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PostScript
Neuromuscular and vascular hamartoma: is it a true hamartoma? Neuromuscular and vascular hamartoma (NMVH) is a very rare gastrointestinal tract lesion. Twenty NMVH cases have been published in the English literature since its first description by Fernando and McGovern in 1982.1 There is no age or gender predilection for NMVH. The clinical presentations of NMVH patients are usually non-specific, including chronic abdominal pain, intermittent bowel obstruction, occult bleeding and iron deficiency anaemia. Three of the 20 reported
284
J Clin Pathol March 2014 Vol 67 No 3
Downloaded from http://jcp.bmj.com/ on May 31, 2015 - Published by group.bmj.com
PostScript cases were incidental findings on CT scan or colonoscopy. Radiologically, the involved bowel may demonstrate a stricture with thickened walls, intussusception, or a polypoid mass. All but one case occurred in the small bowel. The two NMVH cases we reported here also showed non-specific clinical and radiologic features. The first patient came to our institute for evaluation of over 1 year of intermittent abdominal pain. She had a history of anaemia and arthritis. Her workup included abdominal and pelvic CT scans, sub-sequential small bowel follow through and antegrade doubleballoon enteroscope, which suggested intussusception without obstruction and a long intraluminal lipomatous lesion of the
mid-ileum. The lesion was resected. Our second patient had multiple medical problems and several surgeries in the past. An incidental pedunculated polyp at terminal ileum was revealed at a routine screening colonoscopy. The lesion was biopsied and showed prominent smooth muscle that was initially interpreted as consistent with leiomyoma. A right hemicolectomy was performed and three polypoid mass lesions were identified. Grossly, NMVH may occur as single or multiple strictures that affect a variable length of the bowel, or as a single or multiple polypoid mass lesions. Hemmings2 reported a 4.5 cm Merkel’s diverticulum with a 0.9 cm area of NMVH-like changes. A case of diffuse filiform
polyposis was reported by Oakley et al.3 Our two cases reported here demonstrated single or multiple polypoid lesions. The cut surfaces were smooth tan-yellow with abundant adipose tissue (figure 1A). Histologically, NMVH is mainly composed of disorganised fascicles of smooth muscle, bundles of non-myelinated nerve fibres with scattered abnormal ganglion cells and hemangiomatous vascular channels (figure 2). These features were found in both our cases (figure 1B–D). Fatty infiltration of submucosal tissue reported previously4 was also shown in our current two cases. In our second case, abundant dilated lymphatic channels were present in the mucosa and submucosa mixed with other mesenchymal components (figure
Figure 1 (A) Neuromuscular and vascular hamartoma, gross picture demonstrates a polypoid mass lesion with tan-yellow and lobulated cut surfaces. H&E stains show (B) mucosal and submucosal proliferation of smooth muscle fascicles, blood vessels, nerve and adipose tissue (×2 magnification), (C) Smooth muscle fibres and abnormal vessels (×20 magnification), (D) adipose tissue mixed with nerve bundles and vessels (×20 magnification), (E) smooth muscle fibres disarray and dilated lymphovascular channels (×10 magnification), and (F) mucosal pseudopyloric metaplasia (×10 magnification). J Clin Pathol March 2014 Vol 67 No 3
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PostScript
Figure 2 Distribution of histologic features of the 20 reported neuromuscular and vascular hamartoma cases. 1E). Subsequently, immunohistochemical stains were performed to highlight different mesenchymal components in our cases. Smooth muscle actin stained haphazardly arranged smooth muscle bundles predominately originating from muscularis mucosa, as well as thick-walled blood vessels (figure 3A). CD34 showed numerous mucosal and submucosal small and large blood vessels (figure 3B). Nerve
bundles, as well as naked ganglion cells, were highlighted by S-100 (figure 3C). CD117 stained scattered mast cells (figure 3D). Several non-specific histological findings have been observed in the reported NMVH cases (figure 2). Mucosal ulceration is frequently seen above or near the area of NMVH. Inflammatory infiltrations with predominantly lymphocytes and plasma cells are often present.
