A Huge Pelvic-Abdominal Malignant GIST Tumour in a Patient with Neurofibromatosis Type 1: Case Report and Literature Review

Gastrointestinal stromal tumours are rare tumours of the gastrointestinal tract (GIT) accounting for 0.1%–3% of all gastrointestinal tumours. The most common location is the stomach (55%) followed by the small bowel (31.8%), colon (6%), other various locations (5.5%), and the oesophagus (0.7%). They may also occur in extraintestinal locations. The signs and symptoms of GIST depend on the tumour’s location and size. Gastrointestinal bleeding is one of the most common symptoms. Other signs and symptoms include abdominal discomfort, pain or distention; intestinal obstruction, and weight loss. The association between the development of GISTs and neurofibromatosis 1 (NF1) has been established. NF1-associated GISTs tend to have a distinct phenotype, and the absence of KIT/PDGRFα mutations in turn has implications on further management when they do not respond well to imatinib treatment. Here, we present one of the largest GISTs reported in the literature with a total volume of 25.3×20×14 cm+27.9×23×8 cm and an overall weight of 7.3 kg, which developed in a 43-year-old female patient with NF1 and was resected on an emergency basis due to the rapid deterioration and development of abdominal compartment syndrome. Pathology assessment showed a malignant GIST composed of spindle cells with elongated nuclei with necrosis, marked pleomorphism and numerous giant cell. The mitotic count was >15/50 HPF, Ki 67 was 80%, and the lymphovascular invasion was clear. Immunohistochemistry investigations showed that Vimentin, CD117, and DOG1 were positive, while BCL-2 and CD99 were focal positives. Pan-CK, S-100, CD34, Desmin, SMA, and HMB-45 were negatives.

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Inflammatory myofibroblastic tumour causing intestinal obstruction in a patient with neurofibromatosis type 1

Annals of The Royal College of Surgeons of England ◽

10.1308/rcsann.2020.7003 ◽

2021 ◽

Vol 103 (2) ◽

pp. e53-e55

Author(s):

XE Chuang ◽

DYS Chan ◽

ML Oon ◽

S Wang ◽

CLK Chia

Keyword(s):

Intestinal Obstruction ◽

Neurofibromatosis Type 1 ◽

Bowel Resection ◽

Neurofibromatosis Type ◽

Resection Margins ◽

Soft Tissue Tumours ◽

En Bloc ◽

Biological Behaviour ◽

Rare Tumours

Inflammatory myofibroblastic tumours (IMTs) are rare tumours with unpredictable biological behaviour ranging from benign to locally invasive and rarely, distant metastasis. While neurofibromatosis type 1 (NF1) may manifest with gastrointestinal soft tissue tumours, this is the first report in the literature that describes an IMT occurring in a NF1 patient who presented with intestinal obstruction. Our patient presented with intestinal obstruction secondary to an obstructing terminal ileum mesenteric tumour. En bloc bowel resection was performed, with histology revealing an IMT and an adjacent neurofibroma. The resection margins were clear and the patient was free of recurrence at six months.

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Adrenal incidentaloma in neurofibromatosis type 1

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0806295t ◽

2008 ◽

Vol 136 (5-6) ◽

pp. 295-298

Author(s):

Milina Tancic-Gajic ◽

Svetlana Vujovic ◽

Svetislav Tatic ◽

Milos Stojanovic ◽

Miomira Ivovic ◽

...

Keyword(s):

