Collision of Basal Cell Carcinoma with Apocrine–Sebaceous–Follicular Unit Neoplasms

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The interesting paper reports on Basal cell carcinoma that are in with collision with  Apocrine-Sebaceous-Follicular unit tumors.

Some changes should improve the paper.

The title would read more precise: “Collision of Basal Cell Carcinoma with Apocrine-Sebaceous-Follicular Unit Tumors and Cysts”.

The lack of collision of SCC and AFSu should be mentioned in the abstract

To the best of our knowledge, this report describes …

Better: Our collective also suggests that immunosuppression could be a factor that predisposes collisions

All figures: Start the legend with the diagnosis

Figure 3 better description: Steatocystoma shows a cutícula and a corrugated surface with a thinned stratum granulosum.

Figure 4 shows two separate cases, confusing, split in two figures

Sentence is not understandable: The pale squamous tumor borders for a thick basal membrane corresponds to a tricholemmoma.

Case 11: Better Another field shows a clear-cut BCC

Page 15, not understandable: BerEP4 was positive in all BCC and negative for the ASFu neoplasms but the clear cells of the clear cell hidradenoma and focally in the tricholemmomas.

Page 15, Curiously, SMA was positive in 5 out of 7 BCC, ..

Table 3, Case 1, …. No  bold letters

Table 4 ASMA instead of actina

Table 4, last line, translate “uFSA: Unidad Foliculo-sebácea-apocrina”

Discussion

Page 17, delete the names in the sentence …….with dermatofibromas.4, 26 (Boyd, Requena)

Page 17, second-to-last line, again ASMA instead of actina

Page 18, This study has some limitations. In spite of our files contain 23.265 biopsies, only 12 BCC collisions and no SCC collision were retrieved.

Comments on the Quality of English Language

English correction and editing by a native speaker seem mandatory

Author Response

Revisor 1

 1.- The title would read more precise: “Collision of Basal Cell Carcinoma with Apocrine-Sebaceous-Follicular Unit Tumors and Cysts”.

I have changed the title to “Collision of Basal Cell Carcinoma with Apocrine–Sebaceous–Follicular Unit Neoplasms”. Most of the referencial books of apocrine, eccrine, sebaceous and follicular neoplasms include the cysts in the contens, but not in the title. It is true that they are not true tumors, but they are neoplasm. So, I have changed the title.

Requena et al. Neoplasm with Apocrine Differentiaton. 1^st ed. Philadelphia: Lippincott-Raven; 1998.

Steffen et al. Neoplasms with Sebaceous Differentation. 1^st ed. Philadelphia. Lea & Febiger; 1994.

Ackerman et al- Neoplasm with follicular Differntation. 1^st ed.  Philadelphia. Lea & Febiger; 1993.

Abenoza et al. Neoplasm with eccrine Differentation. 1^st ed. Philadelphia. Lea & Febiger; 1990.

Nevertheless, I have specifically clarified that the cysts were included in the study.   

2.- The lack of collision of SCC and AFSu should be mentioned in the abstract

I Have rewritten the abstract, and this point has been mentioned.

3.- To the best of our knowledge, this report describes …

Better: Our collective also suggests that immunosuppression could be a factor that predisposes collisions

The text have completely reviewed  

4.- All figures: Start the legend with the diagnosis

I have added the diagnosis in all figures

5.- Figure 3 better description: Steatocystoma shows a cutícula and a corrugated surface with a thinned stratum granulosum.

Although, I have changed some points in the text of the figure 3. I not clearly appreciate a stratum granulosum in the picture.  Although, it is an usual finding in steatocystomas, in some cases is not appreciate because the pressure.

6.- Figure 4 shows two separate cases, confusing, split in two figures

The figures illustrate the collision not the case. However, I reassure that the number of case of each picture is indicates.

7.- Sentence is not understandable: The pale squamous tumor borders for a thick basal membrane corresponds to a tricholemmoma.

The text and English grammar have been reviewed.

8.- Case 11: Better Another field shows a clear-cut

Unfortunately, the process of the sample was not adecuate to show in the same sample the collision. I Know is not the best picture to illustrated this collision, but I have not better photographies

9.- Page 15, not understandable: BerEP4 was positive in all BCC and negative for the ASFu neoplasms but the clear cells of the clear cell hidradenoma and focally in the tricholemmomas.

Page 15, Curiously, SMA was positive in 5 out of 7 BCC, ..

The text and English grammar have been reviewed.

