Pretreatment tumor sampling and prognostic factors in patients with soft-tissue sarcoma of the head and neck

Correction: DOI10.1007/s00405-021-07205-6 Early AccessDEC 2021Background Insufficient preoperative work-up and consequent intralesional or marginal resection of soft-tissue sarcomas of the head and neck (STSHNs) is common. Methods This retrospective cohort study comprised 63 patients with STSHN treated at the Helsinki University Hospital between 2005 and 2017. We assessed the effect of pretreatment tumor sampling on surgical margin status and need for supplemental surgery, as well as prognostic factors and survival. Results The lack of representative pretreatment biopsy specimen was associated with unfavorable margin status. Primary surgery at a non-academic center was associated with need for supplemental surgery. The 3-year overall survival (OS) was 68%, disease-specific survival (DSS) 71%, and recurrence-free survival (RFS) 61%. Higher tumor grade and primary tumor size over 5 cm were associated with reduced DSS. Conclusions Diagnosis and management of STSHNs should be centralized to experienced academic centers. Decision-making between needle biopsy, open biopsy, or upfront radical surgery depends on tumor location and size.Peer reviewe

Challenging Management of Plexiform Schwannoma and Plexiform Neurofibroma

Plexiform variants of neurofibromas and schwannomas are rare and typically arise in superficial soft tissues in the head and neck region. The treatment of these tumors is challenging and no generally accepted guidelines exist for their optimal management. The purpose of this study was to review the management and longterm prognosis of head and neck plexiform neurofibromas and schwannomas at 2 tertiary care academic hospitals in Finland over a 31-year period. The pathology files were searched for plexiform neurofibromas and schwannomas between the years 1990 and 2020. The case notes were reviewed for full management details. Two plexiform schwannomas and 6 plexiform neurofibromas were identified. Five of the 6 plexiform neurofibromas were managed operatively. All patients with a surgically managed plexiform neurofibroma underwent multiple operations. Sclerotherapy abolished 1 patient's cutaneous plexiform neurofibromas. The management of plexiform neurofibromas and plexiform schwannomas remains challenging. Sclerotherapy may offer a promising management option for cutaneous plexiform neurofibromas.Peer reviewe

Disorders of sex development : timing of diagnosis and management in a single large tertiary center

Background: We describe the phenotypic spectrum and timing of diagnosis and management in a large series of patients with disorders of sexual development (DSD) treated in a single pediatric tertiary center. Methods: DSD patients who had visited our tertiary center during the survey period (between 2004 and 2014) were identified based on an ICD-10 inquiry, and their phenotypic and molecular genetic findings were recorded from patient charts. Results: Among the 550 DSD patients, 53.3% had 46,XY DSD; 37.1% had sex chromosome DSD and 9.6% had 46,XX DSD. The most common diagnoses were Turner syndrome (19.8%, diagnosed at the mean age of 4.7 +/- 5.5 years), Klinefelter syndrome (14.5%, 6.8 +/- 6.2 years) and bilateral cryptorchidism (23.1%). Very few patients with 46,XY DSD (7%) or 46,XX DSD (21%) had molecular genetic diagnosis. The yearly rate of DSD diagnoses remained stable over the survey period. After the release of the Nordic consensus on the management of undescended testes, the age at surgery for bilateral cryptorchidism declined significantly (P <0.001). Conclusions: Our results show that (i) Turner syndrome and Klinefelter syndrome, the most frequent single DSD diagnoses, are still diagnosed relatively late; (ii) a temporal shift was observed in the management of bilateral cryptorchidism, which may favorably influence patients' adulthood semen quality and (iii) next-generation sequencing methods are not fully employed in the diagnostics of DSD patients.Peer reviewe

Carcinoembryonic antigen in retinoblastoma. An immunohistochemical study.

Pathological amounts of carcinoembryonic antigen (CEA) have earlier been reported in the plasma of patients with retinoblastoma, and it has been suggested that CEA determinations be used in the follow-up of treatment of these patients. In the present study, 47 retinoblastoma specimens from the years 1962-1982 were examined. These specimens represented different clinical and pathological tumour types. Colon adenocarcinomata positive for CEA were used as controls. The laboratory method was a highly sensitive immunohistochemical peroxidase-staining procedure. By this method, CEA was not found in any of the retinoblastomata examined. It is probable that retinoblastoma does not produce CEA, but in theory it may indirectly increase the CEA titre or, on the other hand, be fully independent of CEA. Only after this relationship has been thoroughly clarified can determinations of plasma CEA in patients with retinoblastoma be used in clinical work.Peer reviewe

Ear canal and middle-ear tumors : a single-institution series of 87 patients

Background Ear canal and middle ear tumors are rare and exhibit variability in histology and clinical manifestation. Surgical resection remains the treatment of choice, but individualized approach is needed to preserve function when possible. Aims/objectives To review the management and outcome of ear canal and middle ear tumors at an academic referral center. Materials and methods Helsinki University Hospital (HUS) patient files were searched for clinically and histologically confirmed ear canal and middle ear tumors over a 14-year period. The minimum follow-up time was 2 years. Results Eighty-seven patients with 88 tumors were identified. There were 20 (23%) benign external auditory canal (EAC), 36 (41%) benign middle ear space (MES), 29 (33%) malignant EAC, and 3 (3%) malignant MES tumors. Most (92%) tumors were managed with primary resection. Thirty-five percent of the operatively managed patients had a residual or a recurrent tumor. Conclusions and significance EAC and MES tumors show great diagnostic and histologic heterogeneity with need for individualized investigative and treatment approaches. In benign tumors, we advocate aggressive local surgical control without sacrificing vital structures. In malignant tumors, we recommend local surgical control with or without adjunct RT.Peer reviewe

