Clinical characteristics and genetic testing outcome of suspected hereditary peripheral nerve sheath tumours in a tertiary cancer institution in Singapore.

BACKGROUND: Peripheral Nerve Sheath Tumors (PNST) are a diverse group of mostly benign tumours uncommon in the general population. About 5-10% of PNSTs are hereditary, predominantly arising from germline variants in NF1, NF2, SMARCB1, or LZTR1 gene. METHODS: We reviewed the clinical characteristics and genetic testing results of patients referred to the NCIS Adult Cancer Genetics Clinic for suspected hereditary PNST. RESULTS: 3,001 patients suspected to have various hereditary cancer syndromes were evaluated between year 2000 to March 2021. 13 (0.4%) were clinically diagnosed to have hereditary PNSTs. The majority were male (54%), with a median age at presentation to the genetics clinic of 29 years (range 19-48). 11/13 (85%) patients had multiple PNSTs, 12/13 (92%) had young onset PNSTs, 5/13 (38.5%) had personal and family history of PNST. 11/13 patients (85%) had clinical features of neurofibromatosis type 1 (NF1) including one patient who also fulfilled clinical criteria of neurofibromatosis type 2 (NF2); 2/13 (14%) had multiple schwannomas. Four patients underwent multi-gene panel testing, including one patient with clinical NF1, one patient who met both clinical NF1 and NF2 criteria, and two patients with multiple schwannomas. The patient with clinical features of NF1 was heterozygous for a pathogenic c. 2033dup variant in the NF1 gene. The patient with both NF1/NF2 features was heterozygous for a novel c.732 T > A nonsense variant in the NF2 gene. The two patients with multiple schwannomas were heterozygous for a pathogenic/likely pathogenic variant in the LZTR1 gene and are the first LZTR1-positive schwannomatosis patients reported in Asia. CONCLUSION: Hereditary PNSTs are rare referrals to an adult cancer genetics clinic. NF1 is the most common PNST seen. LZTR1 variants may be the underlying cause in Asian patients with multiple schwannomatosis.

Pigmented Nail Lesions: When to Observe, When to Biopsy, When to Widely Excise, and When to Amputate?

Pigmented nail lesions are challenging problems. The differential diagnosis is broad and ranges from common self-limiting conditions, such as subungual hematoma and infection, to potentially fatal conditions, such as subungual melanoma. Clinical assessment and adjuncts, such as dermoscopy and imaging, are usually insufficient to establish a diagnosis, and a nail bed biopsy is often required. However, this is not an innocuous procedure and may result in permanent nail deformity. In addition, subjecting every patient with nail pigmentation to a biopsy will result in an unacceptably high rate of negative test results. Furthermore, histopathologic diagnosis of subungual melanoma remains challenging for several reasons. Once the diagnosis of subungual melanoma is established, the definitive treatment is controversial because the existing guidelines have largely been adapted from those for cutaneous melanoma. This review presents an approach to the diagnosis and management of pigmented subungual lesions and subungual melanoma, in particular, on the basis of the latest available evidence.

The treatment landscape of advanced angiosarcoma in Asia-A multi-national collaboration from the Asian Sarcoma Consortium.

Angiosarcoma (AS) is a rare disease with a dismal prognosis. The treatment landscape and prognostic factors for advanced AS, including locally advanced, unresectable, and metastatic disease remain elusive. The Asian Sarcoma Consortium is an international collaborative effort to understand the sarcoma treatment landscape in Asia. We undertook a retrospective chart review of AS patients seen in 8 sarcoma academic centers across Asia. Patients with complete clinical, treatment, and follow-up data were enrolled. Overall, 276 advanced AS patients were included into this study; 84 (30%) of the patients had metachronous metastatic AS. The median age was 67 y; primary sites of AS was cutaneous in 55% and visceral in 45% of patients. In total, 143 (52%) patients received at least 1 line of systemic chemotherapy. The most common first-line chemotherapy regimen used was paclitaxel (47.6%) followed by liposomal doxorubicin (19.6%). The median overall survival (OS) was 7.8 mo. Significant prognostic factors for OS included age > 65 (hazard ratio (HR) 1.54, P = .006), male gender (HR 1.39, P = .02), and a cutaneous primary AS site (HR 0.63, P = .004). The median progression-free survival (PFS) for first-line chemotherapy was 3.4 mo. PFS for single vs combination or paclitaxel vs liposomal doxorubicin chemotherapy regimens were comparable. This study provides an insight into the treatment patterns and prognostic factors of advanced AS patients in Asia. Prognosis of advanced AS remains poor. Data from this study serve as a benchmark for future clinical study design.

