A Subungual Nevoid Melanoma of the Right Hallux from a 65-Year-Old Man: A Case Report.

Nevoid melanoma (NeM) is a rare variant of malignant melanoma characterized by slight cellular atypia, polymorphism, and incomplete maturation. It most frequently occurs on the trunk and arms but rarely on the foot. Here, we report a subungual NeM of the right hallux. A 65-year-old man presented with severe pain of 6 months' duration to his right great toe following self-treatment for an ingrown nail. He was evaluated and treated with debridement of the toenail at an urgent medical center 3 months prior. However, this had not relieved his pain. The patient also noticed discoloration of his distal great toe over the past 3 months. Removal of part of the ingrown nail revealed a pigmented mass extending distally from the matrix. Surgical excision of the mass was performed because of the concern for malignancy. The diagnosis of NeM was based on histologic analysis along with enhanced diagnostic modalities. The patient was further treated with surgical amputation of the great toe and anti-programmed cell death-1 therapy. The patient had no relapse at 1-year follow-up. Nevoid melanoma is a rare variant of malignant melanoma on the toes, which needs to be differentiated from a nevus with atypia, with a variety of modalities including cellular and molecular profiling. The optimal treatment is amputation.

Periungual Amelanocytic Malignant Melanoma with Osteocartilaginous Differentiation of the Right Hallux: A Case Report.

Malignant melanoma with osteocartilaginous differentiation is extremely rare. We report a case of periungual osteocartilaginous melanoma (OCM) on the right hallux. A 59-year-old man presented with a rapidly growing mass with drainage on his right great toe after treatment of ingrown toenail and infection 3 months earlier. Physical examination showed a 2.0×1.5×1.0-cm, malodorous, erythematous, dusky, granuloma-like mass along the fibular border of the right hallux. Pathologic evaluation of the excisional biopsy revealed diffuse epithelioid and chondroblastoma-like melanocytes with atypia and pleomorphism in the dermis with strong SOX10 immunostaining. The lesion was diagnosed as osteocartilaginous melanoma. The patient was referred to a surgical oncologist for further treatment. Osteocartilaginous melanoma is a rare variant of malignant melanoma that needs to be differentiated from chondroblastoma and other lesions. Immunostains for SOX10, H3K36M, and SATB2 are helpful for the differential diagnosis.

Phosphaturic Mesenchymal Tumor Along the Hallux side Inducing a Chronic non-Healing Wound: A Case Report with Literature Review.

Phosphaturic mesenchymal tumor (PMT) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia, and bone calcification disorders. Complete surgical resection of the tumor is believed to be the most effective treatment measure. However, the diagnosis of PMT is very difficult because of its insidious and small size, especially, when it appears in subcutaneous tissue with a chronic non-healing wound. We report a rare case of a 38-year-old man with a chronic non-healing wound on the left hallux for approximately eight months. Plain radiographic images and magnetic resonance imaging (MRI) revealed a cystic radiolucent shadow in the left distal phalanx. Bone scan observations also showed increased uptake in the same location. Histologically, this tumor was composed of numerous spindle cells with clusters of giant cells. The serum FGF23 level was significantly higher before surgery, with higher FGF23 levels closer to the tumor. Reverse transcription polymerase chain reaction and immunohistochemistry further confirmed the high expression of FGF23 in tumors. These data suggest that FGF23 may be a potential causative factor of PMT. The serum FGF23 levels might be useful for the diagnosis of PMT and localization of the tumor. The tumor was CD56- and D2 to 40-positive and CD31-negative. The non-healing wound caused by PMT might be attributed to the invasive growth of the tumor, destruction of intercellular junctions, and decrease in the number of endothelial cells.

Refractory satellite ganglion cyst in the hallux and finger.