Pseudopyloric metaplasia has also been reported. In our cases, focal surface ulceration with non-specific acute/chronic inflammation and pseudopyloric metaplasia were found in one of the lesions (figure 1F). Given that similar histological features may be seen in Crohn’s disease or diaphragm disease of the small bowel, the hamartomatous nature of NMVH has been argued.5–7 Some of the features related to Crohn’s disease, including areas of mucosal cobblestone appearance and lymph node granulomata, were reported in five of the 20 NMVH cases (figure 2), in which three patients had prior history of Crohn’s disease. It is worth noting that the most fundamental histological features in Crohn’s disease are transmural chronic inflammation, deep fissuring and noncaseating granuloma. In the advanced stages, neuromuscular hypertrophy, as well as submucosal and serosal fibrosis, are frequent, which contribute to the occurrence of stenosis/stricture. All the aforementioned hallmarks of Crohn’s disease were absent in our two cases and most of the reported NMVH cases (figure 2). Therefore, it is unlikely that the NMVH is part of the spectrum of pathological presentation of Crohn’s disease. Diaphragm disease was first thoroughly described in 1988 by Lang et al8 and was thought to be associated with long-term
Figure 3 Immunohistochemistry stains show different mesenchymal components: (A) Smooth muscle actin (SMA) demonstrates disorganised fascicles of smooth muscles with intermixed abnormal blood vessels (×20 magnification); (B) CD34 shows numerous thin and thick-walled blood vessels (×10 magnification); (C) S100 highlights disorganised non-myelinated nerve bundles and ganglion cells (×20 magnification); (D) CD117 stains scattered mast cells but not the spindle cells (×20 magnification). 286
J Clin Pathol March 2014 Vol 67 No 3
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PostScript use of non-steroidal anti-inflammatory drugs (NSAID). The bowel resections usually reveal multiple thin, web-like mucosal septa that project into the lumen (diaphragmatic narrowing). The lesion is histologically characterised by mucosal superficial ulceration and associated prominent submucosal fibrosis. Three reports argued that NMVH and diaphragm disease were indistinguishable since their histologic features were similar (figure 2). To identify the disease entity of the cases we reported, we studied our cases and the published NMVH and diaphragm disease cases. Prominent fibrosis, the histological hallmark of diaphragm disease described by Lang et al8 was not present in our two cases nor in 15 of the 20 reported NMVH cases (figure 2). Prominent submucosal fibrosis that is present in ischaemia was not seen in the first NMVH case reported by Fernando and McGovern1 who attributed the submucosal thickening to the presence of large numbers of smooth muscle cells that were noted ultrasturcturally. The history of using NSAIDs may be helpful but not a reliable feature to discriminate diaphragm disease from NMVH. Our two patients had history of NSAIDs use, but their lesions did not show histological features of diaphragm disease. Thus, NMVH is likely a distinct disease entity that is different from diaphragm disease. Our cases demonstrated rare small bowel polypoid lesions with histologic features of NMVH, which could not be attributed to other reactive conditions. ‘Neuromesenchymal hamartoma’ proposed by Salas et al4 may be a more appropriate term to replace NMVH as a diagnostic entity to include broader histological characteristics.
Bing Ren, Wenqing Cao Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA Correspondence to Dr Wenqing Cao, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, Rochester, NY 14642, USA; wenqing_cao@URMC. Rochester.edu Contributors Design: WC; writing: WC, BR; material: BR, WC; overall: WC, BR. Competing interests None. Ethics approval Ethics approval was provided by University of Rochester. Provenance and peer review Not commissioned; externally peer reviewed. To cite Ren B, Cao W. J Clin Pathol 2014;67:284– 287. Received 18 August 2013 Revised 13 October 2013 Accepted 20 October 2013 Published Online First 21 November 2013 J Clin Pathol 2014;67:284–287. doi:10.1136/jclinpath-2013-201913
REFERENCES 1 2
3
4
5
6
7
Take-home messages ▸ Neuromuscular and vascular hamartoma (NMVH) is a rare hamartomatous lesion that commonly occurs in the small bowel and may present as stricture or a polypoid mass. ▸ NMVH clinically and pathologically mimics Crohn’s disease, diaphragm disease and other reactive conditions. ▸ A diagnosis of NMVH depends on histopathology and should be diagnosed with caution if the patient is taking NSAIDs or has clinical history of Crohn’s disease.