Sarcoma of the Lower Limb: Reconstructive Surgeon's Perspective.

Management of sarcomas in the lower extremities have evolved from amputations to limb-preserving surgeries with evidence to support that they have equal overall survival, albeit with better functional outcome. The challenge of reconstruction lies in providing a durable, functional, and aesthetically pleasing limb. However, limb-preserving intention should not delay interventions that provide a survival benefit such as chemotherapy and radiotherapy. The advent of radiotherapy and chemotherapy also has implications on wound healing and should be considered during the reconstructive process. This article reviews the methodical approach, reconstructive strategies, and considerations for the reconstructive surgeon with respect to the lower extremity after sarcoma excision.

Angiomatoid Fibrous Histiocytoma With Prominent Myxoid Stroma: A Case Report and Review of the Literature.

Angiomatoid fibrous histiocytoma is a rare neoplasm of intermediate malignant potential that usually occurs in the dermis or subcutaneous tissues of the extremities in children or young adults. It is characterized by a nodular growth of spindled, histiocytic, or epithelioid cells and blood-filled spaces, surrounded by a fibrous pseudocapsule that contains a lymphocytic cuff. The histological spectrum of this condition has expanded to include cases that contain prominent myxoid stroma. We herein present another instance of myxoid angiomatoid fibrous histiocytoma and review the clinical and histological features, immunohistochemical profile, and molecular genetics of this uncommon variant. We also discuss the diagnostic mimics of this condition, including benign myxoid soft tissue tumors and sarcomas, to illustrate the potential pitfalls in arriving at the diagnosis.

The dorsal metatarsal artery perforator flap.

Few options exist for the resurfacing of web-space and small soft tissue defects of the dorsum of the distal foot. The study examines the anatomy of the second to fourth dorsal metatarsal arteries in 16 fresh frozen cadavers to determine if the anatomy correlates to that in the hand, permitting the design of local flaps based on perforators of these vessels. A clinical case is also presented, illustrating the efficacy of such a perforator-based flap.Sixteen Asian cadaveric lower limbs were used for this study. The specimens were prepared with latex dye injection. Dissection under loupe magnification was carried out to determine the position and caliber of the cutaneous perforators from the dorsal metatarsal arteries, and the spread of the latex dye in the skin from these cutaneous perforators. One clinical case illustration of this perforator-based flap for distal foot defect resurfacing is presented.In our cadaveric study, each second to fourth dorsal metatarsal artery had between 2 and 5 cutaneous perforators with calibers of 0.5 to 0.7 mm in diameter. The most distal cutaneous perforator was present consistently, always arising between the heads of the respective metatarsals.In conclusion, the vascular anatomy of the second to fourth dorsal metatarsal arteries is similar to that in the hand, thus allowing for the design of reliable perforator-based flaps for distal foot resurfacing.

Radiation-induced osteosarcoma of the hand: case report.

Radiation-associated sarcomas represent less than 5% of all sarcomas and can arise from previously irradiated bone or soft tissue. We report a case of radiation-associated osteosarcoma that developed in the hand of a patient who had previously been treated for synovial sarcoma. Despite aggressive, multimodality treatment, the disease progressed rapidly. This case highlights the need for patients and treating physicians to be aware of this potential complication of radiotherapy to the hand.

Artificial Intelligence in Hand Surgery - How Generative AI is Transforming the Hand Surgery Landscape.