Painful ganglion cysts that develop in the hallux and finger usually enlarge progressively to the peripheral direction. Simple resection of satellite ganglion cyst alone has been reported to cause a high rate of recurrence and treatment is often very difficult. The purpose of this study is to evaluate the appropriate surgical treatment for painful satellite ganglion cysts in the hallux and finger and discuss the origin of the ganglion cysts in cases treated surgically at our hospital. We reviewed five cases (three males and two females, ages 55-87 years), three of which occurred in the hallux and two in the finger. In all cases, the preoperative magnetic resonance image showed a large fluid of the flexor tendon sheath. And also, joint effusion was found in the metatarsophalangeal joint and the proximal interphalangeal joint. The first case of the hallux ganglion underwent simple excision of the cyst and had recurrences three times. In the other four cases, the additional synovectomy of the metatarsophalangeal joint and the proximal interphalangeal joint was performed along with ganglion cyst excision. These cases had no recurrence up to 1 year after operation. Recently, there have been reports that tendon sheath ganglions are connected to the ankle, wrist, hallux, and phalangeal joints. Although there are a few cases in our department, satellite ganglion cyst of the hallux and finger possibly originates from adjacent joints. Additional synovectomy of the affected joint should be performed for the excision of satellite ganglion cyst to prevent recurrence.

What Is the Efficacy of a Nonoperative Program Including a Specific Stretching Protocol for Flexor Hallucis Longus Tendonitis?

BACKGROUND: Diagnosis and treatment of tendonitis/entrapment of the flexor hallucis longus (FHL) has been sporadically described in the evidence, primarily in the context of dancers and other athletes. Although various nonspecific nonoperative treatments have been described, it is not clear how often they achieve a satisfactory amount of symptom improvement. QUESTIONS/PURPOSES: The present study was designed to address the following questions regarding the nonoperative treatment of FHL tendonitis: (1) In a population of patients where the default management option for FHL tendonitis is a comprehensive nonsurgical approach, what proportion of patients thus treated opted not to have surgery? (2) What factors were associated with a patient's decision to undergo surgery after a period of nonsurgical management? METHODS: The 656 patients included were all those diagnosed with FHL tendonitis who were initially treated nonoperatively in the foot and ankle division between January 2009 and December 2018. Demographics, comorbidities, examination findings, imaging results, pain scores, treatment instituted, and final outcome were obtained from the electronic medical record. The primary outcome was the decision to have surgery due to unsatisfactory symptom improvement. We compared patients who opted for surgery with those who did not after nonoperative treatment with univariable and multivariable statistics using demographics, comorbidities, and clinical findings as potential risk factors, with p < 0.05. RESULTS: Forty-four percent (180 of 409) of patients decided to forgo surgery after the institution of a specific FHL stretching program. Surgery was more likely in patients with clinical hallux rigidus (OR 2.4 [95% CI 1.16 to 4.97]; p = 0.02) or posteromedial ankle pain (OR 1.78 [95% CI 1.12 to 2.83]; p = 0.01) and less likely in those who completed an FHL stretching program (OR 0.15 [95% CI 0.08 to 0.27]; p < 0.001). CONCLUSION: FHL tendonitis is more common than the previous evidence suggests and frequently occurs in nonathletes. Once it was diagnosed by detection of tenderness anywhere along the tendon, most frequently at the fibroosseous tunnel, nonoperative treatment focused on specific FHL stretching and immobilization in more severe cases reduced the symptoms to the extent that 44% of patients decided that surgery was unnecessary. The key to its diagnosis is awareness that this injury is possible because most patients treated in this study had been previously seen by orthopaedic providers who had not appreciated the presence of the condition, leading to a delay in diagnosis and treatment of more than a year in many patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K+ channelopathies.

Decreased or increased activity of potassium channels caused by loss-of-function and gain-of-function (GOF) variants in the corresponding genes, respectively, underlies a broad spectrum of human disorders affecting the central nervous system, heart, kidney, and other organs. While the association of epilepsy and intellectual disability (ID) with variants affecting function in genes encoding potassium channels is well known, GOF missense variants in K+ channel encoding genes in individuals with syndromic developmental disorders have only recently been recognized. These syndromic phenotypes include Zimmermann-Laband and Temple-Baraitser syndromes, caused by dominant variants in KCNH1, FHEIG syndrome due to dominant variants in KCNK4, and the clinical picture associated with dominant variants in KCNN3. Here we review the presentation of these individuals, including five newly reported with variants in KCNH1 and three additional individuals with KCNN3 variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant KCNN3, KCNH1, and KCNK4 variants, sharing developmental delay and/or ID, coarse facial features, gingival enlargement, distal digital hypoplasia, and hypertrichosis. We suggest to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K+ conductance, referred to as syndromic neurodevelopmental K+ channelopathies due to dominant variants in KCNH1, KCNK4, or KCNN3.

