Neuroma Analysis in Humans: Standardizing Sample Collection and Documentation.

INTRODUCTION: The biology of symptomatic neuromas is poorly understood, particularly the factors causing pain in human neuromas. Pain presence varies among and within individuals, with some having painful and nonpainful neuromas. To bridge these knowledge gaps, our group developed a protocol for assessing neuroma pain and collecting tissue for molecular analysis. This manuscript outlines our workflow and challenges and aims to inspire other centers to share their experiences with these tissues. METHODS: For every included patient and collected nerve or bone tissue specimens, we perform a detailed chart review and a multifaceted analysis of pain and pain perception immediately before surgery. We collect patient-reported outcome measures (PROMs) on pain, function, and mental well-being outcomes at preoperative assessment and at the 6-month follow-up postoperatively. Before surgery, the patient is assessed once again to obtain an immediate preoperative pain status and identify potential differences in pain intensity of different neuromas. Intraoperatively, specimens are obtained and their gross anatomical features are recorded, after which they are stored in paraformaldehyde or frozen for later sample analyses. Postoperatively, patients are contacted to obtain additional postoperative PROMs. RESULTS: A total of 220 specimens of nerve tissue have been successfully obtained from 83 limbs, comprising 95 specimens of neuromas and 125 specimens of nerves located proximal to the neuromas or from controls. CONCLUSIONS: Our approach outlines the methods combining specimen collection and examination, including both macroscopic and molecular biological features, with PROMs, encompassing physical and psychological aspects, along with clinical metadata obtained through clinical teams and chart review.

[Amputation neuroma with a difficult differential diagnosis from perihilar cholangiocarcinoma:a case report].

Biliary amputation neuroma is a rare benign tumor that develops due to the peribiliary dissection of nerve fibers during cholecystectomy, a common bile duct surgery, or lymph node dissection performed in gastric cancer surgery. We report a case of amputation neuroma that presented a challenging differential diagnosis from perihilar cholangiocarcinoma. A 64-year-old man, who had undergone open cholecystectomy 30 years ago, was incidentally found to have a bile duct tumor during computed tomography (CT) following surgery for renal cell carcinoma. He had no specific symptoms, and blood test results showed only a slight elevation in alkaline phosphatase levels. Contrast-enhanced CT revealed a 10-mm solid tumor with contrast effect in the common bile duct. On cholangiography, the tumor appeared as a protruding lesion with a smooth surface unilaterally. Given the atypical findings suggestive of cholangiocarcinoma, three bile duct biopsies were performed. Pathological examination did not rule out adenocarcinoma. The patient opted for surgery;however, an intraoperative rapid histological examination confirmed a benign disease, thereby avoiding extensive surgery. Consequently, a minimally invasive bile duct resection was performed. Postoperative histopathological examination revealed the tumor to be an amputation neuroma. Biliary amputation neuromas are characterized as unilateral protruding lesions with contrast effect or benign strictures. If such findings are observed in a patient with a history of surgery around the bile duct, the possibility of an amputation neuroma should be considered. However, completely ruling out malignancy preoperatively, even when suspecting amputation neuroma, can be challenging;therefore, considering surgery to achieve a definitive diagnosis is reasonable. During surgery, a rapid intraoperative histological examination is useful to avoid extensive procedures. In conclusion, diagnosing an amputation neuroma before surgery can be difficult, as it can mimic malignant tumors such as bile duct cancers. In this case, although a preoperative diagnosis of amputation neuroma was not feasible, performing a rapid intraoperative pathological examination helped avoid extensive surgery.

Epidemiology, risk factors, diagnosis, and treatment of intra-abdominal traumatic neuromas - a narrative review.

Traumatic neuroma (TN) is a disorganized proliferation of injured nerves arising from the axons and Schwann cells. Although TN rarely occurs in the abdominal cavity, the incidence of TN may be underestimated because of the large number of asymptomatic patients. TN can cause persistent pain, which seriously affects quality of life. TN of the biliary system can cause bile duct obstruction, leading to acute cholangitis. It is difficult to differentiate TN from malignancies or recurrence of malignancy, which results in a number of patients receiving aggressive treatment. We collected cases reports of intra-abdominal TN over the past 30 years form PubMed and cases diagnosed in our medical center over the past 20 years, which is the largest case series of intra-abdominal TN to the best of our knowledge. In this review, we discuss the epidemiology, pathophysiology, risk factors, classification, diagnosis, and management of intra-abdominal TN.

[Diagnostics and surgical treatment of painful neuromas]. / Diagnostik und chirurgische Therapie schmerzhafter Neurome.