Artificial intelligence (AI) has witnessed significant advancements, reshaping various industries, including healthcare. The introduction of ChatGPT by OpenAI in November 2022 marked a pivotal moment, showcasing the potential of generative AI in revolutionising patient care, diagnosis and treatment. Generative AI, unlike traditional AI systems, possesses the ability to generate new content by understanding patterns within datasets. This article explores the evolution of AI in healthcare, tracing its roots to the term coined by John McCarthy in 1955 and the contributions of pioneers like John Von Neumann and Alan Turing. Currently, generative AI, particularly Large Language Models, holds promise across three broad categories in healthcare: patient care, education and research. In patient care, it offers solutions in clinical document management, diagnostic support and operative planning. Notable advancements include Microsoft's collaboration with Epic for integrating AI into electronic medical records (EMRs), enhancing clinical data management and patient care. Furthermore, generative AI aids in surgical decision-making, as demonstrated in plastic, orthopaedic and hepatobiliary surgeries. However, challenges such as bias, hallucination and integration with EMR systems necessitate caution and ongoing evaluation. The article also presents insights from the implementation of NUHS Russell-GPT, a generative AI chatbot, in a hand surgery department, showcasing its utility in administrative tasks but highlighting challenges in surgical planning and EMR integration. The survey showed unanimous support for incorporating AI into clinical settings, with all respondents being open to its use. In conclusion, generative AI is poised to enhance patient care and ease physician workloads, starting with automating administrative tasks and evolving to inform diagnoses, tailored treatment plans, as well as aid in surgical planning. As healthcare systems navigate the complexities of integrating AI, the potential benefits for both physicians and patients remain significant, offering a glimpse into a future where AI transforms healthcare delivery. Level of Evidence: Level V (Diagnostic).

Challenges and Solutions in Prosthetic Fitting of Digits after Flap Reconstruction.

Surgical reconstruction can restore length and function, but cannot adequately resolve the problem of disfigurement. Prosthetic fitting can play a complementary role in enhancing the aesthetic outcomes post reconstruction. However, complex reconstruction involving flaps coupled with the surgical imperative for limb length preservation can lead to outcomes where the reconstructed stumps are challenging to fit with prosthesis. This article describes how prosthetic fitting was tackled in a case of a triple-digit amputation after reconstruction that presented with finger stumps that were bulky, long and stiff in extension contracture, compounded by the presence of substantive scar tissues. We discuss major prosthesis modifications that were unconventional but necessary to enable fitting, the techniques involved, as well as the aesthetic and functional considerations behind the modifications. The results showed that enhanced aesthetic appearance, together with a marginal improvement in hand function, was achieved post-prosthetically, meeting the patient's and the clinical team's fitting objective. Level of Evidence: Level V (Therapeutic).

Color-matching techniques for creating esthetic hand and finger prostheses.

BACKGROUND: Color matching is a critically important part of, and by far, also the most challenging aspect of producing esthetic silicone prosthesis. There is a knowledge gap in the literature and a lack of opportunities for training in the expertise, particularly regarding color-matching techniques. OBJECTIVE: This article details a color-matching technique that is able to achieve life-like coloration in esthetic prosthesis. TECHNIQUE: Each prosthesis is molded in an outer and inner layers of silicone tinted to different shades and opacities incorporating an intermediate touch-up layer to reproduce the detailed coloration of the hand (because of the presence of veins, finger joint/dermal pigmentations, a vascularized nail bed, and pinkish palm). This method of color-matching prosthesis combining intrinsic and extrinsic techniques simulates the layered anatomy and optical properties of the human skin to effectively replicate its esthetic and life-like coloration. Technical tips for achieving an accurate color match to the patient's skin, including pigment formulation adjustments for a tanned vs. a fair skin, and for painting the touch-up details are discussed. Methods for modifying the color tones of completed prosthesis and for minimizing metameric color differences when the prosthesis is viewed under different light sources are also presented. DISCUSSION: The technique is instrumental in achieving good outcomes for life-likeness and esthetic coloration in the prostheses fitted at our center. Studies previously published that investigated patients' evaluation of important esthetic characteristics of their prosthesis after a period of adjustment to fitting have shown a generally high level of patient satisfaction.

Functional use of esthetic hand prosthesis: A patient's perspective.

