Multiple Endocrine Neoplasia Type 2B Research Articles

S2080 Mucosal Schwann Cell Hamartoma of the Sigmoid Colon in a Transgender Female to Male on Testosterone Therapy: A Case Report

Introduction: Mucosal Schwann cell hamartomas of the gastrointestinal tract are rare benign mesenchymal neoplasms, of which the exact incidence within the population is unknown. First described as a new entity in 2009 by Gibson and Hornick1 in a retrospective case study examining pathology from 26 patients, it is suspected that the increase in incidence of colonic mucosal Schwann cell hamartomas is due to the increase of colorectal cancer screening. As of 2020, there have been 41 documented cases of Schwann cell hamartomas.2 Case Description/Methods: A 63-year-old transgender female to male on testosterone therapy for 10 years and history of adenomatous colon polyps 3 years prior presented for outpatient surveillance colonoscopy. The patient had no personal or family history of neurofibromatosis type 1 (NF1), Cowden syndrome, or multiple endocrine neoplasia (MEN) type 2b. Colonoscopy was notable for a 1 mm sessile polyp in the sigmoid colon (Figure 1) and 4 mm sessile ascending colon polyp. Review of the pathology demonstrated a tubular adenoma without dysplasia in the ascending colon, and in the sigmoid colon S-100 positive spindle cells with elongated nuclei and dense eosinophilic cytoplasm, consistent with a mucosal Schwann cell hamartoma (Figures 2 and 3). Discussion: Our patient presented for routine surveillance colonoscopy and was found to have a rare benign mesenchymal neoplasm of the sigmoid colon, a Schwann cell hamartoma. Mucosal Schwann cell hamartomas are typically small, 1-8 mm, primarily located in the left colon, have a female predominance and an average age at presentation of 62.3 They are not associated with malignancy or inherited syndromes.1,4 The histological differential diagnosis includes schwannoma, neurofibroma, mucosal neuroma, ganglioneuroma, ganglioneurmatosis, perineurioma and GIST, making accurate diagnosis key to avoid unnecessary treatments.4 Interestingly, our patient found to have a mucosal Schwann cell hamartoma of the sigmoid colon is a transgender female to male on testosterone therapy, which to our knowledge has not previously been reported. Recent studies in animal models have suggested testosterone may promote the growth of colorectal adenomas.5 The role of sex hormones in development of these neoplasms has yet to be explored.Figure 1.: Endoscopic finding of a 1 mm sigmoid colon polyp.Figure 2.: Histologic features show spindle cell proliferation, elongated nuclei, and eosinophilic cytoplasm under hematoxylin and eosin-stained sigmoid colonic mucosa. This is consistent with a mucosal Schwann cell hamartoma.Figure 3.: Immunochemistry for S-100 spindle cells within the sigmoid colon. This stain further solidified the diagnosis of Schwann cell hamartoma.

Successful treatment of mucosal neuromas by radiofrequency ablation in a patient with multiple endocrine neoplasia type 2B.

This is the first report of mucosal neuromas being treated successfully with radiofrequency ablation in a patient with multiple endocrine neoplasia type 2B.

Fracture Risk in Pediatric Patients With MEN2B.

The skeletal phenotype of patients with MEN2B has been described but fracture risk in these patients has not yet been evaluated. This work aims to better delineate fracture risk in patients with multiple endocrine neoplasia type 2B (MEN2B). This case series with chart review was conducted at the National Institutes of Health, Pediatric Oncology Branch. A total of 48 patients with MEN2B were identified, with an age range of 5 to 36 years, median of 19; 24 of 48 (50%) patients were female. Medical records, demographic information, available imaging, and laboratory results were reviewed. History up to age 19 was included in the statistical analyses. Of the 48 patients with MEN2B, 20 patients experienced at least one fracture. The majority (n = 18) experienced their first fracture at or before age 19. The observed frequency of fracture occurrence throughout childhood (0-19 years) was 38%, with very little difference between males and females. This frequency is higher than the 9.47 to 36.1 fractures per 1000 persons per year that has been reported in healthy pediatric cohorts in the United States. Less common sites of fracture including vertebral compression fracture and pelvic fractures were observed in patients with MEN2B. In this group of patients with MEN2B, there was an increased overall risk of fracture compared to general pediatric cohorts in the United States. Less common sites of fracture were also observed. This suggests a possible effect of an activating RET mutation on bone physiology and warrants further investigation.