J Clin Pathol March 2014 Vol 67 No 3
8
Fernando SS, McGovern VJ. Neuromuscular and vascular hamartoma of small bowel. Gut 1982;23:1008–12. Hemmings CT. Neuromuscular and vascular hamartoma arising in a Meckel’s diverticulum. Pathology 2006;38:173–4. Oakley GJ 3rd, Schraut WH, Peel R, et al. Diffuse filiform polyposis with unique histology mimicking familial adenomatous polyposis in a patient without inflammatory bowel disease. Arch Pathol Lab Med 2007;131:1821–4. Salas A, Casellas F, Sanz J, et al. Neuromesenchymal hamartoma of the small bowel. J Clin Gastroenterol 1990;12:705–9. Shepherd NA, Jass JR. Neuromuscular and vascular hamartoma of the small intestine: is it Crohn’s disease? Gut 1987;28:1663–8. Cortina G, Wren S, Armstrong B, et al. Clinical and pathologic overlap in nonsteroidal anti-inflammatory drug-related small bowel diaphragm disease and the neuromuscular and vascular hamartoma of the small bowel. Am J Surg Pathol 1999;23:1414–17. de Sanctis S, Qureshi T, Stebbing JF. Clinical and pathological overlap in nonsteroidal anti-inflammatory drug-related small bowel diaphragm disease and the neuromuscular and vascular hamartoma of the small bowel. Am J Surg Pathol 2001;25:539–41. Lang J, Price AB, Levi AJ, et al. Diaphragm disease: pathology of disease of the small intestine induced by non-steroidal anti-inflammatory drugs. J Clin Pathol 1988;41:516–26.
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Neuromuscular and vascular hamartoma: is it a true hamartoma? Bing Ren and Wenqing Cao J Clin Pathol 2014 67: 284-287 originally published online November 21, 2013
doi: 10.1136/jclinpath-2013-201913 Updated information and services can be found at: http://jcp.bmj.com/content/67/3/284
These include:
References Email alerting service
This article cites 8 articles, 3 of which you can access for free at: http://jcp.bmj.com/content/67/3/284#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
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PostScript
Neuromuscular and vascular hamartoma: is it a true hamartoma? Neuromuscular and vascular hamartoma (NMVH) is a very rare gastrointestinal tract lesion. Twenty NMVH cases have been published in the English literature since its first description by Fernando and McGovern in 1982.1 There is no age or gender predilection for NMVH. The clinical presentations of NMVH patients are usually non-specific, including chronic abdominal pain, intermittent bowel obstruction, occult bleeding and iron deficiency anaemia. Three of the 20 reported
284
J Clin Pathol March 2014 Vol 67 No 3
Downloaded from http://jcp.bmj.com/ on May 31, 2015 - Published by group.bmj.com
PostScript cases were incidental findings on CT scan or colonoscopy. Radiologically, the involved bowel may demonstrate a stricture with thickened walls, intussusception, or a polypoid mass. All but one case occurred in the small bowel. The two NMVH cases we reported here also showed non-specific clinical and radiologic features. The first patient came to our institute for evaluation of over 1 year of intermittent abdominal pain. She had a history of anaemia and arthritis. Her workup included abdominal and pelvic CT scans, sub-sequential small bowel follow through and antegrade doubleballoon enteroscope, which suggested intussusception without obstruction and a long intraluminal lipomatous lesion of the
mid-ileum. The lesion was resected. Our second patient had multiple medical problems and several surgeries in the past. An incidental pedunculated polyp at terminal ileum was revealed at a routine screening colonoscopy. The lesion was biopsied and showed prominent smooth muscle that was initially interpreted as consistent with leiomyoma. A right hemicolectomy was performed and three polypoid mass lesions were identified. Grossly, NMVH may occur as single or multiple strictures that affect a variable length of the bowel, or as a single or multiple polypoid mass lesions. Hemmings2 reported a 4.5 cm Merkel’s diverticulum with a 0.9 cm area of NMVH-like changes. A case of diffuse filiform
polyposis was reported by Oakley et al.3 Our two cases reported here demonstrated single or multiple polypoid lesions. The cut surfaces were smooth tan-yellow with abundant adipose tissue (figure 1A). Histologically, NMVH is mainly composed of disorganised fascicles of smooth muscle, bundles of non-myelinated nerve fibres with scattered abnormal ganglion cells and hemangiomatous vascular channels (figure 2). These features were found in both our cases (figure 1B–D). Fatty infiltration of submucosal tissue reported previously4 was also shown in our current two cases. In our second case, abundant dilated lymphatic channels were present in the mucosa and submucosa mixed with other mesenchymal components (figure