Repeatedly recurring pleomorphic adenoma : a therapeutic challenge

Pleomorphic adenoma (PA) is the most common tumour of the salivary glands, and can recur even after proper surgery. The extent and timing of surgery for recurrent tumours remains controversial, and multiple recurrences pose a special challenge. We evaluated all recurrent PAs (RPAs) treated at the Helsinki University Hospital through 2004-2013 focusing on patients with multiple recurrences. Follow-up data were obtained until January 2018. Of the 47 patients, 70% were women and the median age was 33.5 years. Most of the RPAs were located in the parotid gland (87%), and six (13%) in the submandibular gland. One-third (17/47) of tumours had been primarily excised. This patient population experienced 75 recurrent events in total with two or more recurrences in 14 patients (30%). The time interval between recurrences shortened after each recurrent event and the tumour was more likely to be multifocal. At the end of the follow-up period, 15% had recurrent disease and malignant transformation had occurred in 6%. Treatment for PA and RPA is challenging and requires centralised management. Patients with RPA are often young and recurrences may cause lifelong morbidity, especially when the tumour recurs repeatedly. The utilisation and timing of postoperative radiotherapy needs to be discussed as well as the potential risk for malignant transformation in this patient population.Peer reviewe

Evaluation of LOXL1 gene polymorphisms in exfoliation syndrome and exfoliation glaucoma

Purpose: To evaluate genetic susceptibility of lysyl oxidase-like 1 (LOXL1) gene polymorphisms to exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) in a case-control cohort of American and European patients. Methods: DNA from a total of 620 individuals including 287 exfoliation patients and 333 healthy control subjects were extracted by standard methods. Three single nucleotide polymorphisms (SNPs) of rs1048661 (R141L), rs3825942 (G153D), and rs2165241 were genotyped in these individuals by SNaPshot Assay. The seven coding exons of the LOXL1 gene and their immediate flanking regions were directly sequenced in 95 affected patients. Data management and case-control association studies were performed with SNP-STAT and PLINK programs. The obtained DNA sequences were evaluated with the STADEN package. Results: The 287 unrelated exfoliation cases comprised of 171 American patients (mostly of European background) and 116 patients from 12 European countries. This phenotype was further divided into patients with exfoliation only and no glaucoma (XFO; n=95), exfoliation with glaucoma (XFG; n=133), and exfoliation unclassified (XFU; n=59). Genotypic data were analyzed separately for XFO, XFG, XFU, and XFS (all exfoliations; n=287) and for Americans and Europeans. The observed genotypic frequencies for each exfoliation phenotype or population were tabulated separately and tested for deviation from the Hardy–Weinberg equilibrium (HWE) using a standard Χ2 test. There were no HWE deviations and no significant genotypic differences between these subcategories for the three studied SNPs. For the combined exfoliation cohort, homozygote genotypes of G/G (rs1048661), G/G (rs3825942), and T/T (rs2165241) were significantly overrepresented. Likewise, case-control allelic association for rs1048661 (p=7.74x10−9), rs3825942 (p=3.10x10−17), and rs2165241 (p=4.85x10−24) were highly significant. The corresponding two-locus haplotype frequencies of GG for rs1048661-rs3825942 (p=1.47x10−27), GT for rs1048661-rs2165241 (p=1.29x10−24), and GT for rs3825942-rs2165241 (p=2.02x10−24) were highly associated with exfoliation phenotypes. The combined effect of these three SNPs revealed that the GGT haplotype is overrepresented by 66% in exfoliation cases, and this deviation from controls is highly significant (p=1.93x10−24). This haplotype constituted a major risk factor for development of exfoliation in both XFS and XFG. By contrast, the GAC haplotype was significantly underrepresented (p=4.99x10−18) in exfoliation cases by 83% and may potentially have a protective effect for this condition with an estimated attributable risk percent reduction of 457%. The only other haplotype that was significantly different between cases and controls was TGC (p=5.82x10−9). No observation was made for the GAT haplotype. The combined three haplotypes of GGT, GAC, and TGC were associated with 91% of the exfoliation syndrome cases in the studied populations. Seven coding exons of LOXL1 were also sequenced in 95 affected cases. In addition to the three above-mentioned SNPs, 12 other variations were also observed in these patients(G240G, D292D, A320A, V385V, rs2304719, IVS3+23C>T, IVS3–155G>A, IVS3–101G>A, IVS4+49G>A, rs2304721, IVS5–121C>T, and rs2304722). None were considered a disease-causing mutation. Conclusions: We confirmed a strong association with LOXL1 variants in our patients. For the LOXL1 gene, individual alleles of rs1048661 (G), rs3825942 (G), and rs2165241 (T) are highly associated with XFS and XFG in American and European populations. The GGT haplotype constitutes a major risk haplotype for exfoliation, and GAC may have a protective role. DNA sequencing of 95 affected patients did not show any mutations in this gene. The LOXL1 SNPs are located in the 15q24.1 band and within a genetic locus (GLC1N) that is associated with primary open-angle glaucoma (POAG). However, the LOXL1 genetic predisposition is only limited to exfoliation with or without glaucoma and does not include the POAG phenotype