Neurofibromatosis Type 1 ◽

Plexiform Neurofibroma ◽

Fatal Outcome ◽

Clinical Manifestations ◽

Adrenal Incidentaloma ◽

Neurofibromatosis Type ◽

Clinical Criteria ◽

Abdominal Magnetic Resonance Imaging ◽

Rare Tumours

INTRODUCTION Neurofibromatosis type 1 is one of the most common genetically transmitted diseases with a high index of spontaneous mutations and extremely varied and unpredictable clinical manifestations. It is diagnosed by the existence of certain clinical criteria. The presence of numerous localised cutaneous neurofibromas or a plexiform neurofibroma is virtually pathognomonic of neurofibromatosis type 1. The incidence of pheochromocytoma in neurofibromatosis type 1 is 0.1-5.7%. CASE OUTLINE A 56-year old female patient was admitted for further evaluation of incidental adrenal tumour previously diagnosed on computerized tomography (CT). She had previously unrecognized neurofibromatosis type 1 and a clinical picture which could remind of pheochromocytoma. None of the catecholamine samples in 24 hr urine indicated functionally active pheochromocytoma. Chromogranin A was moderately increased. Decision for operation was made after performing the image techniques. Adrenal incidentaloma had features of pheochromocytoma on abdominal magnetic resonance imaging (MRI), with positive 131I-MIBG (iodine 131-labelled metaiodobenzylguanidine scintigraphy). After being treated with phenoxybenzamine and propranolol, she was operated on. The pathohistological finding showed the case of left adrenal pheochromocytoma. CONCLUSION Detailed diagnostic procedure for pheochromocytoma should be performed with patients having neurofibromatosis type 1 and adrenal incidentaloma. Pheochromocytomas are rare tumours with fatal outcome if not duly recognized and cured.

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A rare presentation of superficial, inter-muscular, cystic, extra-spinal schwannoma over upper back.

10.21203/rs.3.rs-38097/v2 ◽

2020 ◽

Author(s):

Srinjoy Saha

Keyword(s):

Signs And Symptoms ◽

Surgical Excision ◽

The Body ◽

Thoracic Vertebrae ◽

Rare Presentation ◽

Complete Surgical Excision ◽

Rare Tumours ◽

S 100 ◽

Diagnostic Signs ◽

Upper Thoracic

Abstract Schwannomas are rare tumours arising from peripheral nerve sheath and are usually related to the spinal cord and spinal nerves. Contrast magnetic resonance imaging (MRI) usually helps in establishing a pre-operative diagnosis. Rarely, their manifestation may be surprisingly new. Here, a 44-year-old lady came to our clinic with a painless asymptomatic progressively enlarging swelling over her upper back. It was fluctuant, with absent neural signs and symptoms. MRI showed a benign, purely-cystic, superficial-intermuscular, extra-spinal swelling near the upper thoracic vertebrae. However, classical diagnostic signs of schwannoma were absent. Complete surgical excision was performed with smooth dissection through a well-defined plane between the lesion and surrounding muscles. A 6.5x5.0x2.5 cm oval lesion with a glistening whitish-grey capsule was excised, and the deep wound was reconstructed in multiple layers. Interestingly, it was not attached to any identifiable nerves. Histopathology showed typical hallmarks like Antoni A regions and Verocay bodies. Positive S-100 staining during immunohistochemistry established its diagnosis as schwannoma. The postoperative one-and-half-year follow-up period was uneventful. Cystic schwannomas can surprise and confuse clinicians by arising anywhere in the body and with atypical manifestations. Surgeons need to consider it in the differential diagnoses of any undiagnosed slowly-growing swelling, including purely-cystic ones and perform careful surgical dissection to avoid any inadvertent nerve damage.

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A Case of Giant Posterior Mediastinal Mass: Gastrointestinal Stromal Tumor Developed in Neurofibromatosis Type 1 Patient.

10.21203/rs.3.rs-748331/v1 ◽

2021 ◽

Author(s):

Volkan ASLAN ◽

Fatih Gürler ◽

ozan yazıcı ◽

özlem erdem ◽

ali çelik ◽

...

Keyword(s):

Histopathological Examination ◽

Genetic Disorders ◽

Neurofibromatosis Type ◽

Skin Lesions ◽

Posterior Mediastinum ◽

Pathological Examination ◽

Imatinib Treatment ◽

First Case ◽

Posterior Mediastinal

Abstract Introduction: Gastrointestinal Stromal Tumors mostly located in the stomach and esophageal GIST is extremely rare. Various genetic disorders increase the risk of developing GIST, among these, NF-1 is the most common. A case of posterior mediastial GIST developing in the neurofibromatosis patient has not been reported yet.Case: A 48-year-old male patient is being evaluated with complaints of dyspnea and progressive dysphagia. Computed tomography detected a cystic, lobulated contour mass that was located at the posterior mediastinum and measuring 11 x 14x12 cm. The giant semisolid mass has been dissected from adjacent the vertebra, the esophagus, pericardium and inferior pulmonary vein and Histopathological examination revealed GİST. Pathological examination of skin lesions confirmed NF-1. Finally, NF-1-associated posterior mediastinal GIST was diagnosed and adjuvant imatinib treatment was initiated. Conclusion: To the best our knowledge, this patient was the first case, who diagnosed with posterior mediastinal GIST developing on the basis of NF-1.