Withdrawn: Successful treatment of mucosal neuromas by radiofrequency ablation in a patient with multiple endocrine neoplasia type 2B.

Luis Escalante, Jennyfer Granizo-Rubior,Esteban Ortiz-Prado, Víctor Pinos-León, Astrid Maldonado,David Chandler.1 Successful treatment of mucosal neuromas by radiofrequency ablation in a patient with multiple endocrine neoplasia type 2B. https://doi.org/10.1002/ski2.109 The above article from the Skin Health Disease published online on 28 July 2022 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1002/ski2.109) has been withdrawn by agreement among the authors, the Journal Editor-in-Chief George Millington and John Wiley & Sons Inc., Ltd on behalf of the British Association of Dermatology. The withdrawal has been agreed because the article was accepted and published online due to publisher error. This manuscript has been resubmitted and accepted as a Review Article and will publish with a new doi, https://doi.org/10.1002/ski2.146.

Case Report of Rare Hereditary Endocrine Cancer Syndrome: Multiple Endocrine Neoplasia Type 2B

Case Report of Rare Hereditary Endocrine Cancer Syndrome: Multiple Endocrine Neoplasia Type 2B

Amphicrine Medullary Thyroid Carcinoma - a Case-Based Review Expanding on Its MUC Expression Profile.

Amphicrine phenotype in medullary thyroid carcinoma (MTC) is a rare phenomenon characterized by tumor cells that show both endocrine differentiation (calcitonin secretion) and exocrine differentiation (mucin production and secretion). Not much is known about the pathobiology of amphicrine MTCs. This report undertook a case-based review approach by discussing the cytological, histopathological, and ultrastructural features of this rare enigmatic entity, expanding on the radiological and novel MUC immunohistochemistry findings from a 28-year-old MEN2B syndrome patient with C cell hyperplasia and multifocal MTC with amphicrine features. The patient had widespread hematogenous metastases at presentation. MUC immunoexpression analysis revealed evidence of micro-lumina formation, and unique to-date unreported expression patterns of MUC1, MUC5AC, and MUC6 in an amphicrine subtype of MTC. Review of the literature identified five other MTC cases with well-documented amphicrine features. Of these six cases, two were associated with MEN2B syndrome, and four had metastatic disease. Follow-up was available in three patients, and two died of disease. Recognition of this rare subtype of MTC may be of clinical interest given their frequent link to MEN2B syndrome and biological aggressiveness.

Young woman with Multiple Endocrine Neoplasia 2B (MEN 2B) Diagnosed by PET-CT-A Case Report

Multiple endocrine neoplasia, type 2B (MEN2B) is an autosomal dominant syndrome characterized by medullary thyroid carcinoma, pheochromocytoma, multiple mucosal neuromas & intestinal ganglioneuromas. A young woman of 20 years presented with irregularity of both lips since childhood and a midline neck swelling which gradually increased in size within last 1 year. She had hypertension and history of three episodes of paroxysmal spells characterized by headache, palpitations and excessive sweating during past 5 months. On physical examination, patient was having tachycardia, high blood pressure level (140/100 mmHg), sweaty with no tremor or exophthalmos. She had bumpy lips, multiple mucosal neuromas in lip & buccal mucosae, a hard nodular goiter and no marfanoid habitus. Core biopsy from right thyroid lobe revealed medullary thyroid carcinoma. Calcitonin level were markedly elevated. 18F-FDG PET-CT scan showed heterogeneous mixed density soft tissue mass involving both lobes and isthmus of thyroid gland with intense FDG uptake and FDG avid enlarged right cervical lymph nodes. A well circumscribed complex mass was found in the left upper abdomen adjacent to pancreas. Left adrenal gland showed a heterogeneous mass with mild FDG uptake and according to PET-CT findings, patient was diagnosed as a case of MEN 2B. Bangladesh J. Nuclear Med. 24(1&2): 60-63, 2021

Patient with pregnancy and possible MEN 2b syndrome: case report

Patient with pregnancy and possible MEN 2b syndrome: case report

V13-10 LINEAR STAPLING DEVICE IN LAPAROSCOPIC PARTIAL ADRENALECTOMY FOR PHEOCHROMOCYTOMA IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 2B

