Review for 10.1186/s12876-015-0349-4 (2015)

Reviewer's report
Title:Synchronous mucosal Schwann-cell hamartomas in a young adult as a
possible mucosal Schwann-cell harmatomatosis: a case report
Version:4Date:24 February 2015
Reviewer: Helen Remotti
Reviewer's report:
- Major Compulsory Revisions
1) In this case report, the presence of two separate neurogenic/schwannian
lesions (discrete diminutive polyp in mid rectum and a separate confluent region
in the distal rectum with polyposis) is a finding that has never been described for
“Schwann cell hamartomas”. Although not reported for gastrointestinal schwann
cell hamartomas, such cases have been reported for gastrointestinal mucosal
neuromas/neurofibromas.
The term “Schwann cell hamartoma” was created to describe a unique diagnostic
group of neurogenic mucosal polyps that are not associated with hereditary
cancer associated syndromes, in contrast to neuromas or ganglioneuromas that
may be associated with a hereditary cancer syndromes such as
neurofibromatosis type I (NF1) or multiple endocrine neoplasia 2B (MEN2B[1,2].
From a practical point of view, the terms mucosal neuroma, and schwannian
hamartoma are identical lesions. A ganglioneuroma is essentially the same
lesion with the presence of ganglion cells. It is important to note that histologically
the same polyp occurring in a specific clinical setting, such as in syndromic
patients (example NF1 patients) are usually classified as mucosal neuromas and
not schwannian hamartomas.
In this case report in view of the unique endoscopic findings (multiple polyps), the
lesions are probably most appropriately termed mucosal neuromas. Isolated
case reports have been reported in which patients are diagnosed endoscopically
with multiple neurogenic polyps (mucosal neurofibromas, mucosal neuromas) in
the absence of associated systemic syndromes, similar to this case presentation.
[3,4]
2) Irregardless of the diagnostic term used to classify the neurogenic polyps,
particularly if numerous polyps are present, all such patients should be clinically
evaluated for hereditary syndromes, which include consultation with a clinical
geneticist.
The authors only tested peripheral blood ‘analyzing exomes of NF1 and RET
genes ’. On p6, lines 14-16, the authors state ”we confirmed the absence of
germline mutations in the NF1 gene and in the RET gene by Sanger sequencing
of leukocyte DNA.” The authors should give limitations on the methodology used
to test germline mutations in the peripheral blood. How sensitive is exome
sequencing in detecting cases of NF1 and MEN2B? Even in patients with
diagnostic clinical features of NF-1, exome sequencing will not detect a certain
proportion of cases – what percentages are missed?
With regard to genetic testing for NF-1 and RET gene mutations, it is important
that the concept of genetic mosaicism be addressed[5]. In view of the presence
of multiple polyps with a region of the distal rectum showing polyposis, a
thorough clinical evaluation and molecular genetic evaluation of the polyps are
required, since it is well recognized that in certain syndromes such as NF-1,
patients with mosaic NF1 can only be established by comprehensive screening
of the lesional tissue.[6, Maertens, 2007 #4] It is well recognized that the
percentage of NF-1 mutation in non-neural crest derived cells in NF1 patients
with somatic mosaicism is so low that it would be missed by routing NF1
screening of blood.[5] Additional testing of the patient’s polyps would be needed
to evaluate possible association with genetic syndromes. Such testing would
greatly strengthen this case report.
3) Background: lines 13-15 Sentence is not clear. Schwannomas of the GI tract
usually involve the muscularis propria and are not mucosal polyps.
Schwannomas may have Verocay bodies, Antoni A… …and lymphoid cuffs,
neuromas which have axons. (Recommend separate sentence addressing
features of neuromas). Mucosal neuromas in syndromic patients (MEN2B and
NF1) may be identical morphologically to Schwann cell hamartomas occurring in
non-syndromic patients. Gibson, et. al. also found that NFP (neuron filament
protein) highlighted rare axons in 7 mucosal schwannomas, with all other
markers (GFAP, EMA, claudin-1 CD34, SMA and KIT) being negative. In 5
neurofibromas from known NF-1 patients studied, all contained scattered NFP
positive axons and were positive for S100, but showed more intralesional
heterogeneity. The authors concluded distinguishing the two lesions is difficult
based on both histologic features or immunohistochemical profiles.[1]
4) Case Presentation: The histologic description of the polyps describes
“plexiform proliferation of spindle cells in the lamina propria, which was
intervened the adjacent crypts”- English should be edited.
This description however does not describe the superficial discrete nodular
growth pattern of the spindle cells. It is difficult in the photo to assess how deep
these nodules extend into the mucosa, particularly if the reach the level of the
muscularis mucosae. Based on the H&E photos of the polyps the S100 positive
component of the polyp consists of cohesive dense aggregates or nodules that
predominantly involve the superficial lamina propria. This pattern is fairly unique.
Typically schwannian hamartomas show a more diffuse pattern of infiltration
within the lamina propria with S100 positive spindle cells extending between
crypts. It is important to mention that as described by Gibson, mucosal
schwannomas show a diffuse proliferation of S100 spindle cells within the lamina
propria. In this case report the presence of nodular aggregates and focal
plexiform arrangement of S100 positive cells is a feature more typical of
neuroma/neurofibroma.
5) Case Presentation: (p5 line 2) As stated in the case report, the mother and
grandfather had colorectal carcinoma. It would be important to know the age at
which they were diagnosed. (If tumor tissue could be evaluated, it may be of
interest to analyze the mother’s tumor tissue, particularly for NF-1 mutations) To
date, there is limited association with colorectal carcinoma and
ganglioneuromatosis, limited to several case reports.
1. Gibson JA, Hornick JL (2009) Mucosal Schwann cell "hamartoma":
clinicopathologic study of 26 neural colorectal polyps distinct from neurofibromas
and mucosal neuromas. Am J Surg Pathol 33: 781-787.
2. Rittershaus AC, Appelman HD (2011) Benign gastrointestinal mesenchymal
BUMPS: a brief review of some spindle cell polyps with published names. Arch
Pathol Lab Med 135: 1311-1319.
3. Carter JE, Laurini JA (2008) Isolated intestinal neurofibromatous proliferations
in the absence of associated systemic syndromes. World J Gastroenterol 14:
6569-6571.
4. Agaimy A, Vassos N, Croner RS (2012) Gastrointestinal manifestations of
neurofibromatosis type 1 (Recklinghausen's disease): clinicopathological
spectrum with pathogenetic considerations. Int J Clin Exp Pathol 5: 852-862.
5. Kehrer-Sawatzki H, Cooper DN (2008) Mosaicism in sporadic
neurofibromatosis type 1: variations on a theme common to other hereditary
cancer syndromes? J Med Genet 45: 622-631.
6. Beert E, Brems H, Renard M, Ferreiro JF, Melotte C, et al. (2012) Biallelic
inactivation of NF1 in a sporadic plexiform neurofibroma. Genes Chromosomes
Cancer 51: 852-857.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.