BACKGROUND: Painful neuromas that often develop after peripheral nerve injury require adequate diagnosis and treatment because of the suffering they cause. The scientific basis for the development of painful neuromas has not yet been sufficiently investigated. In addition to conservative procedures, a larger number of surgical techniques are available for treatment of painful neuromas. OBJECTIVE: A review of the basic principles, diagnostic and treatment options for painful neuromas. MATERIAL AND METHODS: Presentation of the scientific basis regarding the development of painful neuromas. Illustration and discussion of the most common diagnostic and treatment procedures. RESULTS: The scientific basis regarding the development of painful neuromas after peripheral nerve injury has not yet been adequately developed. In order to be able to make a correct diagnosis, the use of standardized diagnostic criteria and adequate imaging techniques are recommended. In the sense of a paradigm shift, the use of the formerly neuroma-bearing nerve for reinnervation of target organs is to be preferred over mere burying in adjacent tissue. CONCLUSION: In addition to standardized diagnostics the management of painful neuromas often requires a surgical intervention after all conservative therapeutic measures have been exhausted. As an alternative to restoring the continuity of the injured nerve, targeted reinnervation of electively denervated target organs by the formerly neuroma-bearing nerve is preferable over other techniques.

Left Gluteal Maximus Neuroma Causing Long-Standing Gluteal Pain.

ABSTRACT: Diagnosing buttock pain is a challenge due to complex anatomy and multiple causes. Potential pathologies range from common and benign to rare and life-threatening. Common causes for buttock pain include referred pain from the lumbar spine and sacroiliac joint, hamstring origin tendinopathy, myofascial pain, ischiogluteal bursitis, gluteal pathology, and piriformis syndrome. Rarer causes include malignancy, bone infection, vascular anomalies, and spondyloarthropathies. Other conditions may be present concurrently in the lumbar and gluteal area, which can cloud the clinical picture. Correct diagnosis and early treatment may improve quality of life by providing a targetable reason for their distress, improving pain, and allowing the patient to get back to their activities of daily living. When treating a patient with buttock pain, it is essential to reevaluate the diagnosis when symptoms fail to improve despite appropriate intervention.Here, we discuss a case of a peripheral nerve sheath tumor found in the left gluteus medius muscle of a patient that caused persistent, debilitating buttock pain. After years of treatment for piriformis syndrome and possible spinous causes, the patient was ultimately diagnosed with a peripheral nerve sheath tumor through magnetic resonance imaging with contrast. Peripheral nerve sheath tumors are a diverse group of mostly benign tumors that can occur sporadically or associated with certain disease processes. These tumors usually present with pain, a soft tissue mass, or focal neurological deficits. Upon removal of the tumor, her gluteal pain completely resolved.

Trigeminal Traumatic Neuroma: a Comprehensive Review of the Literature Based On a Rare Case.

PURPOSE OF REVIEW: Traumatic neuromas in general, and trigeminal traumatic neuromas in particular, are relatively rare entities originating from a damage to a corresponding nerve or its branches. This manuscript is a comprehensive review of the literature on trigeminal traumatic neuromas based on an interesting and challenging case of bilateral intraoral lesions. RECENT FINDINGS: The diagnosis for this patient was bilateral trigeminal traumatic neuromas. It is possible that these patients have a genetic predisposition to the development of these lesions. It is a neuropathic pain condition and may mimic dental and other trigeminal pain entities. Topical treatment with lidocaine gel, utilizing a custom-made neurosensory stent, rendered the patient significant and sustained pain relief. Trigeminal traumatic neuromas present a diagnostic challenge even to a seasoned clinician, due to the complex clinical features that may mimic other entities. Topical medications such as local anesthetics may be a good viable alternative to systemic medications to manage the pain associated with the condition. Early identification of the lesion and the associated pain helps in the succinct management of symptomatic trigeminal traumatic neuromas.

The Management of Multiple Morton's Neuromas in the Same Foot: A Systematic Review.

The optimal treatment strategy for the presentation of multiple Morton's neuromas in adjacent intermetatarsal spaces of the same foot is yet to be determined. We aimed to summarize and assess the efficacy of current treatment strategies. A systematic review, adhering to PRIMSA guidelines was performed. A computer base search was completed in PubMed, Embase, Cinahl, ISI Web of Science, Scopus and Emcare, for articles reporting the treatment of multiple neuromas in the same foot. The review is registered in the international prospective register of systematic reviews (CRD42020213631). A total of 253 articles were identified, with 7 articles being included in the review. The most common treatment strategy reported was simultaneous neuroma excision using a single incision, while 2 studies each describe simultaneous excision with 2 separate incisions and delayed excision respectively. There is no strong evidence favoring use of delayed excision or multiple incisions. Further high-quality research is required to make more definitive conclusions and future research should investigate other strategies such as non-operative treatment.

