Publications by authors named "Abbas Agaimy"

474 Publications

Pleomorphic adenoma of the parotid gland presenting as extensively ossified lesion with bone infiltration: a case report.

Braz J Otorhinolaryngol 2021 Nov 4. Epub 2021 Nov 4.

Department of Otolaryngology, Head and Neck Surgery, University Hospital Augsburg, Germany.

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http://dx.doi.org/10.1016/j.bjorl.2021.07.014DOI Listing
November 2021

Renal cell tumor with sex-cord/gonadoblastoma-like features: analysis of 6 cases.

Virchows Arch 2021 Nov 13. Epub 2021 Nov 13.

Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Alej Svobody 80, 304 60, Pilsen, Czech Republic.

Renal tumors are one of the most diverse groups of tumors in pathology. Many emerging and important entities have been described recently. Here, we describe a series of renal tumors occurring in adult patients, with distinct histologic features, and with a striking resemblance to gonadal sex cord-stromal tumors. Patients were three males and three females aged 39-82 years; tumor size ranged from 0.9 to 3.6 cm. Five tumors were organ-confined, while one case had a focal perinephric invasion. No aggressive behavior was noted. Microscopically, all the tumors were composed of loose or compact tubular structures with elongated or angulated shapes. The tumor cells were cylindrical or cuboidal, with pale eosinophilic cytoplasm, irregular nuclear membranes, and ISUP/WHO grade 2-3 nuclei. The stroma showed focal or prominent collagen deposition with prominent basement membrane-like material. In all cases, the tumor cells were positive for PAX8, CD10, and vimentin and retained positivity for FH and SDHB. Cathepsin K and AMACR were variably positive. Tumors were negative for HMB45, Melan A, TFE3, SF1, inhibin, calretinin, ER, PR, CD117, OCT3/4, SALL4, ALK, and WT1. Molecular studies showed no abnormalities in TFEB, TFE3, or FH genes. In 3/4 tested cases, mutation of the NF2 gene was present. In all the tested male cases, loss of the Y chromosome was found. In the relatively short follow-up, these tumors appear to have indolent behavior. This study expands the clinicopathologic diversity of renal cell tumors by describing a series of potentially novel tumors morphologically resembling gonadal sex-stromal tumors, with negativity for sex cord-stromal markers. Potential relationship to recently described biphasic hyalinizing psammomatous renal cell carcinoma is discussed.
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http://dx.doi.org/10.1007/s00428-021-03235-xDOI Listing
November 2021

[Erratum to: Eosinophilic, solid, and cystic renal cell carcinoma (ESC-RCC)].

Pathologe 2021 Oct 25. Epub 2021 Oct 25.

Institut für Pathologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstraße 8-10, 91054, Erlangen, Deutschland.

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http://dx.doi.org/10.1007/s00292-021-01014-8DOI Listing
October 2021

Long-Term Follow-Up of Patients Receiving Neoadjuvant Treatment Modalties for Soft Tissue Sarcomas of the Extremities.

Cancers (Basel) 2021 Oct 19;13(20). Epub 2021 Oct 19.

Department of Surgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.

Background: Neoadjuvant treatment modalities in soft tissue sarcoma (STS) of the extremities have become more popular in recent years, but because of the rarity and heterogeneity of STS, there are yet few studies on the long-term impact of neoadjuvant treatment modalities, especially in terms of neoadjuvant radiochemotherapy.

Methods: The study enrolled 136 patients with primary STS of the extremities who underwent surgery with curative intent or neoadjuvant therapy, followed by surgery in a 15-year period. Neoadjuvant treatment consisted of radiotherapy (RT) with 60 Gy and in most cases simultaneous chemotherapy (CTx) with ifosfamide (1.5 g/m/d, d1-5, q28) and doxorubicine (50 mg/m/d, d3, q28). We investigated the clinical, (post)-operative and histopathological data and the oncological follow-up as well. The median follow-up period was 82 months (range 6-202).

Results: A total of 136 patients (M:F = 73:63) with a mean age of 62 years (range; 21-93) was observed. Seventy-four patients (54.4%) received neoadjuvant therapy (NT), 62 patients (45.6%) received primary surgery (PS). When receiving NT, patients with high-risk STS had a lower risk to develop distant metastasis ( = 0.025). Age, histological type, tumor size and surgical margins (R0 vs. R1) had no influence on any survival rates. There was an association between NT and the occurrence of postoperative complications ( = 0.001). The 5-year local recurrence free survival (LRFS), metastasis free survival (MFS), disease free survival (DFS) and overall survival (OS) rate of the whole cohort was 89.9%, 77.0%, 70.6% and 72.6%; whereas the 5-year LRFS, MFS, DFS and OS rate was 90.5%, 67.2%, 64.1% and 62.8% for the NT group and 89.5%, 88.3%. 78.4% and 83.8% for the PS group.

Conclusions: Multimodal treatment strategies in patients with STS of extremities lead to excellent oncological outcomes. Patients with high-risk STS had a significantly better MFS when receiving NT than patients with low-risk STS. NT was associated with a higher probability of postoperative but well-manageable complications.
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http://dx.doi.org/10.3390/cancers13205244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534061PMC
October 2021

[SMARCB1(INI1)-deficient renal cell carcinoma: medullary and beyond : Evolving concepts].

Pathologe 2021 Nov 5;42(6):571-577. Epub 2021 Oct 5.

Institut für Pathologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstraße 8-10, 91054, Erlangen, Deutschland.