Published reports on the functional benefits of esthetic prosthesis are based on either anecdotal evidence or simplified, nonstandard forms of hand function evaluation performed by the researcher. It is not clear whether and how patients actually make functional use of their prosthesis on a daily basis. We report a case of a patient with a partial hand amputation who was initially ambivalent about fitting an esthetic prosthesis, but went on to make functional use of her prosthesis for activities of daily living, work, and social life at 3 years after injury. We present the patient's own assessment and video recordings, made without influence from rehabilitation personnel that demonstrates this functional use. From this case, we discuss the important factors of a favorable residual limb type, together with targeted modifications made to the prosthesis to optimize function.

Major upper-limb amputations for malignant tumors.

PURPOSE: With the continued advancement of limb salvage surgery, major upper-limb amputations are being performed less frequently and are generally reserved for patients with large, multifocal, or recurrent tumors for whom limb salvage is no longer an option. We conducted a retrospective review of the current indications and patient outcomes after major upper-limb amputations for malignant tumors. METHODS: Using the institution surgical database, we identified 43 patients who underwent major upper-limb amputation for primary and metastatic malignant tumors from 1996 to 2008. RESULTS: Of these 43 patients, 25 had soft tissue sarcoma, 7 had bone sarcoma, and 11 had carcinoma. Two patients had stage I, 3 had stage II, 21 had stage III, and 17 had stage IV disease. We performed 45 amputations: 5 below the elbow, 14 above the elbow, and 26 at the forequarter. Among the 45 amputations, 2 patients underwent a second more proximal amputation for local tumor recurrence. Of the 17 patients with stage IV disease, 10 underwent palliative amputation for symptom control. A total of 28 patients (65%) died. Median survival after amputation was 13 months (95% confidence interval, 8-19 mo). The 6-month cumulative incidence of local recurrence was 22%. Overall survival after forequarter amputations was 42% at 1 year. CONCLUSIONS: Survival after major upper-limb amputation is poor, especially because amputations are reserved for patients with advanced tumors. However, amputation remains an option for local tumor control and can palliate symptoms in selected patients. Improvement of survival requires more effective systemic treatment strategies. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Predictors and Treatment Outcomes of Pediatric Osteosarcoma in Diverse Socioeconomic Backgrounds in Southeast Asia: A Retrospective Multicenter Study.

BACKGROUND: Pediatric osteosarcoma outcomes among developed and developing countries have not been previously compared. Countries in Southeast Asia (SEA) have a wide variety of socioeconomic statuses. A multi-institutional retrospective study was conducted to determine the prognostic factors and outcomes for pediatric osteosarcoma in SEA. METHODS: Pediatric patients with osteosarcoma treated between 1998 and 2017 in 4 SEA pediatric oncology centers were studied. Countries were classified using the World Bank Atlas method. Kaplan-Meier method and Cox's Proportion Hazard Model were applied to estimate survival outcomes and identify prognostic factors. RESULTS: In all, 149 patients with osteosarcoma with a mean age of 12.48±3.66 years were enrolled. The localized to metastatic disease ratio was 1.5:1. The 5-year overall survival (OS) and event-free survival (EFS) were 53.8% and 42%, respectively. Prognostic factors associated with outcomes were country, stage of disease, MTX-containing regimens, and surgery type (p-value <0.05). In patients with localized disease, EFS was superior with limb-salvage surgery (62%) than amputation or rotationplasty (40%) (p-value 0.009). MTX-containing chemotherapies provided higher OS (45.3%) and EFS (37.9%) than non-MTX regimens (12.3% and 10.7%, respectively) among metastatic patients (p-value 0.004 and 0.005, respectively). Metastatic disease was an independent prognostic factor for death but not relapse outcome.  Conclusion: The disease outcomes in SEA were acceptable compared to developed countries. The stage of disease was the only independent prognostic factor. MTX-containing regimens and limb-salvage surgery should be considered where possible.

Double ray amputation for tumors of the hand.

