Title: Differential diagnosis of gastrointestinal stromal tumors versus leiomyomas by special
stains
Version: 6 Date: 11 Aug 2024
Reviewer:  Tomoyuki Otani
Reviewer's report:
This manuscript compares the histochemical characteristics of GISTs and gastrointestinal
leiomyomas. The main findings of this study are that GISTs are PAS-negative whereas
leiomyomas are PAS-positive, and that GISTs stain blue on MT whereas leiomyomas stain red
on MT. These staining techniques are widely used in laboratories around the world, and one
would think that if such a striking difference existed, it would have been reported by now; but
we can be surprised. However, some parts of the manuscript make one wonder whether this
study really happened.
Major comments:
1. How were the materials used for this study retrieved? Biopsy? Endoscopic resection? Surgical
resection? The method section states “All biopsy specimens were obtained by endoscopic
forceps” at one part and “All biopsy specimens were surgically resected by ESD or EMR”
at another. The declarations section states “The experimental material was derived from
pathological biopsy tissues”. The microphotographs provided do not look like those of biopsy
specimens (too large tissues).
2. Introduction and Discussions sections have some important statements that are not
presented in Results: “This is consistent with our research, for example, we found many
peritoneal tubercles were GISTs” (page 2; if this is from authors’ previous work, provide the
reference). “the morbidity were 34.2% (39/114) and 65.8% (75/114) in our current research,
respectively” (page 6).
3. Somewhat relevant, many parts are ambiguous as to whether the findings are those of the
present study or previous ones, or a general remark. For example, the Result section begins:
“GISTs and GILs may occur anywhere in the digestive system, and the clinical symptoms
were diverse from each other, for instance, several patients may feel difficulty in swallowing,
hemorrhage of digestive tract, chest pain et al, some even have no symptoms of discomfort.”
Does this describe the findings of the present study or a general remark? There are other instances
of such ambiguity in this manuscript.
4. The declarations section states “the experiment was repeated three times”. What is the exact
meaning of this statement? Did the authors stain the same tumor three times with the same
staining method?
5. AB-PAS staining of GISTs and leiomyomas are shown in Figures 3 and 4. The difference
in coloring between these two sets of photos seems to be too subtle to support the statement
that “all of the GISTs cases were PAS negative (light purple), and almost all GILs were PAS
positive (rose red) (P <0.01).” If the authors are confident of this statement, they could provide
a quantitative analysis.
6. Two GIST tissues used for MT staining (Figures 3D and G) look too sclerotic (abundant
collagen deposition and atrophic tumor cells) to be representative of GISTs. More typical-
looking tumors/regions should be shown to support the conclusion of the study.
7. This reviewer does not understand Figure 5.
Title: Differential diagnosis of gastrointestinal stromal tumors versus leiomyomas by special
stains
Version: 6 Date: 11 Aug 2024
Reviewer:  Tomoyuki Otani
Reviewer's report:
This manuscript compares the histochemical characteristics of GISTs and gastrointestinal
leiomyomas. The main findings of this study are that GISTs are PAS-negative whereas
leiomyomas are PAS-positive, and that GISTs stain blue on MT whereas leiomyomas stain red
on MT. These staining techniques are widely used in laboratories around the world, and one
would think that if such a striking difference existed, it would have been reported by now; but
we can be surprised. However, some parts of the manuscript make one wonder whether this
study really happened.
Major comments:
1. How were the materials used for this study retrieved? Biopsy? Endoscopic resection? Surgical
resection? The method section states “All biopsy specimens were obtained by endoscopic
forceps” at one part and “All biopsy specimens were surgically resected by ESD or EMR”
at another. The declarations section states “The experimental material was derived from
pathological biopsy tissues”. The microphotographs provided do not look like those of biopsy
specimens (too large tissues).
2. Introduction and Discussions sections have some important statements that are not
presented in Results: “This is consistent with our research, for example, we found many
peritoneal tubercles were GISTs” (page 2; if this is from authors’ previous work, provide the
reference). “the morbidity were 34.2% (39/114) and 65.8% (75/114) in our current research,
respectively” (page 6).