During the last decades, the SWI/SNF chromatin-remodeling complex has received enormous recognition as a major player in the molecular pathogenesis of diverse neoplasms. Accordingly, SWI/SNF defects affecting different subunits of the complex became defining genetic features in the nosology of different neoplastic entities. In the kidney, loss of SMARCB1(INI1) as a major component of the SWI/SNF complex has emerged as the defining genetic marker for renal medullary carcinoma and pediatric malignant rhabdoid tumor. Diagnosis of these two rare entities is based on a set of defined demographic, clinicopathological, immunophenotypic, and genetic (SMARCB1 loss) criteria. Moreover, the sickle cell trait is considered a prerequisite for renal medullary carcinoma. Current knowledge illustrates that SMARCB1 loss is encountered in three major tumor categories in the kidney: (1) histologically defined neoplasms that are primarily driven by de novo SMARCB1 loss (renal medullary carcinoma and malignant rhabdoid tumor); (2) SMRACB1-deficient renal cell carcinoma (RCC) with variable non-specific histology ranging from collecting duct-like, papillary high-grade (papillary type 2), or medullary-like (lacking sickle cell trait), to fully undifferentiated; and (3) biphasic (dedifferentiated) RCC showing a variable SMARCB1-deficient undifferentiated component. The latter variant most frequently originates from pre-existing clear cell RCC but may rarely superimpose on papillary or chromophobe RCC. This review summarizes the major defining features of the emerging SMARCB1-deficient renal neoplasms. All SMARCB1-deficient carcinomas have a poor prognosis in common. Therefore, exact diagnosis of these tumors is a prerequisite for studies investigating new therapies.
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http://dx.doi.org/10.1007/s00292-021-00985-yDOI Listing
November 2021

Pleomorphic (giant cell) carcinoma revisited: A historical perspective and conceptual reappraisal.

Authors:
Abbas Agaimy

Semin Diagn Pathol 2021 Nov 20;38(6):187-192. Epub 2021 Sep 20.

Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital, Erlangen, Germany. Electronic address:

The term pleomorphic "giant cell" carcinoma was coined by Sommers and Meissner in 1954 for a pancreatic carcinoma variant showing a "sarcoma-like transformation" and characterized by an admixture of undifferentiated cells with striking variation in size and shape. Based on the predominant cell type, four patterns were recognized: spindle cell (sarcomatoid), pleomorphic "giant cell", osteoclastic giant cell-rich, and anaplastic round cell. These four basic patterns frequently coexisted within same tumor, albeit to a significantly variable extent. Follow-up series further characterized the entity, expanded its topographic distribution to include almost all organ systems, and illustrated its morphological and phenotypic homology among different organs. Although resemblance of the neoplastic cells to rhabdomyoblasts was already pointed out by Stout in 1958, the term "rhabdoid" (introduced in 1978 for specific kidney tumors) was not used for carcinomas until 1993. Review of the old and recent literature indicates pleomorphic "giant cell" carcinoma is not an entity but a morphological pattern in the spectrum of undifferentiated (anaplastic) and sarcomatoid carcinoma that can originate in any organ, either in a pure form or as a dedifferentiated carcinoma component. These tumors fall into two major categories: a monomorphic (variable admixture of small or larger "gemistocyte-like" rhabdoid cells and epithelioid cells) and a pleomorphic (bizarre large polygonal, spindled, or multinucleated malignant cells) subtype. The few available genetic studies suggest close association of the monomorphic type with SWI/SNF pathway defects, while bizarre-looking pleomorphic tumors usually harbor complex and heterogeneous genetic alterations. Most tumors dominated by the pleomorphic "giant cell" pattern are extremely aggressive, resulting in death, soon after diagnosis, irrespective of treatment modalities. This review gives an historical account on the evolution of the pleomorphic "giant cell" carcinoma concept with special reference to their relationship to SWI/SNF complex alterations.
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http://dx.doi.org/10.1053/j.semdp.2021.09.003DOI Listing
November 2021

Undifferentiated and dedifferentiated urological carcinomas: lessons learned from the recent developments.

Semin Diagn Pathol 2021 Nov 20;38(6):152-162. Epub 2021 Sep 20.

Department of Pathology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.

Loss of the morphological and immunophenotypic characteristics of a neoplasm is a well-known phenomenon in surgical pathology and occurs across different tumor types in almost all organs. This process may be either partial, characterized by transition from well differentiated to undifferentiated tumor component (=dedifferentiated carcinomas) or complete (=undifferentiated carcinomas). Diagnosis of undifferentiated carcinoma is significantly influenced by the extent of sampling. Although the concept of undifferentiated and dedifferentiated carcinoma has been well established for other organs (e.g. endometrium), it still has not been fully defined for urological carcinomas. Accordingly, undifferentiated/ dedifferentiated genitourinary carcinomas are typically lumped into the spectrum of poorly differentiated, sarcomatoid, or unclassified (NOS) carcinomas. In the kidney, dedifferentiation occurs across all subtypes of renal cell carcinoma (RCC), but certain genetically defined RCC types (SDH-, FH- and PBRM1- deficient RCC) seem to have inherent tendency to dedifferentiate. Histologically, the undifferentiated component displays variable combination of four patterns: spindle cells, pleomorphic giant cells, rhabdoid cells, and undifferentiated monomorphic cells with/without prominent osteoclastic giant cells. Any of these may occasionally be associated with heterologous mesenchymal component/s. Their immunophenotype is often simple with expression of vimentin and variably pankeratin or EMA. Precise subtyping of undifferentiated (urothelial versus RCC and the exact underlying RCC subtype) is best done by thorough sampling supplemented as necessary by immunohistochemistry (e.g. FH, SDHB, ALK) and/ or molecular studies. This review discusses the morphological and molecular genetic spectrum and the recent develoments on the topic of dedifferentiated and undifferentiated genitourinary carcinomas.
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http://dx.doi.org/10.1053/j.semdp.2021.09.004DOI Listing
November 2021

The challenge of undifferentiated malignancies: Phenotype versus genotype! What matters most?

Authors:
Abbas Agaimy

Semin Diagn Pathol 2021 Nov 20;38(6):117-118. Epub 2021 Sep 20.

Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital, Krankenhausstrasse 8-10, 91054 Erlangen, Germany. Electronic address:

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http://dx.doi.org/10.1053/j.semdp.2021.09.002DOI Listing
November 2021

[Eosinophilic, solid, and cystic renal cell carcinoma (ESC-RCC)].

Pathologe 2021 Nov 22;42(6):565-570. Epub 2021 Sep 22.

Institut für Pathologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstraße 8-10, 91054, Erlangen, Deutschland.