9.- Table 3, Case 1, …. No  bold letters

I’ ve changed

10.- Table 4 ASMA instead of actina

I`ve changed

11.- Table 4, last line, translate “uFSA: Unidad Foliculo-sebácea-apocrina”

I’ve changed 

12.- Page 17, delete the names in the sentence …….with dermatofibromas.4, 26 (Boyd, Requena)

I’ve deleted

13.- Page 17, second-to-last line, again ASMA instead of actina

I’ve changed

14.- Page  18, This study has some limitations. In spite of our files contain 23.265 biopsies, only 12 BCC collisions and no SCC collision were retrieved.

 The text and English grammar have been reviewed.

15.- Comments on the Quality of English Language

English correction and editing by a native speaker seem mandatory

The text and English grammar have been reviewed by english reviewer with experience in scientific language.

Comment: Thank you for your revision. I feel that the manuscript has been improved with your suggestions.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for the chance to review this interesting research regarding collisions between basal cell carcinomas and tumors of the apocrine-sebaceous-follicular unit.

Extensive review of the English language, there are some “Spanishicisms” as Unidad Foliculo-sebácea-apocrina (abbreviation of Table 4), and of the punctuation is needed.

Introduction:

-   “Excluding in situ squamous cell carcinoma (SCC) and its variants. basal cell carcinoma (BCC) is the most frequent skin malignancy, representing the 70% of them.” Check after “variants”.

Material and methods:

-  “CKA1/A3” is CK AE1/AE3. Check also Table 1.

Results:

- “After reviewing, we excluded 11 because: a) the tumors were separated and therefore, not in collision (3 cases); b) in addition to the BCC the only finding was a foreign body granuloma to keratin (3 cases); c) there were ductal or follicular dilatations but not big enough to be considered a cyst by us (6 cases)” 3+3+6 = 12, and not 11. Thus, how many cases were included and excluded, respectively?

- In figure 3 the putative tumor in collision should be a steatocystoma. In the sections for immunohistochemistry is possible to see the small sebaceous lobule connected to the cystic structure, but at the HE it is difficult to interpret the lesion as a steatocystoma. The histopathological clue for the diagnosis of this entity is the presence of a wavy, eosinophilic cuticle in the internal aspect of the wall of the cyst, which is absent in this case. Please provide a representative picture for this case.

Discussion:

- “Although currently, most authors consider collisions as a casual event, Some theories have been proposed to explain collisions25: a) A casual incidence of two common entites; b) a common trigger as actinic damage that is related with BCC, SCC and melanoma; may favor the apparition of collisions among them; c) induction from the stroma of one neoplasm may predispose to the apparition of the new one, in a similar way to what happens with dermatofibromas.4, 26 (Boyd, Requena) d) a hybrid neoplastic cell that has retained properties from different line cells. However, we propose some new factors that may influence the occurrence of collisions: 1) Although in discussion, most authors consider BCC derivates from/differentiates toward follicular germinative cells; hence, the common embryological origin of ASFu could explain the results of our study27, 28. 2) According to our results, immunosuppression state could favor collisions. 25% to 33% of our cases were immunosuppressed, c) Finally, a common genetic or molecular basis may promote the apparition of some different tumors. BCC may share genetic alterations with some ASFu in this case29,30”. Please check the punctuation. Authors of the references cited are also reported in parentheses (Boyd, Requena).

Figures:

- Please provide higher quality images. All the pictures are very dark, especially those stained with HE.

Comments on the Quality of English Language

Extensive review of the English language, there are some “Spanishicisms” as Unidad Foliculo-sebácea-apocrina (abbreviation of Table 4), and of the punctuation is needed.

Author Response

Revisor 2

1.- Extensive review of the English language, there are some “Spanishicisms” as Unidad Foliculo-sebácea-apocrina (abbreviation of Table 4), and of the punctuation is needed.

The text and English grammar have been reviewed by english reviewer with experience in scientific language

2.- Introduction:

- “Excluding in situ squamous cell carcinoma (SCC) and its variants. basal cell carcinoma (BCC) is the most frequent skin malignancy, representing the 70% of them.” Check after “variants”.

I.ve changed the text

3.- Material and methods:

- “CKA1/A3” is CK AE1/AE3. Check also Table 1.

I’ve changed

4.- Results:

- “After reviewing, we excluded 11 because: a) the tumors were separated and therefore, not in collision (3 cases); b) in addition to the BCC the only finding was a foreign body granuloma to keratin (3 cases); c) there were ductal or follicular dilatations but not big enough to be considered a cyst by us (6 cases)” 3+3+6 = 12, and not 11. Thus, how many cases were included and excluded, respectively?

I agree with you. There was a mistake. I’ve corrected

5.- In figure 3 the putative tumor in collision should be a steatocystoma. In the sections for immunohistochemistry is possible to see the small sebaceous lobule connected to the cystic structure, but at the HE it is difficult to interpret the lesion as a steatocystoma. The histopathological clue for the diagnosis of this entity is the presence of a wavy, eosinophilic cuticle in the internal aspect of the wall of the cyst, which is absent in this case. Please provide a representative picture for this case.