[Traumatic Neuroma Mimicking Lymph Node Metastasis of Pancreatic Neuroendocrine Neoplasms Developed after Pancreatoduodenectomy-A Case Report].

A traumatic neuroma is a benign tumor consisting of a non-neoplastic growth of injured nerves as a result of trauma or surgery. It is rarely found in an abdominal cavity, but some reports showed that it occurred around the bile duct. We report a case of a 72-year-old man who underwent subtotal stomach-preserving pancreatoduodenectomy for pancreatic neuroendocrine neoplasms 4 years ago. An abdominal contrast-enhanced CT follow-up examination revealed a growing nodule on the dorsal surface of the portal vein. The lesion showed a mild increase in fluorodeoxyglucose uptake in FDG-PET⊘CT. A lymph node metastasis of pancreatic neuroendocrine neoplasms was suspected. Nodule resection was performed for purpose of diagnosis and treatment. The final pathological diagnosis was traumatic neuroma with no evidence of recurrence. Traumatic neuromas developed after pancreatoduodenectomy have not been reported. Postoperative masses around the bile ducts should also be considered traumatic neuromas.

Incidence, Diagnosis, and Management of Neuromas Following Radiofrequency Ablation Treatment: a Narrative Review.

OBJECTIVE: To determine the epidemiology of neuroma formation as a complication following radiofrequency ablation for chronic pain conditions as well as reviewing the diagnosis and management of neuromas. DESIGN: Evidence-based narrative review and critical appraisal of literature. RESULTS: A comprehensive review of the literature generated one case report describing neuroma formation following lumbar facet medial branch radiofrequency denervation. The rare incidence may be explained by neuroma pathophysiology and peripheral nerve injury produced by radiofrequency ablation, in combination with its asymptomatic nature. Diagnosis of neuromas is predominantly confirmed by clinical history and physical exam with potential for nerve blocks or imaging. Ultrasound has been suggested as a primary imaging modality with magnetic resonance imaging as a secondary option. Neuroma management ranges from conservative therapy to surgery with varying success rates. CONCLUSIONS: Neuroma formation following radiofrequency ablation procedures is exceedingly rare and could be a hypothetical concern in clinical practice. However, the true incidence may be inaccurate given the asymptomatic nature of neuromas.

To Be or Not to Be (A Morton's/Interdigital Neuroma): That Is the Question-A Case Series of Lateral Forefoot Pain Localized to the Proper Digital Nerve of the Fifth Toe.

ABSTRACT: We present 2 cases where the initial history and examination were similar to a Morton's/interdigital neuroma. In both cases, however, diagnostic ultrasound revealed symptomatic snapping of the proper digital nerve of the fifth toe. The anatomy of the proper digital nerve of the fifth toe may predispose it to a snapping phenomenon. Clinical awareness of this atypical cause of forefoot pain can help guide the diagnosis and treatment in those patients with persistent and refractory lateral forefoot pain and paresthesias.

Solitary circumscribed neuroma of the glans penis. An unusual finding.

Palisaded encapsulated neuroma is a rare, benign neural tumor. The involvement of the glans penis is rare; few cases have been reported. We present a 52-year-old man with a five-month course of a solitary painless lesion of the glans penis. Full excision of the nodule was performed. Histopathological and immunohistochemical analyses and examination was consistent with a palisaded encapsulated neuroma. We describe one of a few existing cases of this kind of tumor in the glans penis.

[A case of mass-forming chronic pancreatitis with amputation neuroma-like neurogenesis of the bile duct].

A man in his 40s visited a facility with the chief complaint of abdominal pain;liver dysfunction was detected, and consequently, he was referred to our hospital for further examinations. His medical history was unremarkable. He used to drink alcohol (beer, 1500mL) every day. Magnetic resonance imaging and computed tomography showed stenosis of the distal bile duct and slight dilation of the upstream bile duct. Common bile duct stones and gallbladder stones were not detected. Malignant tumors in the bile duct biopsy were not discovered. The patient underwent subtotal stomach preserving pancreatoduodenectomy. The pathological diagnosis was chronic pancreatitis with amputation neuroma-like neurogenesis of the bile duct.

Hypercellular Encapsulated Neuroma Imitating Desmoplastic Melanoma.