Despite its descriptive name, eosinophilic, solid, and cystic renal cell carcinoma (ESC-RCC) represents a distinctive epithelial renal tumor entity defined by characteristic clinicopathological and molecular features. ESC-RCC occurs predominantly in women and is characterized in the majority of cases by sporadic (somatic) TSC mutations. A small subset of cases, however, affects patients with TSC germline mutations (tuberous sclerosis syndrome). TSC mutations have therefore been shown to be pathogenetic in this type of tumor. Most tumors present as small (pT1) well circumscribed but not encapsulated lesions with variable macrocystic spaces on their cut surface. Immunohistochemically, their CD117-/CK7-/CK20+ profile is characteristic. Although the tumor cell nuclei of the ESC-RCC occasionally correspond to ISUP/WHO grade 2-3, these tumors are essentially indolent with aggressive cases being only rarely observed. Single case reports have documented effective treatment of aggressive cases with mTOR inhibitors. ESC-RCC needs to be distinguished from a variety of eosinophilic RCC types with secondary cystic changes including cystic SDH-deficient RCC, the recently proposed eosinophilic vacuolated tumor (EVT; also mTOR-related), oncocytoma, and low-grade oncocytic tumor (LOT). The generally indolent behavior and frequent TSC/mTOR alterations in ESC-RCC, EVT, and some LOTs raise the question of whether these lesions represent independent tumor entities or are merely morphological variants on the spectrum of eosinophilic low-grade TSC/mTOR-related neoplasms.
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http://dx.doi.org/10.1007/s00292-021-00998-7DOI Listing
November 2021

Eosinophilic vacuolated tumor (EVT) of kidney demonstrates sporadic TSC/MTOR mutations: next-generation sequencing multi-institutional study of 19 cases.

Mod Pathol 2021 Sep 14. Epub 2021 Sep 14.

Department of Pathology, University of Toronto, Toronto, ON, Canada.

A distinct renal tumor has recently been described as "high-grade oncocytic renal tumor" and "sporadic renal cell carcinoma with eosinophilic and vacuolated cytoplasm". The Genitourinary Pathology Society (GUPS) consensus proposed a unifying name "eosinophilic vacuolated tumor" (EVT) for this emerging entity. In this multi-institutional study, we evaluated 19 EVTs, particularly their molecular features and mutation profile, using next-generation sequencing. All cases were sporadic and none of the patients had a tuberous sclerosis complex. There were 8 men and 11 women, with a mean age of 47 years (median 50; range 15-72 years). Average tumor size was 4.3 cm (median 3.8 cm; range 1.5-11.5 cm). All patients with available follow-up data (18/19) were alive and without evidence of disease recurrence or progression during the follow-up, ranging from 12 to 198 months (mean 56.3, median 41.5 months). The tumors were well circumscribed, but lacked a well-formed capsule, had nested to solid growth, focal tubular architecture, and showed ubiquitous, large intracytoplasmic vacuoles, round to oval nuclei, and prominent nucleoli. Immunohistochemically, cathepsin K, CD117, CD10, and antimitochondrial antigen were expressed in all cases. Other positive stains included: PAX8, AE1/AE3 and CK18. CK7 was typically restricted only to rare scattered cells. Vimentin, HMB45, melan-A, and TFE3 were negative in all cases. All tumors showed retained SDHB. All cases (19/19) showed non-overlapping mutations of the mTOR pathway genes: TSC1 (4), TSC2 (7), and MTOR (8); one case with MTOR mutation showed a coexistent RICTOR missense mutation. Low mutational rates were found in all samples (ranged from 0 to 6 mutations/Mbp). Microsatellite instability and copy number variations were not found in any of the 17 analyzable cases. EVT represents an emerging renal entity that shows a characteristic and readily identifiable morphology, consistent immunohistochemical profile, indolent behavior, and mutations in either TSC1, TSC2, or MTOR genes.
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http://dx.doi.org/10.1038/s41379-021-00923-6DOI Listing
September 2021

Sclerosing Polycystic Adenoma of Salivary Glands: A Novel Neoplasm Characterized by PI3K-AKT Pathway Alterations-New Insights Into a Challenging Entity.

Am J Surg Pathol 2021 Sep 13. Epub 2021 Sep 13.

Department of Pathology, Charles University, Faculty of Medicine in Plzen Bioptic Laboratory Ltd Molecular and Genetic Laboratory, Bioptic Laboratory Ltd, Plzen The Fingerland Department of Pathology, Charles University, Faculty of Medicine and University Hospital Hradec Kralove, Hradec Králové Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine in Prague, Prague, Charles University and Motol University Hospital, Prague, Czech Republic Department of Histopathology, Division of Clinical Medicine, University of Surrey, Royal Surrey County Hospital, Guildford, Surrey, UK Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Comprehensive Cancer Center (CCC) Erlangen-EMN, Erlangen, Germany Department of Pathology, CHU Gui de Chauliac, Montpellier, France Department of Pathology, National University Health System, Singapore, Singapore Department of Pathology, Research Institute GROW, Maastricht University Medical Center, Maastricht, The Netherlands Department of Anatomic Histopathology and Cytogenetics, Department of Laboratory Medicine, Niguarda Cancer Center, Milan, Italy Medical Laboratory CSD, Kyiv, Ukraine Institute of Biomedicine, Pathology, University of Turku, and Turku University Hospital, Turku, Finland.