You have accessJournal of UrologyCME1 May 2022V13-10 LINEAR STAPLING DEVICE IN LAPAROSCOPIC PARTIAL ADRENALECTOMY FOR PHEOCHROMOCYTOMA IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 2B Patricio Garcia Marchiñena, Andrés Germán Alfieri, Facundo Barbagallo, Ricardo Hosman Basto, and Alberto Jurado Patricio Garcia MarchiñenaPatricio Garcia Marchiñena More articles by this author , Andrés Germán AlfieriAndrés Germán Alfieri More articles by this author , Facundo BarbagalloFacundo Barbagallo More articles by this author , Ricardo Hosman BastoRicardo Hosman Basto More articles by this author , and Alberto JuradoAlberto Jurado More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002646.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Solitary adrenal glands, bilateral adrenal tumors or hereditary syndromes are indications of partial adrenalectomy to avoid the need for lifelong corticosteroid replacement. Laparoscopic partial adrenalectomy (LPA) is a safe and effective method in order to provide complete removal of small adrenal lesions, as well as preservation of normal glandular parenchyma. Our objective is to describe a LPA using a linear stapling device in a hereditary pheochromocytoma. METHODS: We present the case of a 29-year-old male with hypertension, anxiety and heart palpitations due to pheochromocytoma caused by multiple endocrine neoplasia type 2B. Urinary catecholamine levels were four times higher than normal. CT scan revealed a 33 mm hypermetabolic right adrenal mass. Transperitoneal LPA was performed with the patient in left lateral decubitus. Four trocars were placed as the described technique parallel to the costal line. Right adrenal tumor was resected using a vascular linear stapling device. To preserve the blood supply of the remnant adrenal gland, it was not extensively dissected and the main adrenal vein was totally preserved. RESULTS: The patient had uneventful postoperative recovery. Surgical time was 90 minutes. Patient was discharged on the 2nd day. Pathology confirmed a 3.5 cm benign composite pheochromocytoma-ganglioneuroma with negative surgical margins. After surgery the patient achieved a complete clinical and biochemical response. During a follow-up of 6 months, no biochemical or radiological recurrence was observed. CONCLUSIONS: LPA using a linear stapling device is a valid alternative to total adrenalectomy when normal adrenal tissue has to be preserved. Source of Funding: No source of fundings © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1034 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Patricio Garcia Marchiñena More articles by this author Andrés Germán Alfieri More articles by this author Facundo Barbagallo More articles by this author Ricardo Hosman Basto More articles by this author Alberto Jurado More articles by this author Expand All Advertisement PDF DownloadLoading ...

Agresivni klinički tok medularnog mikrokarcinoma štitaste žlezde

Medullary thyroid carcinoma is a form of neuroendocrine tumor that arises from parafollicular C cells which produce calcitonin. In addition to calcitonin, these cells produce smaller amounts of other peptides, including carcinoembryonic antigen (CEA), which is used as a nonspecific tumor marker in the follow-up of patients with this tumor. MTC is a rare thyroid tumor and occurs three times more often in women than in men. It can occur in two forms, sporadic (80%) and familial form (20%). The familial form can occur alone or in association with other endocrine tumors within MEN 2A and MEN 2B syndromes. The sporadic form most often occurs in the fifth and sixth decades of life. The familial form is inherited autosomally dominantly, most often based on a mutation in the RET protooncogene located on chromosome 10. C-cell hyperplasia is considered to be a premalignant lesion, which precedes medullary carcinoma. Medullary carcinoma metastasizes very early. We presented a patient with a sporadic form of MTC which appeared at a typical age. Initial values of both baseline and stimulated calcitonin were not in the range for suspected MCT, but due to persistent increases in calcitonin, with elevated baseline (63 pg / mL) and higher stimulated calcitonin (96 pg / mL), the patient was referred for surgical treatment. Due to the strong correlation of calcitonin values with tumor size, the initial calcitonin values were expected to be low because the tumor was 3 mm in size. The histopathological diagnosis was C-cell hyperplasia. However, due to the fact that nodular C-cell hyperplasia is histopathologically difficult to distinguish from medullary microcarcinoma, based on the persistent increase in calcitonin levels, the patient was likely to already have metastatic disease at the time of thyroidectomy. Definitive diagnosis was made by liver biopsy. Therapy with tyrosine kinase inhibitors was introduced, and calcitonin levels strarted to decrea, but there is an increase in carcinoembryonic antigen, which is a poor prognostic parameter.