BACKGROUND: Partial hand amputations for malignant tumors allow tumor resection with negative resection margins, which is associated with lower local recurrence rates and improved overall survival while preserving native tissue, which improves functional outcome. QUESTIONS/PURPOSES: We conducted this study to assess the functional outcome of double ray amputations of the hand. METHODS: We retrospectively reviewed the records of five patients who underwent double ray amputations at our center over 12 years: four amputations of the fourth and fifth rays and one amputation of the second and third rays. Mean age at surgery was 34 years (range, 10-45 years), and minimum followup was 64 months (mean, 98 months; range, 64-136 months). All five patients had high-grade soft tissue sarcomas of the hand, two synovial sarcomas, two malignant peripheral nerve sheath tumors, and one undifferentiated sarcoma. No patients had detectable metastases at surgery. RESULTS: Four of the five patients were completely disease-free at latest followup. One patient was alive with lung metastases detected 32 months after surgery. No patients developed local tumor recurrence. Functional assessment showed a mean Musculoskeletal Tumor Society score of 24 (range, 19-28) and mean grip strength 24% of the contralateral side (range, 17%-35%). CONCLUSIONS: Although double ray amputation results in worse functional outcome than single ray, good key, tip, and tripod pinch can be preserved when the deep motor branch of the ulnar nerve is preserved, and this hand can still assist in bimanual hand activities. Our observations suggest double ray amputation is an acceptable hand-preserving procedure.

Malignant and metastatic tumors of the hand.

Malignant tumors of the hand are rare, although there remain many instances in which marginal excisions are performed for unsuspected malignant hand lesions. Suboptimal biopsy incisions and inadvertent contamination during these excisions may result in larger resections or amputations being necessary to ensure complete removal of the tumor with negative margins. This article provides an update for the current management of patients with primary malignant and metastatic tumors of the hand, including the roles of adjuvant radiotherapy and chemotherapy for the more common hand tumors.

Partial hand preservation for large soft tissue sarcomas of the hand.

PURPOSE: Hand amputations cause marked functional loss for patients. In patients with large soft tissue sarcomas of the hand, partial hand preservation is extremely challenging for surgeons attempting a complete resection of the tumor with negative resection margins. We conducted this review to examine the oncologic outcome, including local recurrence rate and patient overall survival, and functional outcome after resections for large soft tissue sarcomas with partial hand preservation. METHODS: We performed a retrospective review of all patients with soft tissue sarcomas of the hand treated at our institution from 1995 to 2007. We identified 8 patients who had tumors at least 5 cm in maximum dimension and had tumor resection with partial hand preservation. The mean age at the time of surgery was 49 years (range, 10-80 years). Two patients had myxofibrosarcoma, 2 patients had synovial sarcoma, 2 patients had malignant fibrous histiocytoma, 1 patient had a malignant peripheral nerve sheath tumor, and 1 patient had a liposarcoma. Two patients had low-grade tumors, and 6 patients had high-grade tumors. Two patients had American Joint Committee on Cancer stage 1b tumors, and 6 patients had American Joint Committee on Cancer stage 3 tumors. No patients had distant metastases at the time of surgery. Hand function was evaluated using Musculoskeletal Tumor Society criteria. RESULTS: Of the 8 patients, 1 died of distant metastatic disease, 1 developed local tumor recurrence and is alive with locally recurrent disease, and the other 6 patients are completely disease-free. The mean Musculoskeletal Tumor Society score was 26 (range, 19-29), with the 2 patients who had received double-ray amputations having the lower scores (19 and 24). CONCLUSIONS: Partial hand preservation is possible in selected patients with large soft tissue sarcomas of the hand, obtaining low local recurrence rates, good overall survival, and good functional outcome. However, all effort should be made to achieve negative resection margins. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Predictive value of magnetic resonance imaging in determining presence of residual disease after marginal excision of unsuspected soft tissue sarcomas of the hand.