Sclerosing polycystic adenoma (SPA) is a rare salivary gland neoplasm originally thought to represent a non-neoplastic lesion. Recently we have encountered an index case of apocrine intraductal carcinoma of parotid gland of 62-year-old man with invasive salivary duct carcinoma component arising from SPA, a combination of tumor entities that has never been published so far. Here, we further explore the nature of SPA by evaluating 36 cases that were identified from the authors' consultation files. The patients were 25 females and 11 males aged 11 to 79 years (mean, 47.8 y). All tumors originated from the parotid gland. Their size ranged from 11 to 70 mm (mean, 28 mm). Histologically, all cases revealed characteristic features of SPA, such as lobulated well-circumscribed growth, focal hyalinized sclerosis, presence of large acinar cells with abundant brightly eosinophilic intracytoplasmic granules, and ductal components with variable cytomorphologic characteristics, including foamy, vacuolated, apocrine, mucous, clear/ballooned, squamous, columnar and oncocyte-like cells. In all cases, there were foci of intraluminal solid and cribriform intercalated duct-like epithelial proliferations with variable dysplasia which were positive for S100 protein and SOX10, and fully enveloped by an intact layer of myoepithelial cells. In addition, 14/36 cases (39%) had focal intraductal cribriform and micropapillary apocrine-type dysplastic epithelial structures composed of cells positive for androgen receptors and negative for S100/SOX10. The intraductal proliferations of both types showed focal mild to severe dysplasia in 17 cases (17/36; 47%). Two cases showed overt malignant morphology ranging from high-grade intraductal carcinoma to invasive carcinoma with an apocrine ductal phenotype. Next generation sequencing using ArcherDX panel targeting RNA of 36 pan-cancer-related genes and/or a TruSight Oncology 170/500 Kit targeting a selection of DNA from 523 genes and RNA from 55 genes was performed. Tumor tissue was available for molecular analysis in 11 cases, and 9 (9/11; 82%) of them harbored genetic alterations in the PI3K pathway. Targeted sequencing revealed HRAS mutations c.37G>C, p.(Gly13Arg) (2 cases) and c.182A>G, p.(Gln61Arg) (2 cases), and PIK3CA mutations c.3140A>G, p.(His1047Arg) (3 cases), c.1633G>A, p.(Glu545Lys) (1 case), and c.1624G>A, p.(Glu542Lys) (1 case). Moreover, mutations in AKT1 c.49G>A, p.(Glu17Lys) and c.51dup, p.(Tyr18ValfsTer15); c.49_50delinsAG, p.(Glu17Arg) (as a double hit) were found (2 cases). In addition, germinal and somatic mutation of PTEN c.1003C>T, p.(Arg335Ter); c.445C>T, p.(Gln149Ter), respectively, were detected. Gene fusions were absent in all cases. These prevalent molecular alterations converging on one major cancer-related pathway support the notion that SPA is a true neoplasm with a significant potential to develop intraluminal epithelial proliferation with apocrine and/or intercalated duct-like phenotype. The name SPA more correctly reflects the true neoplastic nature of this enigmatic lesion.
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http://dx.doi.org/10.1097/PAS.0000000000001807DOI Listing
September 2021

IgG4-related fasciitis.

Rheumatology (Oxford) 2021 Aug 30. Epub 2021 Aug 30.

Department of Internal Medicine 3 - Rheumatology and Immunology, University Hospital of Erlangen-Nuremberg, Erlangen, Germany.

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http://dx.doi.org/10.1093/rheumatology/keab669DOI Listing
August 2021

High-grade salivary gland cancer: is surgery followed by radiotherapy an adequate treatment to reach tumor control? Results from a tertiary referral centre focussing on incidence and management of distant metastases.

Eur Arch Otorhinolaryngol 2021 Aug 26. Epub 2021 Aug 26.

Department of Radiation Oncology, University Hospital of Erlangen, Friedrich -Alexander-University Erlangen-Nürnberg (FAU), Universitätsstraße 27, 91054, Erlangen, Germany.

Purpose: Salivary Gland cancer (SGC) is a rare and heterogenous group of tumors. Standard therapeutic options achieve high local but poor distant control rates, especially in high-grade SGC. The aim of this monocentric study was to evaluate patterns of recurrence and its treatment options (local ablative vs. systemic) in a homogenously treated patient population with high-grade SGC after surgery and radio(chemo)therapy.

Methods: Monocentric, retrospective study of patients with newly diagnosed high-grade salivary gland cancer. We retrospectively reviewed clinical reports from 69 patients with high-grade salivary gland cancer in a single-center audit. Survival rates were calculated using the Kaplan-Meier method and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox regression analysis).

Results: The median time of follow-up was 31 months. After 5 years, the cumulative overall survival was 65.2%, cumulative incidence of local recurrence was 7.2%, whereas the cumulative incidence of distant metastases was 43.5% after 5 years. 30 of 69 patients developed distant metastases during the time of follow-up, especially patients with adenoid cystic carcinoma, salivary duct carcinoma, adenocarcinoma NOS and acinic cell carcinoma with high-grade transformation. The most common type of therapy therefore was chemotherapy (50%). 85.7% of patients with local ablative therapy of distant metastases show disease progression during follow-up afterwards.

Conclusion: With surgery and radio-chemotherapy, a high rate of loco-regional control is reached, but over 40% of patients develop distant metastases in the further follow-up which usually present a diffuse pattern involving in a diffuse metastases. Therefore, in the future, intensified interdisciplinary combination therapies even in the first-line treatment in certain subtypes of high-grade SGC should be investigated.
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http://dx.doi.org/10.1007/s00405-021-07024-9DOI Listing
August 2021

Quantification of Translocation-Specific ctDNA Provides an Integrating Parameter for Early Assessment of Treatment Response and Risk Stratification in Ewing Sarcoma.

Clin Cancer Res 2021 Nov 23;27(21):5922-5930. Epub 2021 Aug 23.

Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany.

Purpose: We evaluated the predictive and prognostic value of circulating tumor DNA (ctDNA) in patients with Ewing sarcoma (EWS) treated in the EWING2008 trial.

Experimental Design: Plasma samples from 102 patients with EWS enrolled in the EWING2008 trial were obtained before and during induction chemotherapy. Genomic fusion sequence spanning primers and probes were used for highly specific and sensitive quantification of the levels of ctDNA by digital droplet PCR. ctDNA levels were correlated to established clinical risk factors and outcome parameters.

Results: Pretreatment ctDNA copy numbers were correlated with event-free and overall survival. The reduction in ctDNA levels below the detection limit was observed in most cases after only two blocks of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) induction chemotherapy. The persistence of ctDNA after two VIDE blocks was a strong predictor of poor outcomes. ctDNA levels correlated well with most established clinical risk factors; an inverse correlation was found only for the histologic response to induction therapy. ctDNA levels did not provide simple representations of tumor volume, but integrated information from various tumor characteristics represented an independent EWS tumor marker with predictive and prognostic value.