Medullary thyroid carcinoma in children: current state of the art and future perspectives.

Medullary thyroid carcinoma (MTC) is a distinct type of malignant thyroid tumor in cell origin, biological behavior, and natural history. It accounts for 1.6% of all thyroid cancers and presents either sporadically or as a hereditary disease, the latter occurring as a part of multiple endocrine neoplasia (MEN) 2A and MEN2B syndromes or as a familial MTC disease with no other manifestations. The gene responsible for the hereditary form is the rearranged during transfection (RET) gene, a proto-oncogene located to human chromosome 10. Most pediatric MTC cases have been discovered after genetic testing investigations, leading to the concept of prophylactic surgery in presymptomatic patients. Therefore, the genetic status of the child, along with serum calcitonin levels and ultrasonographic findings, determine the appropriate age for prophylactic surgical intervention. Nevertheless, a diagnosis at an early stage of MTC warrants total thyroidectomy and central lymph node dissection with the addition of lateral/contralateral lymph node dissection depending on the tumor size, ultrasonographic evidence of neck disease, or calcitonin levels. Conversely, locally advanced/unresectable or metastatic MTC is primarily treated with multikinase inhibitors, while more specific RET inhibitors are being tested in clinical trials with promising results.

Abstract #1003222: Case Report: Medullary Thyroid Cancer as Part of the MEN2B Syndrome in an 8-year-old Male Patient

Medullary thyroid cancer (MTC) accounts for 5% of all thyroid cancers. MTC originates from the parafollicular of the thyroid, which derive from the neural crest. In children, more than 95% cases of MTC are inherited as part of the multiple endocrine neoplasia syndromes (MEN2A and MEN2B) or familial MTC. MEN2B only represents 5% of MEN2 cases and is associated with a mutation in the M918T of the RET oncogene. MEN2B is characterized by specific phenotypic features, including a marfanoid habit, a prominent jaw, ocular abnormalities, ganglioneuromas and mucosal neuromas.

Unusual case of medullary thyroid cancer

Medullary thyroid carcinomas make up 9,4% of all cancers of the thyroid gland [1]. We can divide them into sporadic and familial form. Sporadic forms are most common. The rest of medullary thyroid carcinomas are familial forms which in most cases are associated with MEN2a and MEN2b syndromes. If neoplasm is associated with MEN2a or MEN2b syndromes, other tumors can occur: pheochromocytoma or adenomas of parathyroids glands. Medullary thyroid carcinoma typically occurs as a solid tumor in the thyroid region of the neck. It can produce also: pain in thyroid region, dysphagia, hoarseness, cervical lymphadenopathy. These symptoms are caused by infiltration of adjacent tissues by neoplasm and by metastases to cervical lymph nodes. It is very rare that there is no tumor in the thyroid region, when a patient complains about signs associated with infiltration of the tumor, but in some cases lymphadenopathy can be the first sign of medullary thyroid carcinoma [2]. Rarer than that there is no tumor in thyroid gland visualized in CT scans when there are signs of cervical lymphadenopathy. In this case report we present the patient with metastases of the medullary thyroid carcinoma to the neck and no other findings in physical examination and additional testing.

