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Mucosal Schwann cell hamartoma of gall bladder: a novel observation

2018; Elsevier BV; Volume: 50; Issue: 4 Linguagem: Inglês

10.1016/j.pathol.2017.11.095

1465-3931

Gaurav Khanna, Shouriyo Ghosh, Adarsh Barwad, Rajni Yadav, Prasenjit Das,

Testicular diseases and treatments

Benign nerve sheath tumours are commonly seen as superficial cutaneous or soft tissue compartment lesions. They are relatively uncommon in the gastrointestinal (GI) tract and present as polypoid masses, histologically typified as schwannomas, ganglioneuromas and perineuriomas.1Sarlomo-Rikala M. Miettinen M. Gastric schwannoma–a clinicopathological analysis of six cases.Histopathology. 1995; 27: 355-360Google Scholar, 2Namikawa T. Kawanishi Y. Fujieda Y. et al.Neurofibroma of the gallbladder not associated with neurofibromatosis.Surg Technol Int. 2016; 30: 89-92Google Scholar Syndromic association has been observed when these lesions are multiple.1Sarlomo-Rikala M. Miettinen M. Gastric schwannoma–a clinicopathological analysis of six cases.Histopathology. 1995; 27: 355-360Google Scholar, 2Namikawa T. Kawanishi Y. Fujieda Y. et al.Neurofibroma of the gallbladder not associated with neurofibromatosis.Surg Technol Int. 2016; 30: 89-92Google Scholar Mucosal Schwann cell hamartoma (SCH) is a recently described benign neural lesion of intestinal mucosa characterised by pure Schwann cell proliferation and with no known syndromic association.3Gibson J.A. Hornick J.L. Mucosal Schwann cell “hamartoma”: clinicopathologic study of 26 neural colorectal polyps distinct from neurofibromas and mucosal neuromas.Am J Surg Pathol. 2009; 33: 781-787Google Scholar, 4Bae M.N. Lee J.E. Bae S.M. et al.Mucosal Schwann-cell hamartoma diagnosed by using an endoscopic snare polypectomy.Ann Coloproctol. 2013; 29: 130-134Google Scholar Immunohistochemical (IHC) stains may be necessary to differentiate SCH of gall bladder from other mimics.2Namikawa T. Kawanishi Y. Fujieda Y. et al.Neurofibroma of the gallbladder not associated with neurofibromatosis.Surg Technol Int. 2016; 30: 89-92Google Scholar Among the reported cases of intestinal SCH, no recurrence has yet been reported. However, due to their rarity, their exact significance is also not known.3Gibson J.A. Hornick J.L. Mucosal Schwann cell “hamartoma”: clinicopathologic study of 26 neural colorectal polyps distinct from neurofibromas and mucosal neuromas.Am J Surg Pathol. 2009; 33: 781-787Google Scholar, 4Bae M.N. Lee J.E. Bae S.M. et al.Mucosal Schwann-cell hamartoma diagnosed by using an endoscopic snare polypectomy.Ann Coloproctol. 2013; 29: 130-134Google Scholar In this retrospective study, our primary aim was to see whether SCH-like lesions exist in gall bladder mucosa and examine the associated mucosal pathology. After incidentally identifying a lesion similar to SCH in a case of chronic cholecystitis, we reviewed all cholecystectomy cases (n = 500) performed for documented cholelithiasis between November 2015 and June 2016 from our departmental archives. Demographic, clinical, operative details and history of associated comorbidity of every patient was obtained from the case records. Topographic details including site and size of lesions and wall thickness of gall bladder were noted from digital image archives. Surgically resected specimens with mucosal dysplasia or malignancies were not included in this retrospective study. As per our routine grossing protocol, at least three sections each from fundus and body of gall bladder were available on two slides from each specimen for review. Written informed consent was taken from all these patients prior to cholecystectomy. The archived slides were screened by GK, SG, RY and PD. The presence of spindle cell proliferation having wavy tapered nuclei in a background of myxoid stromal material was taken as suggestive of SCH. The overlying mucosal lining was carefully observed for any associated morphological change. Configuration of the lesion within the mucosa, mitotic activity, nuclear atypia, type of inflammatory cell infiltrate, necrosis, presence of tactoid (glomeruloid aggregates of spindle cells) bodies, presence of cholesterolosis, hypertrophied nerve bundle in-between layers of muscularis propria, muscle hypertrophy, mucosal eosinophilia, mucosal neutrophilic activity, etc., were identified and noted. Out of the 500 cases of cholecystectomy screened, 20 suspected cases of SCH were subjected to IHC analysis. The following IHC stains were performed in these cases: S100 (Thermo Scientific, USA; 1:200), CD34, NSE, smooth muscle actin and CD34 (all Spring Bio, USA; 1:200), CD56 (Spring Bio; 1:50) and CD117 (BioSB, USA; 1:250), as per our institutional overnight IHC protocol. Positivity in more than 10% of cells was taken as significant. Any background staining was