Conclusions: ctDNA copy number in the plasma of patients with EWS is a quantifiable parameter for early risk stratification and can be used as a dynamic noninvasive biomarker for early prediction of treatment response and outcome of patients.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1324DOI Listing
November 2021

Primary lung carcinoma in children and adolescents - Clinical characteristics and outcome of 12 cases from the German registry for rare paediatric tumours (STEP).

Lung Cancer 2021 10 11;160:66-72. Epub 2021 Aug 11.

Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tuebingen, Germany. Electronic address:

Objectives: Primary lung carcinomas are very rare paediatric tumours with an incidence of < 2/1.000.000 per year. They are clinically and histologically heterogeneous, and there are no therapeutic guidelines for this age group. Therefore, they represent a challenge for treating physicians. This analysis was performed to expand knowledge on characteristics, treatment and prognosis of primary lung carcinoma in paediatric patients.

Material And Methods: Between 2009 and 2019, twelve children and adolescents with lung carcinoma were identified in the prospective German registry for rare paediatric tumours (STEP). Data were analysed for histopathological entities, symptoms, diagnostics, therapy, clinical course and outcome.

Results: Mucoepidermoid carcinoma (MEC) was the most frequent entity (n = 7), followed by adenocarcinoma (n = 2), squamous cell carcinoma (SCC; n = 2) and adenosquamous carcinoma (n = 1). Patients presented with non-specific symptoms and often, they were initially mistreated for airway infections. Patients with MEC showed no metastases and were successfully treated with complete resection. Patients with adenocarcinoma and SCC were older than 16 years of age at diagnosis. While patients with SCC presented with distant metastases and died within one year after diagnosis, those with adenocarcinoma and adenosquamous carcinoma achieved complete remission after multimodal treatment.

Conclusions: Presenting symptoms of lung carcinomas are unspecific and therefore, diagnostic evaluation and treatment are difficult. In the absence of carcinogen exposure, etiology seems to differ from adult lung carcinoma. Children diagnosed with MEC face a favourable outcome. In contrast, patients with prognostically unfavourable adenocarcinoma and SCC might benefit from molecular profiling and targeted therapies. International collaboration for the establishment of treatment protocols adjusted for distinct features of primary lung carcinoma in childhood is essential.
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http://dx.doi.org/10.1016/j.lungcan.2021.08.004DOI Listing
October 2021

Rapidly fatal SMARCA4-deficient undifferentiated sarcoma originating from hybrid hemosiderotic fibrolipomatous tumor/pleomorphic hyalinizing angiectatic tumor of the foot.

Virchows Arch 2021 Aug 14. Epub 2021 Aug 14.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts and hemosiderotic fibrolipomatous tumor (HFLT) are two rare low-grade locally recurring neoplasms with predilection for the foot/ankle. Recent studies support a close link between the two entities, and origin of PHAT from HFLT and occurrence of hybrid HFLT/PHAT have been documented. Both lesions often harbor TGFBR3 or MGEA5 rearrangements. Rare sarcomas originating from HFLT/PHAT have been reported, typically resembling myxofibrosarcoma or myxoinflammatory fibroblastic sarcoma. We describe a novel SMARCA4-deficient undifferentiated sarcoma with rhabdoid features originating from hybrid HFLT/PHAT in the foot of a 54-year-old male. The tumor pursued a highly aggressive course with rapid regrowth after resection and multiple metastases resulting in patient's death within 5 months, despite systemic chemotherapy. Immunohistochemistry revealed SMARCA4 loss in the undifferentiated sarcoma, but not in the HFLT/PHAT. Molecular testing confirmed TGFBR3/MGEA5 rearrangements. This report expands the phenotypes of sarcomas developing from pre-existing PHAT/HFLT.
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http://dx.doi.org/10.1007/s00428-021-03167-6DOI Listing
August 2021

Comprehensive Immunohistochemical Study of the SWI/SNF Complex Expression Status in Gastric Cancer Reveals an Adverse Prognosis of SWI/SNF Deficiency in Genomically Stable Gastric Carcinomas.

Cancers (Basel) 2021 Aug 2;13(15). Epub 2021 Aug 2.

Institute of General Pathology and Molecular Diagnostics, University Hospital Augsburg, 86156 Augsburg, Germany.

The SWI/SNF complex has important functions in the mobilization of nucleosomes and consequently influences gene expression. Numerous studies have demonstrated that mutations or deficiency of one or more subunits can have an oncogenic effect and influence the development, progression, and eventual therapy resistance of tumor diseases. Genes encoding subunits of the SWI/SNF complex are mutated in approximately 20% of all human tumors. This study aimed to investigate the frequency, association with clinicopathological characteristics, and prognosis of immunohistochemical expression of proteins of the SWI/SNF complexes, SMARCA2, SMARCA4 SMARCB1, ARID1A, ARID1B, and PBRM1 in 477 adenocarcinomas of the stomach and gastroesophageal junction. Additionally, the tumors were classified immunohistochemically in analogy to The Cancer Genome Atlas (TCGA) classification. Overall, 32% of cases demonstrated aberrant expression of the SWI/SNF complex. Complete loss of SMARCA4 was detected in three cases (0.6%) and was associated with adverse clinical characteristics. SWI/SNF aberration emerged as an independent negative prognostic factor for overall survival in genomically stable patients in analogy to TCGA. In conclusion, determination of SWI/SNF status could be suggested in routine diagnostics in genomically stable tumors to identify patients who might benefit from new therapeutic options.
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http://dx.doi.org/10.3390/cancers13153894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345509PMC
August 2021

Mesenchymal/non-epithelial mimickers of neuroendocrine neoplasms with a focus on fusion gene-associated and SWI/SNF-deficient tumors.

Virchows Arch 2021 Aug 5. Epub 2021 Aug 5.

Department of Pathology, Technical University Munich, Trogerstr. 18, 81675, Munich, Germany.

