Molecular analysis of NUT-positive poromas and porocarcinomas identifies novel break points of YAP1::NUTM1 fusions.

BACKGROUND: Poromas, and their malignant counterparts, porocarcinomas, harbor recurrent translocations involving YAP1-MAML2, YAP1-NUTM1, and infrequently WWTR1-NUTM1; YAP1-NUTM1 being the most common in porocarcinomas. NUT immunohistochemistry (IHC) can be used to identify NUTM1-translocated tumors. This study sought to investigate potential novel NUTM1-fusion partners among NUT IHC-positive poromas and porocarcinomas. METHODS: Thirteen NUT IHC-positive poroid tumors (four poromas and nine porocarcinomas) were identified within a multi-institutional international cohort. Next-generation sequencing (NGS) assessed for NUTM1 fusion partners. RESULTS: NGS detected a NUTM1 fusion in 12 of 13 cases: YAP1-NUTM1 (11/12 cases) and WWTR1-NUTM1 (1/12 cases). Two of the cases (2/12) with NUTM1 fusion were not called by the NGS algorithm but had at least one read-spanning YAP1-NUTM1 break point upon manual review. A NUTM1 fusion was not identified in one case; however, the sample had low RNA quality. The following fusion events were identified: YAP1 exon 4::NUTM1 exon 3 in six cases, YAP1 exon 6::NUTM1 exon 2 in one case, YAP1 exon 3::NUTM1 exon 3 in three cases, WWTR1 exon 3::NUTM1 exon 3 in one case, and YAP1 exon 8::NUTM1 exon 3 fusion in one case. CONCLUSION: While no novel NUTM1 fusion partners were identified within our cohort, 12 of 13 cases had discoverable NUTM1 fusions; YAP1-NUTM1 fusion was detected in 11 cases (92%) and WWTR1-NUTM1 in 1 case (8%). These data corroborate findings from other recent investigations and further substantiate the utility of NUT IHC in diagnosing a subset of poroid neoplasms. In addition, two of our cases harbored fusions of YAP1 exon 6 to NUTM1 exon 3 and YAP1 exon 8 to NUTM1 exon 2, which have not been reported before in poroid neoplasms and indicate novel break points of YAP1.

The management of locally advanced head and neck squamous and basal cell carcinomas.

PURPOSE: The management of locally advanced head and neck basal (BCC) and squamous cell (SCC) carcinomas has been controversial and often debated. The purpose of the current study was to present our experience in the treatment of non-melanotic head and neck skin malignancies. METHODS: From 2000 to 2017, 34 patients with locally advanced head and neck skin tumors were treated in our hospital with wide local excision and immediate reconstruction mainly with rotational flaps, free tissue transfers and skin grafting. RESULTS: Histopathological examination revealed 10 BCCs, 22 SCCs and 2 cases of metatypical basal cell carcinomas. All patients were successfully submitted to ablative procedure with minimal morbidity and acceptable cosmetic results. CONCLUSIONS: Locally advanced head and neck SCCs and BCCs are large tumors that may invade adjacent structures or infiltrate into deep tissues. Complex reconstructive methods are needed to close the defect, with free tissue transferring being a reliable option. Finding clear margins is crucial in order to prevent unnecessary morbidity and local recurrence.

Tracking the risk factors associated with high-risk cSCC: A 10-year, Two-Institution, Greek study.

PURPOSE: We sought to identify independent risk factors for positive sentinel lymph node biopsy (SLNB), local recurrence (LR), metastasis (M) and death caused by cutaneous squamous cell carcinoma (cSCC) (DCS) in high-risk cSCC patients. Moreover, we compared the Brigham and Women's Hospital (BWH) system with the previous used in Greece (based on tumor size) and proposed a new classification system. METHODS: 1,524 cSCC patients were enrolled between January 2004 and December 2014, from two medical institutions. Potential risk factors for SLNB (local recurrence/LR, metastasis/M, death caused by SCC/DCS) were analyzed by univariate and multivariate Cox logistic regression models. RESULTS: Of the included patients with a median follow-up of 60 months 107 developed local recurrence (7%) while 84 developed metastases (5.5%). Among 36 patients undergoing sentinel lymph node biopsy (SLNB), 25% showed a positive SLNB with a false-negative result (11%). On multivariate analysis, key prognostic factors for LR were tumor diameter ≥2 cm, poor differentiation, incomplete excision and perineural invasion and for M were high-risk tumor site, tumor diameter ≥2 cm, poor differentiation, invasion beyond subcutaneous tissue, incomplete excision, perineural invasion and recurrence. DCS seems to be affected by tumor diameter ≥ 2 cm, poor differentiation, invasion beyond subcutaneous tissue, incomplete excision, perineural invasion and recurrence independently. CONCLUSIONS: These suggest the determined role of tumor diameter of cSCCs. Harnessing knowledge and collecting the up-to-date data along the clinical journey of high-risk cSCC, the future looks bright (development of new clinical trials, adjuvant therapies and tumor staging with SLNB).