disregarded and the sections were re-stained for evaluation. Of the 500 cholecystectomy specimens reviewed, mucosal SCH-like lesions were present in 20 (4%). While the preoperative diagnosis in all was chronic cholecystitis, in one case polypoid mucosal lesions (measuring 0.5–1.0 cm in diameter) were documented in the radiology note. The age of these patients was between 10 and 56 years, with a median age of 25 years; 15 of these 20 patients (75%) were females and five were male. Our cohort of cases where SCH was not identified also showed similar female predominance (75.4%). Examination of gross photographs did not reveal any definite mucosal lesions apart from variable wall thickness of the gall bladders. In one case, intraluminal mucosal polyps of 2–4 mm in diameter were noted. Gall stones were identified pre-operatively in all and were confirmed during grossing. On histological examination, the villi in gall bladder mucosa showed bulbous expansion or drum-stick appearance because of the presence of this lesion in lamina propria (Fig. 1A–C, arrows). The SCH-like lesions were characterised by short bundles of spindle cells with wavy tapered nuclei, indistinct cytoplasmic margins, situated in a loose myxoid matrix in the lamina propria, just beneath the surface epithelium (Fig. 1B–D). The lesions were un-encapsulated and thin dilated capillaries were commonly noted interspersed within the lesion (Fig. 1B,C). The spindle cell fascicles were oriented both in horizontal as well as vertical planes within the lamina propria, with respect to the longitudinal axis of mucosal villi. Mitosis, necrosis and ganglion cells were not seen in any of the cases. The stroma in the background of the lesion was loose, myxoid and devoid of collagen fibres. The microscopic dimensions of the lesions ranged from 1–3 mm and were mostly diffusely distributed in the sections examined. In all cases the inter-muscular plexus and adventitia were examined to identify presence of any neuromatoid hypertrophy (Fig. 1E, CD56 stained section). In five of these cases, whorled tactile corpuscle structures or tactoid bodies were noted inside the lesions (Fig. 1A,C).5Vandana U.G. Ravikala V.R. Dinesh U.S. Isolated polypoid ganglioneuroma of gall bladder – a case report.Al Ameen J Med Sci. 2011; 4: 295-298Google Scholar Variable lymphocytic cell infiltrate was seen in 13 of these 20 cases (65%); while in four, significant plasma cell infiltrate was identified. In only two out of 20 cases (10%) neutrophilic infiltrate was noted in mucosa adjacent to the lesions. Eosinophils were not significantly increased. In eight of these cases (40%) cholesterolosis was also identified in mucosa in close proximity to the SCH-like lesions. Pyloric metaplasia was frequently noted. In most of the cases (11/20, 55%) the surface mucosal epithelium overlying the SCH-like lesions was denuded (Fig. 1B,D). In two cases the mucosa was completely sloughed off. Hypertrophy of muscularis propria (Fig. 1A,E) was noted in nine of 20 cases (45%), and in 11 of 20 cases (55%) hypertrophied nerve bundles were observed in the inter-muscular nerve plexus. IHC stains showed diffuse immunopositivity of lesion cells for S100 (Fig. 1F), NSE (Fig. 1G) and CD56 (Fig. 1H) stains. CD117, CD34 and SMA stains were consistently negative. However, intervening fibroblasts in the lamina propria were positive for SMA. The hypertrophied muscle in the gall bladder wall was highlighted by SMA stain, while S100 stain brought out the hypertrophied nerve bundles in the myenteric plexus. Among the 500 cholecystectomy specimens reviewed, SCH-like lesions were identified in 20 of them (4%). These lesions were not observed during the original reporting. Three-quarters of SCH-like lesions were found in female patients and cholesterolosis was noted in 40% cases. This is the first time that SCH-like lesions is being reported in gall bladder mucosa. Similar lesions have been described in other parts of the GI tract either incidentally3Gibson J.A. Hornick J.L. Mucosal Schwann cell “hamartoma”: clinicopathologic study of 26 neural colorectal polyps distinct from neurofibromas and mucosal neuromas.Am J Surg Pathol. 2009; 33: 781-787Google Scholar or in association with ulcerative colitis.6Van Deen W.K. Hommes D.W. Mucosal Schwann cell hamartoma in ulcerative colitis: diagnosis and clinical relevance.Gastroenterol Hepatol. 