Palisaded encapsulated neuromas (PENs) are benign cutaneous nerve sheath proliferations that typically occur as flesh-colored papules solitarily on the head and neck in adults, with a slight predilection for females. Histopathologically, they are partially or completely encapsulated intradermal nodules with Schwann cells and axons in fascicles separated by clefts. Although these features are often characteristic, the hypercellular variant of PEN can pose a diagnostic challenge in distinguishing between other cellular neural and melanocytic lesions. We herein report a case of hypercellular PEN, which showed striking similarity to desmoplastic melanoma.

Diagnostic Criteria for Symptomatic Neuroma.

INTRODUCTION: After nerve injury, disorganized or incomplete nerve regeneration may result in a neuroma. The true incidence of symptomatic neuroma is unknown, and the diagnosis has traditionally been made based on patient history, symptoms, physical examination, and the anatomic location of pain, along with response to diagnostic injection. There are no formally accepted criteria for a diagnosis of neuroma. MATERIALS AND METHODS: A literature search was performed to identify articles related to neuroma: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and Pubmed, Embase, and the Cochrane Library were searched for all relevant articles pertaining to neuroma. Articles were screened by title and abstract for relevance. If an article was considered potentially relevant, the full article was reviewed. After consideration, 50 articles were included in this systematic review. RESULTS: No previous articles directly addressed diagnostic criteria for symptomatic neuroma. Factors related to neuroma diagnosis gleaned from previous studies include pain and cold intolerance (patient history), positive Tinel sign or diminished 2-point discrimination (physical examination findings), response to diagnostic nerve block, and presence of neuroma on diagnostic imaging (ultrasound or magnetic resonance imaging). Based on literature review, the importance and number of references, as well as clinical experience, we propose criteria for diagnosis of symptomatic neuroma. To receive a diagnosis of symptomatic neuroma, patients must have (1) pain with at least 3 qualifying "neuropathic" characteristics, (2) symptoms in a defined neural anatomic distribution, and (3) a history of a nerve injury or suspected nerve injury. In addition, patients must have at least 2 of the following 4 findings: (1) positive Tinel sign on examination at/along suspected nerve injury site, (2) tenderness/pain on examination at/along suspected nerve injury site, (3) positive response to a diagnostic local anesthetic injection, and (4) ultrasound or magnetic resonance imaging confirmation of neuroma. CONCLUSIONS: The diagnosis of neuroma is based on a careful history and physical examination and should rely on the proposed criteria for confirmation. These criteria will be helpful in more precisely defining the diagnosis for clinical and research purposes.

Painful Complications After Cosmetic Surgery: Management of Peripheral Nerve Injury.

BACKGROUND: Aesthetic procedures are among the most common surgeries performed by plastic surgeons. The prevalence of persistent pain remains unknown and underappreciated in the plastic surgery literature. OBJECTIVES: The purpose of this article was to increase awareness of this problem while describing the diagnostic and management strategies for patients with postoperative pain after aesthetic plastic surgery. METHODS: A literature review was performed utilizing the PubMed database to identify painful complications of brachioplasty, blepharoplasty, rhytidectomy, abdominoplasty, breast augmentation, mastopexy, and breast reduction. A treatment algorithm was described to guide plastic surgeons presented with patients reporting pain after aesthetic surgery. RESULTS: Title and abstract review followed by application of inclusion and exclusion criteria resulted in 20 clinical studies for this review, including lateral femoral cutaneous nerve, iliohypogastric nerve, and intercostal nerves after abdominoplasty; median antebrachial cutaneous nerve after brachioplasty; supraorbital, supratrochlear, and infratrochlear nerves after blepharoplasty; greater auricular nerve, auriculotemporal nerve, and zygomaticofacial nerve after rhytidectomy; and intercostobrachial nerve after breast surgery. CONCLUSIONS: Neuromas can be the source of pain following aesthetic surgery. The same clinical and diagnostic approach used for upper and lower extremity neuroma pain can be employed in patients with persistent pain after aesthetic surgery.

MEN 2B masquerading as chronic blepharitis and euryblepharon.

This is a retrospective case description of a single male patient found to have multiple endocrine neoplasia syndrome type 2B (MEN 2B). At the age of 14, he presented for evaluation of ocular irritation and eyelid thickening. Intraoperative assessment revealed mucosal lesions on the anterior dorsum of his tongue and biopsy of multiple eyelid lesions disclosed bilateral submucosal neuromas, leading to the diagnosis of MEN 2B. MEN 2B is a potentially life-threatening syndrome due to the risk of developing medullary thyroid carcinoma (MTC) and pheochromocytoma. The patient was found to have MTC requiring thyroidectomy. We hope to highlight the clinical and histopathologic findings of MEN 2B in an effort to emphasize the importance of its identification in the absence of a family history.