Treatment of Giant Cell Tumor of Soft Tissue Disguised as Giant Cell Tumor of the Bone Involving the Distal and Proximal Phalanges of the Great Toe.

Giant cell tumors are benign tumors that are locally aggressive and rare in the foot. Giant cell tumors involving bone in the foot have an incidence of 1.2% to 2.8%, whereas giant cell tumors of the tendon sheath constitute 3% to 5% of all giant cell tumors in the foot and ankle. We present a case of giant cell tumor of the soft tissue disguised as a giant cell tumor of bone in a healthy 29-year-old male patient. Through radiographic and magnetic resonance imaging evaluation, it was determined that this patient had a bone tumor invading the distal and proximal phalanges of his left great toe with the involvement of soft tissue. With the use of the evidence-based medicine and patient expectation, the decision was made to amputate the digit. To much surprise, when the histopathologic results were reviewed, it was determined that the excised lesion was consistent with giant cell tumor of soft tissue that did not involve the bone.

Eumycetoma, A Neglected Tropical Disease in the United States.

Eumycetoma, caused by fungi, is a neglected tropical disease. It is endemic in the "mycetoma belt" countries but rare in North America. We report a case of pedal eumycetoma in the state of Maryland. A 51-year-old male immigrant from Guatemala presented with multiple, enlarging nodules on the dorsal surface of his left great toe present for 1 year, and a new one in the left arch area present for 6 months. The nodular lesions were surgically excised in two separate operations. Pathologic evaluation of all nodules revealed eumycetomas characterized by the Splendore-Hoeppli phenomenon, showing an amorphous eosinophilic center filled with numerous fungal hyphae, observed on periodic acid-Schiff-stained slides, with a surrounding cuff of neutrophils. Polymerase chain reaction-based sequencing identified Cladosporium cladosporioides in the tissues. The patient was further treated with oral fluconazole for 2 months. The patient recovered well postoperatively and had no recurrence at 20-month follow-up. In conclusion, even though eumycetoma is regarded as a rare disease in North America, its incidence may be higher than reported because of millions of immigrants from endemic regions in the United States, which highlights the need to raise awareness of this devastating disease in the medical community. Eumycetoma needs to be differentiated from other infectious and noninfectious benign and malignant lesions. Optimal treatment includes surgical excision with antifungal therapy.

Subungual Exostosis on the Right Hallux.

Subungual exostosis (SE) is a benign, relatively uncommon bony growth underneath the nails of the distal phalanx of toes or fingers, with a majority on the toes. Clinically, it has two subvariants-protruded and nonprotruded growths from nail plates-which are treated differently. In this article, we report a case of protruded SE in a teenager with illustrative surgical excision. A 15-year-old boy presented with a painful growth on his right great toe of 6 months' duration. Physical examination revealed a 1-cm-diameter, solid, erythematous, rough, irregular growth penetrating through the skin along the dorsolateral nail bed of the right hallux with deformity of the lateral nail plate. Radiographs showed an elevated mass over the distal phalanx of the right lateral hallux. The mass was surgically excised and histopathologic examination confirmed the diagnosis of SE. The patient had no relapse or recurrence at follow-ups of 6 and 18 months. Subungual exostosis is a relatively uncommon bony growth in the toes. Radiography is favored for the diagnosis. Complete surgical excision is the optimal treatment, with rare recurrence. It needs to be differentiated from other bony lesions, including bizarre parosteal osteochondromatous proliferation, myositis ossificans, fibro-osseous pseudotumor, osteochondroma, and enchondroma.

Temple syndrome and Kagami-Ogata syndrome: clinical presentations, genotypes, models and mechanisms.