2013; 9: 185-186Google Scholar Though the exact aetiology is not clear, SCH-like lesions may be the result of mechanical obstruction near the cystic duct as this lesion was commonly associated with neuromatoid hypertrophy of the inter-muscular nerve plexus. In addition, a possible link with a chronic inflammatory process cannot be ruled out. The immune-neural crosstalk has been implicated in the injury-activated neural proliferation response both in mammals and in invertebrate enteric nervous systems. Inflammation can also induce proliferation of LGR5-positive intestinal epithelial stem cells and their plasticity may help in regeneration and hypertrophy of nerve fibres in the GI tract.7Kizil C. Kyritsis N. Brand M. Effects of inflammation on stem cells: together they strive?.EMBO Rep. 2015; 16: 416-426Google Scholar Histologically, all SCH-like lesions in this cohort were restricted to the subepithelial mucosal region. Neural bundles in gall bladder mucosa have been described in association with neurofibromas,8Acebo E. Fernandez F.A. Val-Bernal J.F. Solitary neurofibroma of the gallbladder. A case report and review of the literature.Gen Diagn Pathol. 1998; 143: 337-340Google Scholar, 9Eggleston J.F. Goldman R.L. Neurofibroma and elastosis of the gallbladder. Report of an unusual case.Am J Gastroenterol. 1982; 77: 335-337Google Scholar schwannomas5Vandana U.G. Ravikala V.R. Dinesh U.S. Isolated polypoid ganglioneuroma of gall bladder – a case report.Al Ameen J Med Sci. 2011; 4: 295-298Google Scholar, 10Liu L.N. Xu H.X. Zheng S.G. et al.Solitary schwannomas of the gallbladder: a case report and literature review.World J Gastroenterol. 2014; 20: 6685-6690Google Scholar and ganglioneuromas,11Rehman A. Zuo C. Lee H. Sporadic ganglioneuroma of the gall bladder presenting as a mucosal polyp: report of an extremely rare case.Am J Clin Pathol. 2015; 144: A335Google Scholar, 12Odze R.D. Goldblum J.R. Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas.2nd ed. Saunders Elsevier, Philadelphia2009: 520Google Scholar which have distinctive morphological and IHC characteristics. Although SCH may resemble ganglioneuroma, the former does not show presence of ganglion cells.11Rehman A. Zuo C. Lee H. Sporadic ganglioneuroma of the gall bladder presenting as a mucosal polyp: report of an extremely rare case.Am J Clin Pathol. 2015; 144: A335Google Scholar, 12Odze R.D. Goldblum J.R. Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas.2nd ed. Saunders Elsevier, Philadelphia2009: 520Google Scholar In contrast to the diffuse positivity of S100 stain in SCH, neurofibromas show focal S100 positivity. While occasional positivity of CD34 stain is seen in a subset of stromal cells in neurofibromas, a similar pattern is not seen in SCH.2Namikawa T. Kawanishi Y. Fujieda Y. et al.Neurofibroma of the gallbladder not associated with neurofibromatosis.Surg Technol Int. 2016; 30: 89-92Google Scholar Schwannomas originating in the GI tract commonly present as mural nodules, consisting predominantly of cellular (Antoni A) areas and lacking a nuclear palisading pattern. They may histologically mimic other spindled nerve sheath tumours.9Eggleston J.F. Goldman R.L. Neurofibroma and elastosis of the gallbladder. Report of an unusual case.Am J Gastroenterol. 1982; 77: 335-337Google Scholar, 10Liu L.N. Xu H.X. Zheng S.G. et al.Solitary schwannomas of the gallbladder: a case report and literature review.World J Gastroenterol. 2014; 20: 6685-6690Google Scholar Colonic perineuriomas seen in female patients can also be considered as histological mimics of SCH, although the former show positivity for epithelial membrane antigen and are negative for S100 protein.9Eggleston J.F. Goldman R.L. Neurofibroma and elastosis of the gallbladder. Report of an unusual case.Am J Gastroenterol. 1982; 77: 335-337Google Scholar Other spindle cell lesions such as leiomyoma and gastrointestinal stromal tumour (GIST) should always be considered as differential diagnoses and were ruled out in this cohort of cases.9Eggleston J.F. Goldman R.L. Neurofibroma and elastosis of the gallbladder. Report of an unusual case.Am J Gastroenterol. 1982; 77: 335-337Google Scholar Defining morphological features of SCH seen in gall bladder and other areas of the GI tract are not yet described in available literature. However, as previously mentioned, SCH-like lesions in other parts of the GI tract usually present as polypoid mucosal lesions.3Gibson J.A. Hornick J.L. Mucosal Schwann cell “hamartoma”: clinicopathologic study of 26 neural colorectal polyps distinct from neurofibromas and mucosal neuromas.Am J Surg Pathol. 2009; 33: 781-787Google Scholar To summarise, SCH of gall bladder is an unreported mucosal hamartomatous spindle cell lesion, which can be confirmed by immunohistochemical staining. The real clinical significance of this lesion is not known. This article has been aimed at creating awareness on the presence of such lesions in gall bladder mucosa, so that they can be identified during routine reporting, which might disclose their clinical significance in the near future. We express our sincere thanks to all staff members of the department of Gastrointestinal Surgery for providing us the specimens for diagnostic work-up. The authors state that there are no conflicts of interest to disclose.