Mimickers of neuroendocrine neoplasms (NEN) include a number of important pitfall tumors. Here, we describe our experience with mesenchymal mimics of NENs to illustrate their spectrum and draw the attention particularly to a group of mesenchymal/non-epithelial neoplasms (MN) that combine epithelioid histology with neuroendocrine (NE-) features and peculiar genetic abnormalities. In a consultation series of 4498 cases collected between 2009 and 2021, 2099 neoplasms expressing synaptophysin and/or chromograninA were reviewed and analyzed. A total of 364 (18%) were diagnosed as non-NENs, while the remaining tumors were NEN. The group of mesenchymal/non-epithelial neoplasms with NE-features (MN-NE) included 31/364 (8%) cases. These mostly malignant neoplasms showed an epithelioid morphology. While all but one tumor expressed synaptophysin, mostly patchy, only 10/29 (34%) co-expressed chromograninA. A total of 13/31 (42%) of the MN-NE showed EWSR1-related gene fusions (6 Ewing sarcomas, 5 clear cell sarcomas, and 1 desmoplastic small round cell tumor, 1 neoplasm with FUS-CREM gene fusion) and 7 (23%) were SWI/SNF (SMARCB1 or SMARCA4)-deficient neoplasms. The remaining MN-NE included synovial sarcoma, sclerosing epithelioid mesenchymal neoplasm, melanoma, alveolar soft part sarcoma, solitary fibrous tumor, and chordoma. A total of 27/31 MN-NE were from the last 8 years, and 6 of them were located in the pancreas. Eleven MN-NE were initially diagnosed as neuroendocrine carcinomas (NECs). MN-NE with epithelioid features play an increasing role as mimickers of NECs. They mostly belong to tumors with gene fusions involving the EWSR1 gene, or with SWI/SNF complex deficiency. Synaptophysin expression is mostly patchy and chromograninA expression is infrequent in MN-NE of this series and data extracted from literature.
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http://dx.doi.org/10.1007/s00428-021-03156-9DOI Listing
August 2021

HMGA2-WIF1 Rearrangements Characterize a Distinctive Subset of Salivary Pleomorphic Adenomas With Prominent Trabecular (Canalicular Adenoma-like) Morphology.

Am J Surg Pathol 2021 Jul 29. Epub 2021 Jul 29.

Institute of Pathology, Comprehensive Cancer Center (CCC) Erlangen-EMN Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital Erlangen DERMPATH Muenchen Institute of Pathology, Ludwig Maximilians University, Munich, Germany Department of Pathology, Charles University, Faculty of Medicine in Plzen Bioptic Laboratory Ltd, Plzen, Czech Republic Department of Pathology, University Hospital Montpellier, Montpellier, France.

Most of salivary gland neoplasms (benign and malignant) are characterized by recurrent gene fusions. Pleomorphic adenoma (PA), the most frequent salivary gland tumor, is driven by chromosomal rearrangements involving PLAG1 mapped to 8q12 and HMGA2 mapped to 12q13-15 in most cases. Multiple fusion partners have been identified including CTNNB1, FGFR1, LIFR, CHCHD7 and TCEA for PLAG1 fusions and NFIB, WIF1 and FHIT for HMGA2 fusions. To date, no data exist on the morphology of the few reported HMGA2-WIF1-rearranged PAs. We present 28 major salivary gland adenomas displaying distinctive trabecular and canalicular morphology associated with recurrent genotype. Patients were 15 females and 13 males aged 43 to 87 (median: 65). All tumors originated from the parotid. Their size range was 1 to 4 cm (mean: 2.3). Histologically, all tumors showed elongated or columnar cells arranged into bilayered to multilayered communicating and branching strands and trabeculae in a manner similar to canalicular adenoma of minor salivary glands or trabecular myoepithelioma with variable solid confluent intercalated duct-like areas. Fifteen tumors were exclusively canalicular/trabecular while 13 had intermingled or well-demarcated conventional (chondromyxoid) PA component comprising 5 to >50% of the tumor. The monomorphic areas expressed uniformly CK7 (28/28), vimentin (21/21), S100 (24/24), SOX10 (16/17) and variably p63 (8/21) and mammaglobin (6/16) but were negative with p40 (0/24), smooth muscle actin (0/24) and MUC4 (0/16). Targeted RNA sequencing revealed HMGA2 fusions in 14/16 (87%) assessable cases. Fusion partner was WIF1 (12), RPSAP52 (1) and HELB (1). Separate testing of the 2 components in 1 hybrid tumor showed same HMGA2/WIF1 fusion. HMGA2 immunohistochemistry was homogeneously positive in all cases including the 2 fusion-negative cases. A control cohort of 12 genuine canalicular adenomas revealed no HMGA2 fusions (0/4) and lacked HMGA2 immunoreactivity (0/12). This study highlights a distinctive variant in the spectrum of PA characterized by prominent trabecular and canalicular adenoma-like morphology. Our data confirm that canalicular adenomas in major salivary glands (either monomorphic or part of hybrid tumors) are distinct from canalicular adenoma of minor salivary glands. Their uniform genotype irrespective of presence or absence of a conventional PA component argues for classifying those tumors lacking a conventional PA component as "monomorphic variants of PA" rather than canalicular/basal cell adenomas, intercalated duct adenoma, trabecular myoepithelioma or true hybrid tumors.
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http://dx.doi.org/10.1097/PAS.0000000000001783DOI Listing
July 2021

DICER1-Mutated Botryoid Fibroepithelial Polyp of the Parotid Duct: Report of the First Case.

Head Neck Pathol 2021 Jul 19. Epub 2021 Jul 19.

Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), University Hospital Erlangen (UKER), Krankenhausstrasse 8-10, 91054, Erlangen, Germany.