Temple syndrome (TS) and Kagami-Ogata syndrome (KOS) are imprinting disorders caused by absence or overexpression of genes within a single imprinted cluster on human chromosome 14q32. TS most frequently arises from maternal UPD14 or epimutations/deletions on the paternal chromosome, whereas KOS most frequently arises from paternal UPD14 or epimutations/deletions on the maternal chromosome. In this review, we describe the clinical symptoms and genetic/epigenetic features of this imprinted region. The locus encompasses paternally expressed protein-coding genes (DLK1, RTL1 and DIO3) and maternally expressed lncRNAs (MEG3/GTL2, RTL1as and MEG8), as well as numerous miRNAs and snoRNAs. Control of expression is complex, with three differentially methylated regions regulating germline, placental and tissue-specific transcription. The strong conserved synteny between mouse chromosome 12aF1 and human chromosome 14q32 has enabled the use of mouse models to elucidate imprinting mechanisms and decipher the contribution of genes to the symptoms of TS and KOS. In this review, we describe relevant mouse models and highlight their value to better inform treatment options for long-term management of TS and KOS patients.

"Electrifying dysmorphology": Potassium channelopathies causing dysmorphic syndromes.

Potassium channels are a heterogeneous group of membrane-bound proteins, whose functions support a diverse range of biological processes. Genetic disorders arising from mutations in potassium channels are classically recognized by symptoms arising from acute channel dysfunction, such as periodic paralysis, ataxia, seizures, or cardiac conduction abnormalities, often in a patient with otherwise normal examination findings. In this chapter, we review a distinct subgroup of rare potassium channelopathies whose presentations are instead suggestive of a developmental disorder, with features including intellectual disability, craniofacial dysmorphism or other physical anomalies. Known conditions within this subgroup are: Andersen-Tawil syndrome, Birk-Barel syndrome, Cantú syndrome, Keppen-Lubinsky syndrome, Temple-Baraitser syndrome, Zimmerman-Laband syndrome and a very similar disorder called Bauer-Tartaglia or FHEIG syndrome. Ion channelopathies are unlikely to be routinely considered in the differential diagnosis of children presenting with developmental concerns, and so detailed description and photographs of the clinical phenotype are provided to aid recognition. For several of these disorders, functional characterization of the genetic mutations responsible has led to identification of candidate therapies, including drugs already commonly used for other indications, which adds further impetus to their prompt recognition. Together, these cases illustrate the potential for mechanistic insights gained from genetic diagnosis to drive translational work toward targeted, disease-modifying therapies for rare disorders.

A Review of the Phenotype of Synpolydactyly Type 1 in Homozygous Patients: Defining the Relatively Long and Medially Deviated Big Toe with/without Cupping of the Forefoot as a Pathognomonic Feature in the Phenotype.

Synpolydactyly type 1 (SPD1, OMIM 186000) is inherited as autosomal dominant and is caused by HOXD13 mutations. The condition is rare and is known for its phenotypic heterogeneity. In the homozygous state, the phenotype is generally more severe and is characterized by three main features: a more severe degree of syndactyly, a more severe degree of brachydactyly, and the frequent loss of the normal tubular shape of the metacarpals/metatarsals. Due to the phenotypic heterogeneity and the phenotypic overlap with other types of syndactyly, no pathognomonic feature has been described for the homozygous phenotype of SPD1. In the current communication, the author reviews the literature on the phenotypes of SPD1 in homozygous patients. The review documents that not all homozygous patients show a severe hand phenotype. The review also defines the "relatively long and medially deviated big toe with/without cupping of the forefoot" as a pathognomonic feature in the phenotype. Illustration of this feature is done through a demonstrative clinical report in a multigeneration family with SPD1 and HOXD13 polyalanine repeat expansion. Finally, the pathogenesis of the clinical features is reviewed.

Ulcer metastasis? Anatomical locations of recurrence for patients in diabetic foot remission.