Figure 1 (A) Neuromuscular and vascular hamartoma, gross picture demonstrates a polypoid mass lesion with tan-yellow and lobulated cut surfaces. H&E stains show (B) mucosal and submucosal proliferation of smooth muscle fascicles, blood vessels, nerve and adipose tissue (×2 magnification), (C) Smooth muscle fibres and abnormal vessels (×20 magnification), (D) adipose tissue mixed with nerve bundles and vessels (×20 magnification), (E) smooth muscle fibres disarray and dilated lymphovascular channels (×10 magnification), and (F) mucosal pseudopyloric metaplasia (×10 magnification). J Clin Pathol March 2014 Vol 67 No 3
285
Downloaded from http://jcp.bmj.com/ on May 31, 2015 - Published by group.bmj.com
PostScript
Figure 2 Distribution of histologic features of the 20 reported neuromuscular and vascular hamartoma cases. 1E). Subsequently, immunohistochemical stains were performed to highlight different mesenchymal components in our cases. Smooth muscle actin stained haphazardly arranged smooth muscle bundles predominately originating from muscularis mucosa, as well as thick-walled blood vessels (figure 3A). CD34 showed numerous mucosal and submucosal small and large blood vessels (figure 3B). Nerve
bundles, as well as naked ganglion cells, were highlighted by S-100 (figure 3C). CD117 stained scattered mast cells (figure 3D). Several non-specific histological findings have been observed in the reported NMVH cases (figure 2). Mucosal ulceration is frequently seen above or near the area of NMVH. Inflammatory infiltrations with predominantly lymphocytes and plasma cells are often present.
Pseudopyloric metaplasia has also been reported. In our cases, focal surface ulceration with non-specific acute/chronic inflammation and pseudopyloric metaplasia were found in one of the lesions (figure 1F). Given that similar histological features may be seen in Crohn’s disease or diaphragm disease of the small bowel, the hamartomatous nature of NMVH has been argued.5–7 Some of the features related to Crohn’s disease, including areas of mucosal cobblestone appearance and lymph node granulomata, were reported in five of the 20 NMVH cases (figure 2), in which three patients had prior history of Crohn’s disease. It is worth noting that the most fundamental histological features in Crohn’s disease are transmural chronic inflammation, deep fissuring and noncaseating granuloma. In the advanced stages, neuromuscular hypertrophy, as well as submucosal and serosal fibrosis, are frequent, which contribute to the occurrence of stenosis/stricture. All the aforementioned hallmarks of Crohn’s disease were absent in our two cases and most of the reported NMVH cases (figure 2). Therefore, it is unlikely that the NMVH is part of the spectrum of pathological presentation of Crohn’s disease. Diaphragm disease was first thoroughly described in 1988 by Lang et al8 and was thought to be associated with long-term
Figure 3 Immunohistochemistry stains show different mesenchymal components: (A) Smooth muscle actin (SMA) demonstrates disorganised fascicles of smooth muscles with intermixed abnormal blood vessels (×20 magnification); (B) CD34 shows numerous thin and thick-walled blood vessels (×10 magnification); (C) S100 highlights disorganised non-myelinated nerve bundles and ganglion cells (×20 magnification); (D) CD117 stains scattered mast cells but not the spindle cells (×20 magnification). 286
J Clin Pathol March 2014 Vol 67 No 3
Downloaded from http://jcp.bmj.com/ on May 31, 2015 - Published by group.bmj.com
PostScript use of non-steroidal anti-inflammatory drugs (NSAID). The bowel resections usually reveal multiple thin, web-like mucosal septa that project into the lumen (diaphragmatic narrowing). The lesion is histologically characterised by mucosal superficial ulceration and associated prominent submucosal fibrosis. Three reports argued that NMVH and diaphragm disease were indistinguishable since their histologic features were similar (figure 2). To identify the disease entity of the cases we reported, we studied our cases and the published NMVH and diaphragm disease cases. Prominent fibrosis, the histological hallmark of diaphragm disease described by Lang et al8 was not present in our two cases nor in 15 of the 20 reported NMVH cases (figure 2). Prominent submucosal fibrosis that is present in ischaemia was not seen in the first NMVH case reported by Fernando and McGovern1 who attributed the submucosal thickening to the presence of large numbers of smooth muscle cells that were noted ultrasturcturally. The history of using NSAIDs may be helpful but not a reliable feature to discriminate diaphragm disease from NMVH. Our two patients had history of NSAIDs use, but their lesions did not show histological features of diaphragm disease. Thus, NMVH is likely a distinct disease entity that is different from diaphragm disease. Our cases demonstrated rare small bowel polypoid lesions with histologic features of NMVH, which could not be attributed to other reactive conditions. ‘Neuromesenchymal hamartoma’ proposed by Salas et al4 may be a more appropriate term to replace NMVH as a diagnostic entity to include broader histological characteristics.