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Frequent EGFR Positivity and Overexpression in High-Grade Areas of Human MPNSTs

Sarcoma ◽

10.1155/2008/849156 ◽

2008 ◽

Vol 2008 ◽

pp. 1-7 ◽

Cited By ~ 22

Author(s):

Séverine Tabone-Eglinger ◽

Radislav Bahleda ◽

Jean-François Côté ◽

Philippe Terrier ◽

Dominique Vidaud ◽

...

Keyword(s):

Growth Factor Receptor ◽

Survivin Expression ◽

Neurofibromatosis Type ◽

High Grade ◽

Rt Pcr ◽

Ki 67 ◽

Egfr Expression ◽

Epidermal Growth

Malignant peripheral nerve sheath tumours (MPNSTs) are highly malignant and resistant. Transformation might implicate up regulation of epidermal growth factor receptor (EGFR). Fifty-two MPNST samples were studied for EGFR, Ki-67, p53, and survivin expression by immunohistochemistry and forEGFRamplification by in situ hybridization. Results were correlated with clinical data.EGFRRNA was also quantified by RT-PCR in 20 other MPNSTs and 14 dermal neurofibromas. Half of the patients had a neurofibromatosis type 1 (NF1). EGFR expression, detected in 86% of MPNSTs, was more frequent in NF1 specimens and closely associated with high-grade and p53-positive areas. MPNSTs expressed moreEGFRtranscripts than neurofibromas. No amplification ofEGFRlocus was observed. NF1 status was the only prognostic factor in multivariate analysis, with median survivals of 18 and 43 months for patients with or without NF1. Finally, EGFR might become a new target for MPNSTs treatment, especially in NF1-associated MPNSTs.

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A rare presentation of superficial, inter-muscular, cystic, extra-spinal schwannoma over upper back

Neurologico Spinale Medico Chirurgico ◽

10.36444/nsmc.v3i3.120 ◽

2020 ◽

Vol 3 (3) ◽

pp. 103-106

Author(s):

Srinjoy Saha

Keyword(s):

Signs And Symptoms ◽

Surgical Excision ◽

The Body ◽

Thoracic Vertebrae ◽

Rare Presentation ◽

Complete Surgical Excision ◽

Rare Tumours ◽

S 100 ◽

Diagnostic Signs ◽

Upper Thoracic

Schwannomas are rare tumours arising from peripheral nerve sheath and are usually related to the spinal cord and spinal nerves. Contrast magnetic resonance imaging (MRI) usually helps in establishing a pre-operative diagnosis. Rarely, their manifestation may be surprisingly new. Here, a 44-year-old lady came to our clinic with a painless asymptomatic progressively enlarging swelling over her upper back. It was fluctuant, with absent neural signs and symptoms. MRI showed a benign, purely-cystic, superficial-intermuscular, extra-spinal swelling near the upper thoracic vertebrae. However, classical diagnostic signs of schwannoma were absent. Complete surgical excision was performed with smooth dissection through a well-defined plane between the lesion and surrounding muscles. A 6.5x5.0x2.5 cm oval lesion with a glistening whitish-grey capsule was excised, and the deep wound was reconstructed in multiple layers. Interestingly, it was not attached to any identifiable nerves. Histopathology showed typical hallmarks like Antoni A regions and Verocay bodies. Positive S-100 staining during immunohistochemistry established its diagnosis as schwannoma. The postoperative one-and-half-year follow-up period was uneventful. Cystic schwannomas can surprise and confuse clinicians by arising anywhere in the body and with atypical manifestations. Surgeons need to consider it in the differential diagnoses of any undiagnosed slowly-growing swelling, including purely-cystic ones and perform careful surgical dissection to avoid any inadvertent nerve damage.

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Cystic Pancreatic Neuroendocrine Tumor in a Patient with Neurofibromatosis Type 1

Case Reports in Gastroenterology ◽

10.1159/000510210 ◽

2021 ◽

pp. 108-114

Author(s):

Hiroharu Shinozaki ◽

Yuuichi Sasakura ◽

Satoshi Shinozaki ◽

Toshiaki Terauchi ◽

Junichi Matsui ◽

...