DICER1, a member of the ribonuclease III family, is involved in the biogenesis of microRNAs and, hence, it influences gene expression regulation. DICER1 germline (associated with the inherited DICER1 syndrome) or somatic mutations have been linked to tumorigenesis in histogenetically diverse benign and malignant neoplasms in different organs including pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma, nasal chondromesenchymal hamartoma, poorly differentiated thyroid carcinoma, thyroblastoma, intracranial sarcoma and gonadal Sertoli-Leydig cell tumors in addition to others. Moreover, rare botryoid (giant) fibroepithelial polyps may harbor this mutation. Herein, we describe the first reported case of a DICER1-mutated botryoid fibroepithelial polyp occurring within the parotid duct of a 65-year-old female who has no other features or family history of the DICER1 syndrome. Based on its distinctive morphology, we tested this lesion specifically for DICER1 mutations and confirmed the presence of a pathogenic DICER1 variant with a low allele frequency, consistent with a somatic mutation.
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http://dx.doi.org/10.1007/s12105-021-01364-yDOI Listing
July 2021

PRRX1-NCOA1-rearranged fibroblastic tumour: a clinicopathological, immunohistochemical and molecular genetic study of six cases of a potentially under-recognised, distinctive mesenchymal tumour.

Histopathology 2021 Dec 3;79(6):997-1003. Epub 2021 Sep 3.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.

Aims: PRRX1-NCOA1-rearranged fibroblastic tumour is a recently described, rare mesenchymal tumour. Only four cases have been previously reported. The aim of this article is to report six additional cases of this unusual mesenchymal neoplasm, with an emphasis on its differential diagnosis.

Methods And Results: The six cases were from three females and three males (age, 20-49 years; median, 42 years). Three tumours were located on the abdominal wall; two from the shoulder/axillary areas, and one on the lateral hip. All presented as slow-growing subcutaneous nodules, ranging from 26 to 55 mm (median, 40 mm). The tumours consisted of circumscribed, variably cellular nodules composed of relatively bland plump spindled to epithelioid cells arranged singly, in cords, and occasionally in nests, embedded in hyalinised and collagenous stroma. Small hypocellular myxoid zones with ropey collagen fibres were present, as were irregularly dilated, gaping, crescent-shaped or staghorn-like thin-walled vessels, best appreciated at the periphery. Immunohistochemistry for CD34, S100, MUC4 and STAT6 was consistently negative. RNA-sequencing revealed PRRX1-NCOA1 fusions in all cases. Of the four cases with limited follow-up (1.5-4 months), none recurred following local surgical excision.

Conclusions: The morphological features of PRRX1-NCOA1-rearranged fibroblastic tumour overlap with those of RB1-deficient soft-tissue tumours, solitary fibrous tumour, and low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma. This differential diagnosis can be resolved with a combination of careful morphological study and the application of a panel of immunostains, although molecular genetic study is most definitive. The natural history of PRRX1-NCOA1-rearranged fibroblastic tumour appears to be quite favourable, although longer-term study of a larger number of cases is warranted.
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http://dx.doi.org/10.1111/his.14454DOI Listing
December 2021

IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies: Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome.

Am J Surg Pathol 2021 09;45(9):1190-1204

Departments of Neuropathology.

IDH2 R172 mutations occur in sinonasal undifferentiated carcinoma (SNUC), large-cell neuroendocrine carcinoma (LCNEC), sinonasal adenocarcinomas, and olfactory neuroblastoma (ONB). We performed a clinical, pathologic, and genetic/epigenetic analysis of a large IDH2-mutated sinonasal tumor cohort to explore their distinct features. A total 165 sinonasal/skull base tumors included 40 IDH2 mutants studied by light microscopy, immunohistochemistry, and genome-wide DNA methylation, and 125 IDH2 wild-type tumors used for comparison. Methylation profiles were analyzed by unsupervised hierarchical clustering, t-distributed stochastic neighbor embedding dimensionality reduction and assessed for copy number alterations (CNA). Thirty-nine histologically assessable cases included 25 (64.1%) SNUC, 8 (20.5%) LCNEC, 2 (5.1%) poorly differentiated adenocarcinomas, 1 (2.7%) ONB, and 3 (7.7%) IDH2-mutated tumors with ONB features. All cases were high-grade showing necrosis (82.4%), prominent nucleoli (88.9%), and median 21 mitoses/10 HPFs. AE1/AE3 and/or CAM 5.2 were positive in all and insulinoma-associated protein 1 (INSM1) in 80% cases. All IDH2 mutants formed one distinct group by t-distributed stochastic neighbor embedding dimensionality reduction separating from all IDH2 wild-type tumors. There was no correlation between methylation clusters and histopathologic diagnoses. Recurrent CNA included 1q gain (79.3%), 17p loss (75.9%), and 17q gain (58.6%). No CNA differences were observed between SNUC and LCNEC. IDH2 mutants showed better disease-specific survival than SMARCB1-deficient (P=0.027) and IDH2 wild-type carcinomas overall (P=0.042). IDH2-mutated sinonasal tumors are remarkably homogeneous at the molecular level and distinct from IDH2 wild-type sinonasal malignancies. Biology of IDH2-mutated sinonasal tumors might be primarily defined by their unique molecular fingerprint rather than by their respective histopathologic diagnoses.
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http://dx.doi.org/10.1097/PAS.0000000000001697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373679PMC
September 2021

Diffuse Neuromatosis of Intrahepatic and Extrahepatic Bile Ducts as a Rare Cause of Jaundice.

Visc Med 2021 Jun 30;37(3):226-232. Epub 2020 Sep 30.

Department of Pathology, University Hospital Erlangen, Erlangen, Germany.

Background: Neuroma of the biliary tree is extremely rare with no more than 100 cases reported so far. They mostly present with obstructive jaundice and have been commonly described after surgery or abdominal trauma. Although involvement of the extrahepatic bile duct is far more common, occurrence in the intrahepatic ducts has not so far been reported.

Case Report: We describe 3 cases of diffuse biliary tree neuroma affecting 3 females aged 53-68 years. None had a history of neurofibromatosis type1. All presented with progressive obstructive jaundice with no evidence of gallstones. A history of previous surgery was noted in 2 patients. Initial impression on clinical and imaging examination was highly suspicious for bile duct carcinoma in 2 patients. Histology showed diffuse neuromatous proliferation replacing and thickening the bile duct walls. The third patient had concurrent neuroma and recurrent cholangiocarcinoma causing great clinical confusion as initial biopsy showed only benign neuroma, but CA 19-9 was steadily increasing, necessitating a second biopsy which then confirmed recurrent carcinoma.