Isolated intestinal Ganglioneuromatosis: case report and literature review

BackgroundIntestinal Ganglioneuromatosis (IG) is a rare disorder of the enteric nervous system. In pediatric age it is often associated with genetic syndromes such as Neurofibromatosis 1 (NF1), multiple endocrine neoplasia type 2B (MEN2B) and Cowden syndrome (PTEN mutation), and ganglioneuromas (GNs) may be sometimes the first sign of the disease. Isolated GNs are rare and sporadic. Clinical symptom vary and depend on the size and on the location of the GNs. This disorder affects intestinal motility and it, consequently, causes changes in bowel habits, abdominal pain, occlusive symptoms and rarely lower gastrointestinal bleeding secondary to ulceration of the intestinal mucosa. On the other hand, patients can remain asymptomatic for many years.Case presentationWe describe a 9-year-old boy referred to our emergency department for right lower quadrant abdominal pain. No familial history for gastrointestinal disorders. No history of fever or weight loss. At physical examination, he had diffused abdominal pain. Abdominal ultrasonography showed a hypoechoic formation measuring 41.8 mm by 35 mm in the right lower quadrant of the abdomen. Routine blood tests were normal, but fecal occult blood test was positive. Abdominal TC confirmed the hypodense formation, of about 5 cm in transverse diameter, in the right hypochondrium that apparently invaginated in the caecum-last ileal loop. Colonoscopy showed in the cecum an invaginated polypoid lesion of the terminal ileal loop. Laparoscopic resection of the polypoid lesion was performed. Histological diagnosis of the large neoplasm observed in the terminal ileum was diffuse ganglioneuromatosis. NF1, RET and PTEN gene tests resulted negative for specific mutations. At the 1 year follow-up, the patient presented good general condition and blood tests, fecal occult blood test, esophagogastroduodenoscopy, colonoscopy and MR-enterography were negative.ConclusionsOnly few cases are reported in literature of IG in pediatric age. Although rare, the present case suggests that this disorder must be taken in consideration in every patient with GI symptoms such as abdominal pain, constipation, lower intestinal bleeding, in order to avoid a delayed diagnosis.

Timely diagnosis of multiple endocrine neoplasia 2B by identification of intestinal ganglioneuromatosis: a case series

BackgroundMedullary thyroid carcinoma (MTC) in childhood is rare and has an unfavorable prognosis. To improve outcome, early diagnosis is essential. In patients with multiple endocrine neoplasia type 2B (MEN2B), MTC can occur already before the age of 1 year. Recognition of non-endocrine features of MEN2B may lead to timely diagnosis.PurposeTo describe how early recognition of non-endocrine features can lead to a timely diagnosis of MEN2B as well as the effect of recognition of premonitory symptoms on prognosis.MethodsA retrospective case series from the University Medical Center Utrecht/Wilhelmina Children’s Hospital, a Dutch national expertise center for MEN patients. All eight MEN2B patients in follow-up between 1976 and 2020 were included and medical records reviewed.ResultsIntestinal ganglioneuromatosis (IGN) as the cause of gastrointestinal (GI) symptoms was detected in seven patients. In three of them within months after birth. This led to early diagnosis of MEN2B, which allowed subsequent curative thyroid surgery. On the contrary, a MEN2B diagnosis later in childhood—in three patients (also) triggered by oral neuromas/neurofibromas—led to recurrent, persistent, and/or progressive MTC in five patients.ConclusionsNeonatal GI manifestations offer the most important window of opportunity for early detection of MEN2B. By accurate evaluation of rectal biopsies in patients with early onset severe constipation, IGN can be timely detected, while ruling out Hirschsprung’s disease. MEN2B gene analysis should follow detection of IGN and—when confirmed—should prompt possibly still curative thyroid surgery.

A Rare Case of Diffuse Intestinal Ganglioneuromatosis in a Child Presenting with Intussusception

Ganglioneuromas are benign neurogenic neoplasms commonly seen in children which are originating from neural crest cells of sympathetic ganglia or adrenal medulla. Rarely, they may arise from the visceral organs like intestine. Diffuse intestinal ganglioneuromatosis is a rare disease, caused due to abnormal proliferation of ganglion cells, nerve fibres and schwann cells in the wall of intestine. Author hereby present a case of diffuse intestinal ganglioneuromatosis in an 18-month-old male child who presented with symptoms of small bowel obstruction. Resected segment of ileocecal junction revealed ulcero-nodular areas which on microscopy showed diffuse hyperplasia of nerve bundles and ganglion cells with immunohistochemistry confirmation. Intestinal ganglioneuromatosis is a rare condition having syndromic association with MEN-2B, Neurofibromatosis-1 and Cowden syndrome. As this disease has a low clinical suspicion, very nonspecific symptoms and radiological findings, histopathological examination becomes mainstay in diagnosis. Further workup is essential to rule out presence of associated syndromes.Surgical excision is the ultimate treatment with screening for genetic abnormalities.