Keyword(s):

Neurofibromatosis Type 1 ◽

Preoperative Diagnosis ◽

Pelvic Mass ◽

External Iliac Artery ◽

Immunohistochemical Analysis ◽

Neurofibromatosis Type ◽

Cystic Tumor ◽

High Power Field ◽

Ki 67

Neurofibromatosis type 1 (NF-1) is strongly associated with neurofibromas and malignancies. Solid pancreatic neuroendocrine tumors (PanNETs) have been recently reported in patients with NF-1. PanNETs are always solid and rarely present with a cystic appearance due to central necrosis and hemorrhage caused by rapid growth. A 33-year-old female diagnosed with NF-1 at age 16 was referred for evaluation of a pelvic mass found on abdominal ultrasound. Magnetic resonance imaging showed a 6 cm solid pelvic mass adjacent to the left external iliac artery, and contrast-enhanced computed tomography scan showed a 3-cm solid para-aortic mass and a 3-cm cystic mass in the pancreatic tail. Endoscopic ultrasonography showed a cystic tumor with necrotic tissue and septa. Preoperative diagnosis was pancreatic cystic malignancy with para-aortic lymph node metastasis accompanied with a pelvic neurofibroma. These lesions were resected simultaneously. The specimen resected from the pancreas showed a necrotizing cystic tumor invading abutting lymph nodes. Immunohistochemical analysis showed positive chromogranin A and synaptophysin. The Ki-67 index was <1%, and the mitotic count was 1/10 in high power field. Therefore, a non-functional PanNET (grade G1) was diagnosed. The pelvic and para-aortic tumors were both neurofibromas. A cystic appearance is atypical for PanNET and makes preoperative diagnosis difficult. To the best of our knowledge, this is the first report of a cystic PanNET in a patient with NF-1.

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Unusual Case of Multiple Synchronous Gastrointestinal Stromal Tumors of the Jejunum Presenting as an Arteriovenous Malformation

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.121 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S56-S56

Author(s):

A Murzabdillaeva ◽

H Taha ◽

R J Hausner

Keyword(s):

Arteriovenous Malformation ◽

Epigastric Pain ◽

Surgical Excision ◽

Neurofibromatosis Type ◽

Proliferation Index ◽

Double Balloon Enteroscopy ◽

Ki 67 ◽

Genetic Features ◽

Carney’S Triad

Abstract Introduction/Objective Gastrointestinal stromal tumor (GIST) arises from the interstitial cell of Cajal. 30% of GISTs arise in the jejunum. GISTS are generally solitary although multiple GISTs may be synchronous or metachronous. There are a few reports of a GIST of the jejunum mimicking a vascular malformation/arteriovenous malformation (AVM) prior to surgical excision. Methods Herein, we report a case of four synchronous GISTs of jejunum. One GIST, highly vascularized, presented with lower gastrointestinal bleeding. The patient was a 40-year-old female presenting with epigastric pain and melena. Results She was found to have an ulcerated lesion in the distal jejunum by capsule enteroscopy and double balloon enteroscopy, interpreted as an arteriovenous malformation and tattooed. Several other non-ulcerated “polyps” were described. Gross examination of the ensuing segmental resection of jejunum demonstrated four bosselated tumors ranging from 3.1 cm to 6.5 cm. Microscopically, three tumors did not extend to the surface of the jejunum and were predominantly composed of spindle cells. One tumor (identified by tattoo) extended to the surface with ulceration. This tumor was dominated by wide vascular channels with a spindle cell component between the channels. The four tumors were each positive for CD117, DOG1, and Succinate dehydrogenase B (SDH), identifying the four tumors as non-SDH-deficient GISTs. Ki-67 proliferation index was less than 5% in all four masses. Conclusion Multiple GISTs are rare, classified as either sporadic or familial. Familial GEISTs are described in neurofibromatosis type 1, Carney’s triad and Carney-Stratakis syndrome. Pediatric GISTs, with clinical and genetic features often differing from typical adult tumors may also be multiple. Our patient’s four GISTs are considered multiple synchronous sporadic neoplasms. This case serves as an important reminder for pathologists consider GIST in the evaluation of a highly vascular gastrointestinal proliferation and keep in mind the possibility of multiplicity.