Conclusion: This uncommon cause of long-distance bile duct stenosis and progressive jaundice should be included in the differential diagnosis of bile duct neoplasms, in particular when there is a previous surgical history in this abdominal region.
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http://dx.doi.org/10.1159/000510486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237796PMC
June 2021

Misleading Germ Cell Phenotype in Pulmonary NUT Carcinoma Harboring the ZNF532-NUTM1 Fusion.

Am J Surg Pathol 2021 Jul 8. Epub 2021 Jul 8.

Institute of Pathology, University Hospital, Erlangen Department of Cardio-Thoracic Surgery, Heart and Diabetes Center North Rhine Westphalia, Bad Oeynhausen, Nordrhein-Westfalen Clinic for General and Interventional Cardiology/Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany Brigham and Women's Hospital/Harvard Medical School, Boston, MA.

NUT carcinoma (aka NUT midline carcinoma) is a rare, still significantly underrecognized aggressive malignancy. Although historically considered a midline malignancy of children and young adults, NUT carcinoma can originate in almost any body site and in any age group. Beside the classic BRD4-NUTM1 fusion, less common fusion partners include BRD3, NSD3, ZNF532, and ZNF592. Other fusions, including CIC, MGA, MXD4, MXD1, and BCORL1 are associated with sarcomas or cancers of unknown histogenesis. Involvement of the Z4 zinc finger protein (ZNF) family members ZNF532 and ZNF592 is exceedingly rare with only 3 recently reported cases. We herein describe a ZNF532-NUTM1-rearranged NUT carcinoma presenting as a 7.5 cm mass in the left lower lung lobe of a 65-year-old woman. Histology revealed undifferentiated monotonous small round cells with focal epithelioid and rhabdoid elements within a variably myxoid stroma. Immunohistochemistry revealed paucity of keratins and variable p63 combined with extensive CD30 and PLAP expression, leading to initial diagnoses of combined small cell carcinoma, CD30-positive unclassified hematolymphoid malignancy and malignant germ cell neoplasm. Negativity for other more specific germ cell markers justified seeking a fourth opinion, which revealed diffuse expression of the NUT antibody. The diagnosis was then confirmed by fluorescence in situ hybridization. Targeted RNA sequencing revealed the ZNF532-NUTM1 fusion. Screening of 7 NUT carcinomas (5 with BRD4-NUTM1 and 2 with NSD3-NUTM1 fusions) for germ cell markers revealed focal SALL4 reactivity in 3 cases (combined with variable AFP expression in 2), but none expressed CD30 or PLAP. An aberrant germ cell immunophenotype should be considered in NUT carcinoma to avoid misinterpretation as genuine germ cell malignancy as both diseases predominantly affect the young population, frequently involve the mediastinum and can be associated with elevated serum AFP.
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http://dx.doi.org/10.1097/PAS.0000000000001774DOI Listing
July 2021

Intra-abdominal EWSR1/FUS-CREM-rearranged malignant epithelioid neoplasms: two cases of an emerging aggressive entity with emphasis on misleading immunophenotype.

Virchows Arch 2021 Jul 6. Epub 2021 Jul 6.

Institute of Pathology, Technical University Munich, Munich, Germany.

CREB family (CREB1, ATF1, and CREM) gene fusions are defining markers in diverse mesenchymal neoplasms (clear cell sarcoma, angiomatoid fibrous histiocytoma, and others). However, neoplasms harboring EWSR1-CREM/FUS-CREM fusions are rare and poorly characterized. We describe two cases (55-year-old male with 7.5 cm renal mass and 32-year-old female with 5.5 cm mesenteric mass) illustrating their misleading immunophenotypes. Histologically, both showed eosinophilic and focally clear epithelioid cells arranged into sheets, nests, and trabeculae. Immunohistochemistry showed ALK, EMA, and AE1/AE3 immunoreactivity suggesting ALK-rearranged renal cell carcinoma (Case 1) and coexpression of keratin, EMA, synaptophysin, and chromogranin-A, suggesting neuroendocrine neoplasm (Case 2). Targeted RNA sequencing revealed EWSR1-CREM (Case 1) and FUS-CREM (Case 2) fusions. These cases add to the spectrum of CREM fusion-positive intra-abdominal epithelioid neoplasms. Their unusual immunophenotype and unexpected sites represent major pitfalls, underline a wide differential diagnosis, and emphasize the value of molecular testing in correctly diagnosing them.
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http://dx.doi.org/10.1007/s00428-021-03140-3DOI Listing
July 2021

Histopathology of Parotid Pleomorphic Adenomas: A "Pleomorphic Approach" to a Demanding Lesion.

Laryngoscope 2021 Jul 2. Epub 2021 Jul 2.

Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.

Objectives/hypothesis: The aim of this study was to identify potential associations between epidemiologic, morphologic, and histopathologic features in pleomorphic adenomas (PAs) of the parotid gland in order to extract information about the natural course and biologic behavior of these lesions on the basis of a single-center series of 845 cases within a period of 15 years.

Study Design: Retrospective study in a tertiary academic center.

Methods: For this study, an experienced head and neck pathologist critically re-evaluated the histological slides of the pathological specimens of all patients who underwent a parotidectomy for PA of the parotid gland between 2006 and 2020.

Results: A total of 845 cases made up our study sample. Our analysis showed a statistically significant association of the histologic subtype with younger age (P = .001) and maximal diameter (P = .044), with the hypocellular type being encountered more often in younger patients and in smaller lesions. The same subtype was significantly associated with an incomplete capsule (P = .001), pseudopodia (P = .006), and satellite nodules (P = .001). An incomplete capsule was associated with the presence of pseudopodia (P = .001) and satellite nodules (P = .001).

Conclusion: It seems that various histologic subtypes have different capsule-producing properties. Apparently, over the course of time, tumor material builds a finger-like projection still inside the capsule, separates itself from the parenchyma with fibrous tissue still remaining enclosed within the capsule (pseudopodium), slowly penetrates the capsule (incomplete capsule), and leaves the main lesion taking a part of the capsule with it (satellite nodules). Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29726DOI Listing
July 2021
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