Perineal Reconstruction with a Diamond-shaped Perforator Flap: A Case Report.

Reconstruction of perineal defects is a challenging procedure. Various surgical techniques have been proposed. Compared with traditional myocutaneous flaps, pedicled perforator flaps are believed to be a less invasive option for perineal reconstruction, with better functional and cosmetic results. We present the case of a 47-year-old woman with a perianal Paget's disease who underwent surgical excision of the lesion. The reconstructive technique was a pedicled flap based on an internal pudendal skin perforator artery. The flap was designed in a diamond-shaped pattern. Six months after the operation, the patient is disease-free with successful aesthetic and functional results. A polygonal diamond-shaped flap is an easy and reliable choice for perineal reconstruction, offering better adjustment in the perianal region and avoidance of the curvilinear perianal incision (which often leads to anal stenosis).

The Anterolateral Thigh Perforator Flap in an Innovative Microsurgery Training Method.

The road to becoming a good and confident microsurgeon requires love for your work, patience, and good training facilities. Safe and effective training procedures for young microsurgeons during their plastic surgery residency are necessary and should be applied under standardized conditions. We present an innovative microsurgical training method for plastic surgery residents in the operation theater concerning the anterolateral thigh perforator flap (ALT). In a 2-team approach, the ALT flap harvesting begins parallel to tumor resection. Although the tumor excision team still works in the tumor region, and after the reconstructive team has successfully completed the ALT dissection, residents can work distally to the origin of the perforator vessel (which supplies the flap). Their training involves dissection and anastomosis of the continuation of the descending branch, distally to the perforator supplying the flap. Since 2015, eight operations have been performed with this innovative method with the participation of upcoming microsurgeons. A written informed consent is given to all patients. Our study resulted in the improvement of microsurgical skills of the young microsurgeons. There is no impact to the ALT perforator flap or to the operative time. This training procedure can be safely applied as a training method during plastic surgery residency under standardized conditions. We have the joy of seeing our resident's progress through their high success rates in microsurgery. We recommend this innovative procedure as an adequate teaching method during residency to promote the future of our specialty, and we hope that our students will become even better than their teachers.

Intramuscular granular cell tumor of the gluteal region.

Granular cell tumors are uncommon, usually benign neoplasms, mainly observed in the head and neck region, chest wall and upper extremities. These tumors account for ~0.5% of all soft-tissue tumors. Less than 2% are malignant. These are associated with poor prognosis. Clinical signs suspicious for malignancy are large size, rapid growth, invasion, recurrence and metastasis. Malignancy is confirmed by histological examination. We present the case of a 79-year-old patient with a 6-month history of a rapidly growing mass in the left gluteal region giving the clinical impression of a malignant tumor. The patient underwent surgical excision of the tumor and the pathology report revealed a granular cell tumor. In difficult cases, multidisciplinary approach is necessary for appropriate diagnosis and management.

Dermatofibrosarcoma protuberans coexisting in a patient with a vascular malformation-a rare coincidence.

Dermatofibrosarcoma protuberans with fibrosarcomatous differentiation (DFSP-FS) is a rare soft tissue tumor with more aggressive behavior and it is not clear what causes this type of skin cancer. We describe the case of a 48-year-old woman who was born with a vascular malformation in the sternal region and presented suddenly with a soft tissue sarcoma (DFSP-FS) in the same territory. She was initially treated by embolization as the sarcoma was misdiagnosed but the tumor within 6 months seemed to be growing rapidly and reached a giant dimension with ulceration and required surgical intervention. The patient underwent a surgical removal of the mass but as the pathology report included a DFSP-FS with close margins,a second operation was required. A wide local excision was performed and reconstruction of defect by using bilateral pectoralis major muscle flaps and a full thickness skin graft from the abdominal wall. Post operatively the patient was treated with radiotherapy.

Gastrocnemius muscle flap of both heads on a single vascular pedicle.

We present a case of a muscle flap of both heads of gastrocnemius on a single vascular pedicle for reconstruction of a tibial defect. The flap was based on the medial sural vessels alone. The vascular supply to the lateral head was achieved through the anastomotic vessels along the gastrocnemial raphe.