Bing Ren, Wenqing Cao Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA Correspondence to Dr Wenqing Cao, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, Rochester, NY 14642, USA; wenqing_cao@URMC. Rochester.edu Contributors Design: WC; writing: WC, BR; material: BR, WC; overall: WC, BR. Competing interests None. Ethics approval Ethics approval was provided by University of Rochester. Provenance and peer review Not commissioned; externally peer reviewed. To cite Ren B, Cao W. J Clin Pathol 2014;67:284– 287. Received 18 August 2013 Revised 13 October 2013 Accepted 20 October 2013 Published Online First 21 November 2013 J Clin Pathol 2014;67:284–287. doi:10.1136/jclinpath-2013-201913
REFERENCES 1 2
3
4
5
6
7
Take-home messages ▸ Neuromuscular and vascular hamartoma (NMVH) is a rare hamartomatous lesion that commonly occurs in the small bowel and may present as stricture or a polypoid mass. ▸ NMVH clinically and pathologically mimics Crohn’s disease, diaphragm disease and other reactive conditions. ▸ A diagnosis of NMVH depends on histopathology and should be diagnosed with caution if the patient is taking NSAIDs or has clinical history of Crohn’s disease.
J Clin Pathol March 2014 Vol 67 No 3
8
Fernando SS, McGovern VJ. Neuromuscular and vascular hamartoma of small bowel. Gut 1982;23:1008–12. Hemmings CT. Neuromuscular and vascular hamartoma arising in a Meckel’s diverticulum. Pathology 2006;38:173–4. Oakley GJ 3rd, Schraut WH, Peel R, et al. Diffuse filiform polyposis with unique histology mimicking familial adenomatous polyposis in a patient without inflammatory bowel disease. Arch Pathol Lab Med 2007;131:1821–4. Salas A, Casellas F, Sanz J, et al. Neuromesenchymal hamartoma of the small bowel. J Clin Gastroenterol 1990;12:705–9. Shepherd NA, Jass JR. Neuromuscular and vascular hamartoma of the small intestine: is it Crohn’s disease? Gut 1987;28:1663–8. Cortina G, Wren S, Armstrong B, et al. Clinical and pathologic overlap in nonsteroidal anti-inflammatory drug-related small bowel diaphragm disease and the neuromuscular and vascular hamartoma of the small bowel. Am J Surg Pathol 1999;23:1414–17. de Sanctis S, Qureshi T, Stebbing JF. Clinical and pathological overlap in nonsteroidal anti-inflammatory drug-related small bowel diaphragm disease and the neuromuscular and vascular hamartoma of the small bowel. Am J Surg Pathol 2001;25:539–41. Lang J, Price AB, Levi AJ, et al. Diaphragm disease: pathology of disease of the small intestine induced by non-steroidal anti-inflammatory drugs. J Clin Pathol 1988;41:516–26.
287
Downloaded from http://jcp.bmj.com/ on May 31, 2015 - Published by group.bmj.com
Neuromuscular and vascular hamartoma: is it a true hamartoma? Bing Ren and Wenqing Cao J Clin Pathol 2014 67: 284-287 originally published online November 21, 2013
doi: 10.1136/jclinpath-2013-201913 Updated information and services can be found at: http://jcp.bmj.com/content/67/3/284
These include:
References Email alerting service
This article cites 8 articles, 3 of which you can access for free at: http://jcp.bmj.com/content/67/3/284#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