BACKGROUND: The "cancer analogy" is powerful for communicating risk to and organizing care for patients with diabetic foot syndrome. One potentially underappreciated similarity between cancer and foot ulcers is that both can recur at anatomical locations distinct from the primary occurrence, albeit with different physiological mechanisms. Few studies have characterized the location of diabetic foot ulcer recurrence, and these have been limited by considering only the first recurrent wound following a recent-healed wound. We therefore characterized the anatomical locations at which diabetic foot ulcers are likely to recur considering multiple wounds during follow-up and the locations of all prior wounds documented in the participant's history. METHODS: We completed a secondary analysis of existing data from a 129 participant multi-center study of participants in diabetic foot remission. The primary outcome was plantar foot ulceration, and each participant was followed for 34 weeks or until withdrawing consent, allowing characterization of all wounds occurring. We stratified the anatomical locations of wounds prior to the trial by the following outcome categories during the trial: no recurrence, recurrence to the same anatomical location, recurrence to a different anatomical location on the same foot, and recurrence to the contralateral foot. RESULTS: A large percentage (48%) of wounds recurred to the contralateral foot, and the proportion of subsequent foot ulcer to the contralateral limb was largely unaffected by the anatomical location of foot ulcer prior to the study. Only 17% of prior diabetic foot ulcers were followed by recurrence to the same anatomical location. Rates of recurrence remained high during treatment of a wound (0.41 foot ulcer/ulcer-year). Participants had documented wounds to 2.2 distinct anatomical locations on average, and more than 60% of participants had wounds to more than one plantar location by the end of the study. CONCLUSIONS: Given the significant morbidity, mortality, and resource utilization associated with foot ulcer recidivism, quality and evidenced-based preventive care is essential. Our results better characterize the burden of recurrence and to what anatomy recurrence is most likely. These insights may benefit providers and patients alike for the provision of high-quality preventive care thereby resulting in reduced morbidity, mortality, and cost. TRIAL REGISTRATION: The study providing the data for this secondary analysis was registered on ClinicalTrials.gov (NCT02647346) on January 6, 2016. The study was retrospectively registered.

Sex differences in the patterning of age-related bone loss in the human hallucal metatarsal in rural and urban populations.

OBJECTIVES: Age-degenerative features of the metatarsals are poorly known despite the importance of metatarsal bone properties for investigating mobility patterns. We assessed the role of habitual activity in shaping the patterning and magnitude of sexual dimorphism in age-related bone loss in the hallucal metatarsal. MATERIALS AND METHODS: Cross-sections were extracted at midshaft from micro-computed tomography scan models of individuals from medieval rural (Abingdon Vineyard) and early industrial urban (Spitalfields) settings (n = 71). A suite of cross-sectional geometry dimensions and biomechanical properties were compared between populations. RESULTS: The rural group display generally stronger and larger metatarsals that show a greater capacity to resist torsion and that have comparatively greater bending strength along the medio-lateral plane. Men in both groups show greater values of cortical area than women, but only in the urban group do men show lower magnitudes of age-related decline compared to females. Women in rural and urban populations show different patterns of age-related decline in bone mass, particularly old women in the urban group show a marked decline in cortical area that is absent for women in the rural group. DISCUSSION: Lifetime exposure to hard, physical activity in an agricultural setting has contributed to the attainment of greater bone mass and stronger bones in young adults. Furthermore, over the life-course, less of this greater amount of bone is lost, such that sustained activity levels may have acted to buffer against age-related decline, and this is most pronounced for women, who are expected to experience greater bone loss later in life than men.

Intraosseous Tophaceous Gout in Hallux Mimicking a Bone Tumor in a Young Patient: A Case Report.

CASE: A 17-year-old man experienced night pain in his right hallux. Radiographs revealed a lytic lesion in the proximal phalanx of the right hallux. Magnetic resonance imaging showed a low-signal intensity mass on T1-weighted sequences and isointense-high-signal intensity on T2-weighted sequences. We suspected a benign bone tumor such as osteoid osteoma or a bone cyst and consequently performed biopsy and surgical treatment. The lesion was filled with a whitish chalk-like substance, and pathologic examination revealed tophaceous gout. CONCLUSIONS: It can be difficult to distinguish intraosseous tophaceous gout from other diseases, including bone tumors, using imaging; hence, pathological examination may be necessary for the diagnosis.