PURPOSE: Diagnosis of a soft tissue sarcoma of the hand is at times made only in retrospect after marginal excision of a presumed benign soft tissue mass. Magnetic resonance imaging (MRI) helps determine the presence of residual disease and the extent of contamination caused by marginal excision of unsuspected soft tissue sarcomas and assists in the planning of definitive treatment with surgery and radiotherapy when required. We sought to determine the accuracy of MRI in detecting residual sarcoma after marginal excision. METHODS: We retrospectively studied case records and imaging studies for all patients with soft tissue sarcomas of the hand evaluated and treated at our institution from 1996 to 2005. We included in this study 33 patients who underwent definitive surgery at our center after prior marginal excision. MRI scans done before definitive wide resection were classified as positive or negative for residual tumor. A musculoskeletal radiologist, blinded to the sarcoma type, findings on histopathology, and surgery, reviewed 19 scans to see whether the accuracy could be improved. RESULTS: There were 8 epithelioid sarcomas, 6 synovial sarcomas, 4 malignant fibrous histiocytomas, 2 leiomyosarcomas, 2 liposarcomas, 2 myxofibrosarcomas, and one each of 9 other diagnoses. A total of 11 were low-grade and 22 were high-grade tumors, with 4 superficial and 29 deep tumors. Pathology examination after definitive wide resection or partial hand amputation showed that 15 patients had residual tumor, 9 gross and 6 microscopic. The sensitivity of MRI in detecting residual soft tissue sarcoma of the hand was 60%, specificity was 78%, positive predictive value was 69%, and negative predictive value was 70%. The sensitivity of MRI in detecting gross residual soft tissue sarcoma of the hand was 89%, specificity was 79%, positive predictive value was 62%, and negative predictive value was 95%. Even when an experienced musculoskeletal radiologist reassessed 19 MRI scans, the accuracy did not improve. CONCLUSIONS: Magnetic resonance imaging does not reliably detect residual gross or microscopic soft tissue sarcoma after marginal excision of unsuspected soft tissue sarcomas of the hand, with residual tumor not readily distinguished from postoperative change. The absence of disease on MRI should not be used as the sole criterion in determining whether a repeat resection should be performed. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.

Complications of radiation therapy to the hand after soft tissue sarcoma surgery.

PURPOSE: Radiation has been shown to improve local control after resection of soft tissue sarcomas. However, it may also result in major complications in the hand, given the compact nature of functional tissues and limited tissue volumes in the hand. The purpose of this investigation was to describe the hand-specific complications of radiation therapy for patients with soft tissue sarcoma of the hand (STSH). METHODS: We performed a retrospective chart review of 55 consecutive patients with STSH treated by a single surgeon between 1993 and 2006. We identified 26 patients who were treated with external beam radiation, brachytherapy, or both, either preoperatively or postoperatively, and reviewed their clinical course. RESULTS: After a median follow-up of 7 years, 29 treatment-related complications occurred in 19 patients who had received radiation, whereas 3 of the 29 patients treated with surgery alone developed complications. All patients who received brachytherapy and 14 of the 21 treated with external beam radiation alone developed complications. There were 5 early minor, 2 early major, 3 late minor, and 19 late major complications. CONCLUSIONS: Patients with STSH who underwent radiation therapy had a high rate of complications. The complication rate in our series was higher in patients who had brachytherapy catheters placed adjacent to finger joints. A better understanding of predictors of complications will help to determine the optimal timing and type of radiation therapy to treat patients with STSH. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Tumors of the Hand and the Wrist.

Most tumors of the hand and the wrist are benign; however, malignant conditions can mimic benign tumors and must be worked up accordingly. Advanced imaging should be followed by biopsy before definitive treatment of tumors of unknown diagnosis. The most common soft-tissue masses in the hand and the wrist are ganglion cysts, whereas the most common bone tumors are enchondromas.

Functional Restoration Following Resection of Malignant Peripheral Nerve Sheath Tumour of the Median Nerve: A Case Report.

Management of malignant peripheral nerve sheath tumours (MPNSTs) is primarily surgical, involving surgical resection with wide margins, and frequently radiation therapy. When a MPNST involves a major peripheral nerve, wide resection leads to significant distal neurologic deficits. A patient who underwent resection of a MPNST involving the median nerve above the elbow is presented. Staged tendon and nerve transfers were performed to restore sensation to the thumb and index finger, thumb opposition and flexion, finger flexion and forearm pronation. These included: 1. radial sensory nerve branches to digital nerves of thumb and index finger, 2. ulnar nerve branch of flexor carpi ulnaris to pronator teres, 3. brachioradialis to flexor pollicis longus, 4. side-to-side transfer of flexor digitorum profundus tendon of index finger to middle, ring and little fingers, 5. extensor indicis proprius to abductor pollicis brevis. The rationale, approach, and favourable results of functional reconstruction in this patient are detailed.