcome to determine the relevant parameters for histopathological reporting. MATERIALS AND METHODS Salvage ND specimen from a cohort of n = 75 HNSCC (oropharynx, larynx, hypopharynx) patients with prior (chemo) radiation were evaluated on H&E stains for the following parameters: viable tumor cells, necrosis, swirled keratin debris, foamy histiocytes, bleeding residues, fibrosis, elastosis, pyknotic cells, calcification, cholesterol crystals, multinucleated giant cells, perineural, and vascular invasion. Histological features were correlated with survival outcomes. RESULTS Only the presence / amount (area) of viable tumor cells correlated with a worse clinical outcome (local and regional recurrence-free survival, (LRRFS), distant metastasis-free survival, disease-specific survival, and overall survival, p < 0.05) in both the univariable and multivariable analyses. CONCLUSION We could confirm the presence of viable tumor cells as a relevant negative prognostic factor after (chemo) radiation. The amount (area) of viable tumor cells further substratified patients with worse LRRFS. None of the other parameters correlated with a distinctive worse outcome. Importantly, the presence of (swirled) keratin debris alone should not be considered viable tumor cells (ypN0)

Clinical, Radiological, and Pathological Diagnosis of Fibro-Osseous Lesions of the Oral and Maxillofacial Region: A Retrospective Study

BACKGROUND: Fibro-osseous lesions (FOL) of the jaw represent a rare, benign group of lesions that share similar clinical, radiological, and histopathological features and are characterized by progressive, variable replacement of healthy bone tissue by fibrous connective tissue. METHODS: This retrospective study aimed to evaluate the incidence of fibro-osseous lesions and to reassess the efficacy of case-specific treatment management from a clinical, radiological, and histopathological perspective based on 14 years of data. RESULTS: Forty-four patients with a radiological and/or histopathological diagnosis of benign FOLs were identified and re-evaluated. Cemento-osseous dysplasia was the most common group of FOLs present in our patient cohort (45%), followed by ossifying fibroma (39%) and fibrous dysplasia (16%). The diagnostic imaging technique of choice was CBCT (68%), followed by PAN (18%), with most patients (95 %) additionally undergoing biopsy. The mean age of the patients at the time of diagnosis was 40.54 ± 13.7 years, with most lesions being located in the mandible (86%), with females being predominantly affected (73%). CONCLUSION: An interdisciplinary approach that analyzes all case-specific factors, including demographic data, medical history, intraoperative findings, and, most importantly, histopathological and radiological features, is essential for an accurate diagnosis and key to avoiding inappropriate treatment

The Morphological Spectrum of Papillary Renal Cell Carcinoma and Prevalence of Provisional/Emerging Renal Tumor Entities with Papillary Growth

Renal cell carcinoma (RCC) represents a heterogeneous disease, encompassing an increasing number of tumor subtypes. Post-2016, the World Health Organization (WHO) classification recognized that the spectrum of papillary renal cell carcinoma is evolving and has long surpassed the dichotomic simplistic "type 1 versus type 2" classification. The differential diagnosis of pRCC includes several new provisional/emerging entities with papillary growth. Type 2 tumors have been cleared out of several confounding entities, now regarded as independent tumors with specific clinical and molecular backgrounds. In this work we describe the prevalence and characteristics of emerging papillary tumor entities in two renal tumor cohorts (one consisting of consecutive papillary tumors from a single institute, the other consisting of consultation cases from several centers). After a review of 154 consecutive pRCC cases, 58% remained type 1 pRCC, and 34% type 2 pRCC. Papillary renal neoplasm with reversed polarity (1.3%), biphasic hyalinizing psammomatous RCC (1.3%), and biphasic squamoid/alveolar RCC (4.5%) were rare. Among 281 consultation cases, 121 (43%) tumors had a dominant papillary growth (most frequently MiT family translocation RCCs, mucinous tubular and spindle cell carcinoma and clear cell papillary RCC). Our data confirm that the spectrum of RCCs with papillary growth represents a major diagnostical challenge, frequently requiring a second expert opinion. Papillary renal neoplasm with reversed polarity, biphasic hyalinizing psammomatous RCC, and biphasic squamoid/alveolar RCC are rarely sent out for a second opinion, but correct classification and knowledge of these variants will improve our understanding of the clinical behavior of renal tumors with papillary growth

Correlation of dynamic contrast-enhanced bone perfusion with morphologic ultra-short echo time MR imaging in medication-related osteonecrosis of the jaw

OBJECTIVES: To investigate whether dynamic contrast-enhanced (DCE)-MR bone perfusion could serve as surrogate for morphologic ultra-short echo time (UTE) bone images and to correlate perfusion with morphologic hallmarks in histologically proven foci of medication-related osteonecrosis of the jaw (MRONJ). METHODS: Retrospective study including 20 patients with established diagnosis of MRONJ. Qualitative consensus assessment of predefined jaw regions by two radiologists was used as reference standard using Likert scale (0-3) for standard imaging hallmarks in MRONJ (osteolysis, sclerosis, periosteal thickening). DCE-MRI measurements performed in corresponding regions of the mandible were then correlated with qualitative scores. Regions were grouped into "non-affected" and "pathologic" based on binarized Likert scores of different imaging hallmarks (0-1 vs 2-3). DCE-MRI measurements among hallmarks were compared using Mann-Whitney-U-testing. ROC (receiver-operating-characteristic) analysis was performed for each of the perfusion parameters to assess diagnostic performance for identification of MRONJ using morphologic ratings as reference standard. RESULTS: Median perfusion measurements of "pathologic" regions in wash-in, peak enhancement intensity and integrated area under the curve are significantly higher than those of "non-affected" regions, irrespective of reference imaging hallmark (p < 0.05). No significant perfusion differences were found between "pathologic" regions with and without osteolysis (p = 0.180). ROC analysis showed fair diagnostic performance of DCE-MRI parameters for identification of MRONJ (AUC 0.626-0.727). CONCLUSIONS: DCE bone perfusion parameters are significantly increased in MRONJ compared to non-affected regions, irrespective of osteolysis. Due to certain overlap DCE-MRI bone perfusion cannot serve as full surrogate for UTE bone imaging but may enhance reader confidence