Bilateral Nonsynchronous Pacinian Corpuscle Neuroma.

Pacinian corpuscles are rapidly adapting mechanoreceptors distributed in the dermis of the fingers and palm of the hand. A neuroma of the pacinian corpuscle is rare and extremely painful, with only a few cases reported in the literature. A 71-year-old man with pain and swelling on his left index finger, initially diagnosed as tenosynovitis resistant to nonsurgical treatment, was referred to our center. During surgery, a cluster of spherical, gray lesions close to the digital nerve was found and excised. The pathological diagnosis was neuroma of the pacinian corpuscles. Two years later, he reported the same clinical findings on his right index finger with no improvement after nonsurgical treatment. During surgery, the same lesions were found and also identified as pacinian corpuscle neuromas.

Injury to the perineal branch of the pudendal nerve in men: Outcomes from surgical resection of the perineal branches.

OBJECTIVE: The objective is to report the outcome of an anterior surgical approach to treat neuroma of the perineal branch of the pudendal nerve (PBPN). PATIENTS AND METHODS: An IRB-approved prospective study enrolled 14 consecutive male patients from 2011 through 2015 who had symptoms of perineal/scrotal pain. Each patient had a successful, diagnostic, pudendal nerve block. The surgical procedure was resection of the PBPN and implantation of the nerve into the obturator internus muscle. Mean age at surgery was 50 ± 15 years. Median duration of pain symptoms was 5.5 years (range 1.2-42.9 years). Mechanisms of injury was exercise (6/14), prostatectomy (4/14), and falls (4/14). Outcomes were the Male Pudendal Pain Functional Questionnaire (MQ), and the Numeric Pain Rating Scale (NPRS). RESULTS: The mean postoperative follow-up was 26 ± 14 months. The MQ demonstrated that after surgery, patients overall had significantly less disability due to pudendal pain (P < .03). The NPRS revealed that pain significantly improved (P < .004). CONCLUSIONS: Resection of the PBPN and implantation of this nerve into the obturator internus muscle significantly relieved men's pelvic pain disability.

Nerve Transfer With Entubulated Nerve Allograft Transfers to Treat Recalcitrant Lower Extremity Neuromas.

Neuroma formation in the lower extremity can be debilitating to patients, especially when the neuromas are recurrent. The results of an advanced nerve reconstruction technique consisting of nerve transfer combined with nerve allograft and entubulation was evaluated in 4 patients with severe, debilitating, lower extremity neuromas. At a mean follow-up period of 26 months, the mean visual analog scale had improved from 9.5 preoperatively to 1.25 postoperatively (p < .05). These data suggest that techniques using a nerve allograft with a nerve conduit could be of great assistance in successfully managing debilitating neuromas of the lower extremity. Thus, further in-depth evaluation of these techniques is warranted.

SOS1 frameshift mutations cause pure mucosal neuroma syndrome, a clinical phenotype distinct from multiple endocrine neoplasia type 2B.

BACKGROUND: Mucosal neuromas, thickened corneal nerves and marfanoid body habitus are characteristic phenotypic features of multiple endocrine neoplasia type 2B (MEN2B) and often provide an early clue to the diagnosis of the syndrome. Rarely, patients present with typical physical features of MEN2B but without associated endocrinopathies (medullary thyroid carcinoma or pheochromocytoma) or a RET gene mutation; this clinical presentation is thought to represent a distinct condition termed 'pure mucosal neuroma syndrome'. METHODS: Exome sequencing was performed in two unrelated probands with mucosal neuromas, thickened corneal nerves and marfanoid body habitus, but no MEN2B-associated endocrinopathy or RET gene mutation. Sanger sequencing was performed to confirm mutations detected by exome sequencing and to test in family members and 3 additional unrelated index patients with mucosal neuromas or thickened corneal nerves. RESULTS: A heterozygous SOS1 gene frameshift mutation (c.3266dup or c.3248dup) was identified in each proband. Sanger sequencing showed that proband 1 inherited the c.3266dup mutation from his affected mother, while the c.3248dup mutation had arisen de novo in proband 2. Sanger sequencing also identified one further novel SOS1 mutation (c.3254dup) in one of the 3 additional index patients. CONCLUSION: Our results demonstrate the existence of pure mucosal neuroma syndrome as a clinical entity distinct from MEN2B that can now be diagnosed by genetic testing.