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The clinico-pathologic profile of primary and recurrent orbital/periorbital plexiform neurofibromas (OPPN)

PLoS ONE ◽

10.1371/journal.pone.0258802 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258802

Author(s):

Mohammad Alabduljabbar ◽

Diego Strianese ◽

Osama Al-Sheikh ◽

Hind M. Alkatan ◽

Hailah Al-Hussain ◽

...

Keyword(s):

Alcian Blue ◽

Smooth Muscle Actin ◽

Neurofibromatosis Type ◽

Proliferation Index ◽

Diffuse Type ◽

Ki 67 ◽

Primary Tumors ◽

Plexiform Neurofibromas ◽

Recurrent Tumors ◽

S 100

To evaluate and compare the clinical and histopathological profile of primary and recurrent orbital-periorbital plexiform neurofibromas (OPPN) in patients with neurofibromatosis type 1. We retrospectively evaluated 43 primary or recurrent neurofibroma (NF) specimens from 26 patients (2002 to 2018) at the King Khaled Eye Specialist Hospital, Saudi Arabia. Demographics, clinical presentation, and surgical intervention data were collected. Histopathological specimens were studied with hematoxylin-eosin, Alcian blue, and immunohistochemical markers; S-100, CD44, CD117, smooth muscle actin (SMA), neurofilament, and Ki-67. Of the 43 NFs specimens, 20 were primary and 23 recurrent tumors. For primary NF, the ratio of plexiform to the diffuse type was 13:7, however in recurrent tumors was 3:8 after the first recurrence, and 1:5 after multiple recurrences. Of the 17 patients with primary tumors that had paired recurrent tumors, 12/17 (70.6%) primary NFs were plexiform and 5/17 (29.4%) were diffuse. However, when tumors recurred, 13/17 tumors (76.5%) were diffuse and only 4/17 tumors (23.5%) had a plexiform pattern. The odds of a tumor having a diffuse pattern in recurrent NF was significantly higher than the plexiform pattern [OR = 7.8 (95% confidence interval 1.69:36.1) P = 0.008]. Primary plexiform NFs underwent an excision at a significantly younger age than the diffuse type. Recurrent NFs had significantly higher CD44, CD117, and neurofilament labeling (P = 0.02, P = 0.01 and P<0.001 respectively) but had significantly decreased Alcian blue, and S-100 labeling (P = 0.03, and P = 0.02 respectively) compared to primary tumors. SMA and Ki-67 proliferation index were not different between primary and recurrent NFs (P = 0.86, and P = 0.3 respectively). There appears to be a high risk for primary plexiform NFs to develop a diffuse histologic pattern when they recur. Immunohistochemical staining suggests a role of mast cells (CD117) and expression of infiltration makers (CD44) in the transformation of plexiform tumors to the diffuse phenotype.

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An unusual case of schwannomatosis with bilateral maxillary sinus schwannomas and a novel SMARCB1 gene mutation

Journal of Neurosurgery Spine ◽

10.3171/2015.4.spine15192 ◽

2016 ◽

Vol 24 (1) ◽

pp. 160-166 ◽

Cited By ~ 2

Author(s):

Jamie Toms ◽

Jason Harrison ◽

Hope Richard ◽

Adrienne Childers ◽

Evan R. Reiter ◽

...

Keyword(s):

Maxillary Sinus ◽

Unusual Case ◽

Novel Mutation ◽

Signs And Symptoms ◽

Neurofibromatosis Type ◽

The Body ◽

Benign Tumors ◽

Exon 1 ◽

Multiple Schwannomas

Schwannomas are benign tumors that arise from Schwann cells in the peripheral nervous system. Patients with multiple schwannomas without signs and symptoms of neurofibromatosis Type 1 or 2 have the rare disease schwannomatosis. Tumors in these patients occur along peripheral nerves throughout the body. Mutations of the SMARCB1 gene have been described as one of the predisposing genetic factors in the development of this disease. This report describes a patient who was observed for 6 years after having undergone removal of 7 schwannomas, including bilateral maxillary sinus schwannomas, a tumor that has not been previously reported. Genetic analysis revealed a novel mutation of c.93G>A in exon 1 of the SMARCB1 gene.

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