S1648 A Colon Polyp from Outside the BOX—Schwann Cell Hamartomatous Polyp

INTRODUCTION: A positive cologuard leads to a colonoscopy that can show typical polyps of the gastrointestinal (GI) mucosa. Still rare, GI tract nerve sheath tumors have become more common.1 Nerve sheath tumors are rare in the GI tract but common in skin and soft tissue.2 Some GI nerve sheath tumors have malignant potential or can be affiliated with inherited polyposis syndromes and require histological and immunostaining evaluation to differentiate the polyps. A variant of nerve sheath tumors is Schwann cell hamartoma, described in a large case series by Gibson and Hornick.3 CASE DESCRIPTION/METHODS: 70 year-old female with hypertensive and diabetic history had a colonoscopy for a positive Cologuard. Colonoscopy showed two 3-4 mm polyps in the ascending colon, removed by cold biopsy forceps, entire colon diverticulosis and internal hemorrhoids. Normal ileal mucosa and bleeding. Biopsied polyps showed hyperplastic polyp and Schwann cell hamartoma, staining S-100 positive and cytokeratin AE1/AE3 negative (Image 1,2). DISCUSSION: Polyps with neural histology have a differential diagnosis of schwannomas, neurofibromas, leiomyomas, perineuriomas, ganglioneuromas, and granular cell tumor.3,4 Neurofibromas, mucosal neuromas and ganglioneuroma lesions are often associated with Neurofibromatosis type 1, Multiple Endocrine Neoplasia Type 2b and Cowden syndrome respectively.2 Schwann cell hamartoma are GI Schwannomas that are not affiliated with inherited syndromes. 3,4 They are often both small polyps ranging from 1-6mm and left-sided colonic lesions specifically seen in the rectosigmoid colon. Grossly they are polypoid lesions and histologically show neural proliferation but absence of ganglion cells.2,3,4 All neuronal etiology polyps have diffuse proliferation of spindle cells in the lamina propria. All Schwann cell hamartomas stain strongly positive for S-100. They have no staining of neurofilament protein while the opposite is true for neurofibromas.2 It is important to distinguish schwannomas from Schwann cell hamartomas. Both stain positive for S-100, but schwannomas are typically found in the stomach and noted to have peripheral cuff-like lymphoid aggregates with germinal centers, composed exclusively of Schwann cells.2 It is important to differentiate neuronal histologic polyps to discern underlying malignancy or inherited syndrome. Importantly, Schwann cell hamartomas have all been described being discovered incidentally with benign clinical courses, consistent with what is seen in our patient.Figure 1.: Hematoxylin and eosin shows scattered proliferation of bland spindle cells in the lamina propria.Figure 2.: Immunohistochemical staining for S-100 displays a positivity of both nucleus and cytoplasm.

S1737 A Rare Case of an Appendiceal Mucosal Schwann-Cell Hamartoma

INTRODUCTION: Mucosal Schwann-cell hamartomas (MSCH) are a relatively new and rare pathological entity. These neuronal sheath polyps are distinct from neuromas and neurofibromas since are composed of Schwann cells that show diffuse positivity to S-100 stain. Case reports have described these polyps as small (< 1cm), usually located on the left side of the colon and predominantly seen in middle-age female patients. We present a rare case of a MSCH located in the appendix. CASE DESCRIPTION/METHODS: 73 y/o asymptomatic male with history of type II diabetes mellitus, hypertension, and hypothyroidism. The patient had a previous colonoscopy with two tubular adenomas less than 1cm in size on the transverse colon; but no personal or family history of colon cancer. He was referred for a surveillance colonoscopy. Colonoscopy revealed an erythematous polyp at the appendiceal orifice and 4 additional diminutive sessile polyps at the transverse colon, hepatic flexure, sigmoid and rectum, respectively. All were removed with cold biopsy forceps. Pathology revealed an appendiceal MSCH, 3 tubular adenomas in hepatic flexure, transverse colon and sigmoid, respectively and 1 hyperplastic polyp at rectum. Immunohistochemistry relevant for diffuse strong positivity for S-100 protein in the appendiceal lesion. DISCUSSION: Gibson and Hornick (2009) first described these colorectal polyps of mesenchymal cell origin as mucosal Schwann cell hamartomas to distinguish them from other benign or malignant lesions. These neuronal polyps are sporadic and have not been associated to inherited syndromes like type 1 neurofibromatosis or multiple endocrine neoplasia type 2B. Differential diagnosis of MSCH include neurofibromas, ganglioneuromas, neuromas, perineuromas, inflammatory fibroid polyps and gastrointestinal stromal tumors. The latter is the most common spindle cell tumor in the gastrointestinal tract, but it can be easily distinguished from the MSCH by their immunoreactivity to c-kit. After excluding other more common lesions, histological evidence of spindle cell proliferation within the lamina propria and immunohistochemistry stain diffusely positive for S-100 can establish the diagnosis of MSCH. Given the rarity of this benign and incidental polyp, there are no established guidelines for surveillance. Awareness of this entity is relevant to pathologists and gastroenterologists and raises the importance of immunostaining when evaluating spindle cell tumors to avoid unnecessary treatment and establish an accurate diagnosis.Figure 1.: Appendiceal polyp measuring <0.5 cm seen in surveillance colonoscopy.Figure 2.: Sections of the biopsy show focal expansion of the lamina propria by a spindle cell proliferation.Figure 3.: Immunohistochemical stains show the spindle cells to be strong and diffusely positive for S-100.