3. Somewhat relevant, many parts are ambiguous as to whether the findings are those of the
present study or previous ones, or a general remark. For example, the Result section begins:
“GISTs and GILs may occur anywhere in the digestive system, and the clinical symptoms
were diverse from each other, for instance, several patients may feel difficulty in swallowing,
hemorrhage of digestive tract, chest pain et al, some even have no symptoms of discomfort.”
Does this describe the findings of the present study or a general remark? There are other instances
of such ambiguity in this manuscript.
4. The declarations section states “the experiment was repeated three times”. What is the exact
meaning of this statement? Did the authors stain the same tumor three times with the same
staining method?
5. AB-PAS staining of GISTs and leiomyomas are shown in Figures 3 and 4. The difference
in coloring between these two sets of photos seems to be too subtle to support the statement
that “all of the GISTs cases were PAS negative (light purple), and almost all GILs were PAS
positive (rose red) (P <0.01).” If the authors are confident of this statement, they could provide
a quantitative analysis.
6. Two GIST tissues used for MT staining (Figures 3D and G) look too sclerotic (abundant
collagen deposition and atrophic tumor cells) to be representative of GISTs. More typical-
looking tumors/regions should be shown to support the conclusion of the study.
7. This reviewer does not understand Figure 5.
Please review this paper.
user
Title: Differential diagnosis of gastrointestinal stromal tumors versus leiomyomas by special
stains
Version: 6 Date: 11 Aug 2024
Reviewer:  Tomoyuki Otani
Reviewer's report:
This manuscript compares the histochemical characteristics of GISTs and gastrointestinal
leiomyomas. The main findings of this study are that GISTs are PAS-negative whereas
leiomyomas are PAS-positive, and that GISTs stain blue on MT whereas leiomyomas stain red
on MT. These staining techniques are widely used in laboratories around the world, and one
would think that if such a striking difference existed, it would have been reported by now; but
we can be surprised. However, some parts of the manuscript make one wonder whether this
study really happened.
Major comments:
1. How were the materials used for this study retrieved? Biopsy? Endoscopic resection? Surgical
resection? The method section states “All biopsy specimens were obtained by endoscopic
forceps” at one part and “All biopsy specimens were surgically resected by ESD or EMR”
at another. The declarations section states “The experimental material was derived from
pathological biopsy tissues”. The microphotographs provided do not look like those of biopsy
specimens (too large tissues).
2. Introduction and Discussions sections have some important statements that are not
presented in Results: “This is consistent with our research, for example, we found many
peritoneal tubercles were GISTs” (page 2; if this is from authors’ previous work, provide the
reference). “the morbidity were 34.2% (39/114) and 65.8% (75/114) in our current research,
respectively” (page 6).
3. Somewhat relevant, many parts are ambiguous as to whether the findings are those of the
present study or previous ones, or a general remark. For example, the Result section begins:
“GISTs and GILs may occur anywhere in the digestive system, and the clinical symptoms
were diverse from each other, for instance, several patients may feel difficulty in swallowing,
hemorrhage of digestive tract, chest pain et al, some even have no symptoms of discomfort.”
Does this describe the findings of the present study or a general remark? There are other instances
of such ambiguity in this manuscript.
4. The declarations section states “the experiment was repeated three times”. What is the exact
meaning of this statement? Did the authors stain the same tumor three times with the same
staining method?
5. AB-PAS staining of GISTs and leiomyomas are shown in Figures 3 and 4. The difference
in coloring between these two sets of photos seems to be too subtle to support the statement
that “all of the GISTs cases were PAS negative (light purple), and almost all GILs were PAS
positive (rose red) (P <0.01).” If the authors are confident of this statement, they could provide
a quantitative analysis.
6. Two GIST tissues used for MT staining (Figures 3D and G) look too sclerotic (abundant
collagen deposition and atrophic tumor cells) to be representative of GISTs. More typical-
looking tumors/regions should be shown to support the conclusion of the study.
7. This reviewer does not understand Figure 5.
assistant