Molecular Diagnosis and Treatment of Multiple Endocrine Neoplasia Type 2B in Ethnic Han Chinese.

Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and non-endocrine features. However, the diagnosis and treatment are usually delayed. This study reports 5 Chinese pedigrees with 5 individuals harboring germline RETM918T, and systematically reviewed previous Chinese literature reported. All 5 patients initially presented MTC, but none had biochemically cured postoperatively. 2 also presented bilateral PHEO after adrenal-sparing surgery, 1 needed steroid replacement. Further, a total of 32 MEN 2B patients from literature were clustered with 28 available for analysis. 26 (92.8%) were diagnosed by endocrine-related symptoms; the remaining 2 (7.2%) due to RET testing and oral symptoms, respectively. 25 patients underwent thyroidectomy with/without neck lymph node dissection at the mean age of (23.3 ± 10.4) years. Histopathological examination revealed MTC (100%). Of them, 17 had definite TNM stage, with 1 in stage III and others in IV. Other information of MEN 2B-related symptoms included penetrance of PHEO (60.7%), constipation (32.1%), Hirschsprung disease (25%), alacrima (17.8%), mucosal ganglioneuroma (96.4%) and marfanoid habitus (71.4%). 19 patients were verified harboring RET-M918T (c.2753T>C), of whom 15 (78.9%) were de novo mutation. The other 9 were clinically diagnosed as MEN 2B. The initial diagnosis of MEN 2B is relatively later, and diagnosed by non-endocrine components is extremely lower. Recognition of MEN 2B and its non-endocrine-related components is still the utmost requirement for a Chinese physician. Combined RET screening and serum calcitonin detection can facilitate early diagnosis.

Metastatic Medullary Thyroid Carcinoma as a Presenting Feature of Multiple Endocrine Neoplasia 2B: A Case Report and Literature Review

Background: Multiple Endocrine Neoplasia type 2B (MEN2B) is an autosomal dominant disorder characterized by Medullary Thyroid Carcinoma (MTC) and pheochromocytoma. MTC occurs in almost all MEN2B patients. The tumor develops at an earlier age and is aggressive. Surgery is often not curative for this condition. Death from MTC occurred in 50% of patients with MEN2B. Thus, early diagnosis and prevention are crucial in this regard. Thyroidectomy, as early as the neonatal period, may be indicated in patients with MEN2B identified by genetic screening. Case Presentation: We reported a 24-year-old male presented to the emergency department with dyspnea for the past 3 months. There was a nodule 3*3 cm in the Right Lower Lobe (RLL) of the thyroid gland. Non-contrast Computer Tomography (CT) scan of the lung revealed multiple nodular lesions compatible with metastasis. The Fine Needle Aspiration (FNA)cytology of the thyroid nodule indicated that the features of medullary thyroid carcinoma were positive stains in Immunohistochemistry (IHC) for calcitonin. A diagnosis of pulmonarymetastatic medullary thyroid carcinoma, as a presenting feature of MEN2B, was made. The patient was treated with Vandetanib. Conclusion: In the reported MEN2B patient, MTC occurred in the early stages of life and was multifocal. Thus, it is crucial to diagnose medullary thyroid cancer at the early stages of the disease.