I’ve added a panoramic H&E figure were the cyst is connected with a sebaceous lobule. However, in my opinion figure 3b (before 3a) shows a cuticule. It is not corrugated because the pressure but to my clear enough.  

6.- Discussion:

- “Although currently, most authors consider collisions as a casual event, Some theories have been proposed to explain collisions25: a) A casual incidence of two common entites; b) a common trigger as actinic damage that is related with BCC, SCC and melanoma; may favor the apparition of collisions among them; c) induction from the stroma of one neoplasm may predispose to the apparition of the new one, in a similar way to what happens with dermatofibromas.4, 26 (Boyd, Requena) d) a hybrid neoplastic cell that has retained properties from different line cells. However, we propose some new factors that may influence the occurrence of collisions: 1) Although in discussion, most authors consider BCC derivates from/differentiates toward follicular germinative cells; hence, the common embryological origin of ASFu could explain the results of our study27, 28. 2) According to our results, immunosuppression state could favor collisions. 25% to 33% of our cases were immunosuppressed, c) Finally, a common genetic or molecular basis may promote the apparition of some different tumors. BCC may share genetic alterations with some ASFu in this case29,30”. Please check the punctuation. Authors of the references cited are also reported in parentheses (Boyd, Requena).

I’ve deleted the name of authors. The text and English grammar have been reviewed

7.- Figures:

- Please provide higher quality images. All the pictures are very dark, especially those stained with HE.

Althoug, I feel the pictures are clear enough. I’ve checked my collection of photographies of the cases and all pictures are similar in brghtness and contrast.  

8.- Comments on the Quality of English Language

Extensive review of the English language, there are some “Spanishicisms” as Unidad Foliculo-sebácea-apocrina (abbreviation of Table 4), and of the punctuation is needed.

The text and English grammar have been reviewed by english reviewer with experience in scientific language. So, the english language have been improved.

Reviewer 3 Report

Comments and Suggestions for Authors

I have read the article with great interest. However, I have some comments:

A.     Abstract:

• Needs better structure…
• You should add “Background-Objective” before “Materias+Methods-Results-Discussion” and make each entity more visually evident
• Please add that you conducted a retrospective study
• “To the best of our knowledge. This report describes…” please paraphrase
•  Please be more specific with your results eg ASFu beneath BCC = 8/12 patients etc

B.     Main:

• Introduction: please paraphrase the first paragraph and be more specific with the definitions eg in situ SCC and its variants?, because it can be confusing.
• Also «because in our experience we thought that BCC-ASFu tumors association was more frequent than random» Not  scientific term
• “collisions of tumors, including BCC collisions, are casual” please paraphrase
• In Material and methods you state that: “Nevertheless, for us is” please be specific on who Us is. Please paraphrase and make more clear the 2 definitions of collision tumors
• Table 2: please fix grammar and spelling mistakes
• Page 17: «According to our results, immunosuppression state could favor collisions. 25% to 33% of our cases were immunosuppressed», I do not believe that with these data and the small number of patients (3/12) we should make such generalization and associate immunosuppression with collision tumors… it is a hypothesis that cannot be proved.
• Page 18: «Although it is a retrospective study, most cases have been recently diagnosed. It could be because our interest in collisions grew since 2010 when we presented a series in a meeting.» please paraphrase and be more specific
•  Page 18:«All cases of our series are big enough to be considered cysts without doubt.» please paraphrase

Overall this article can be improved with some amendments.

Pay close attention to spelling and grammar throughout the entire article.

Comments on the Quality of English Language

Pay close attention to spelling and grammar throughout the entire article.

Author Response

Revisor 3

1.- A. Abstract:

• Needs better structure…

You should add “Background-Objective” before “Materias+Methods-Results-Discussion” and make each entity more visually evident

• Please add that you conducted a retrospective study
• “To the best of our knowledge. This report describes…” please paraphrase
• Please be more specific with your results eg ASFu beneath BCC = 8/12 patients etc

I’ve rewritten the abstract. I’ve added the sections according you suggestions. And the english have been reviewed

2.- B. Main:

• Introduction: please paraphrase the first paragraph and be more specific with the definitions eg in situ SCC and its variants?, because it can be confusing.

I’ve tried to explain the variants of SCC to make the text more understandable

3.- Also «because in our experience we thought that BCC-ASFu tumors association was more frequent than random» Not  scientific term

• “collisions of tumors, including BCC collisions, are casual” please paraphrase

I’ve check the text, as well as, the english grammar.

•  In Material and methods you state that: “Nevertheless, for us is” please be specific on who Us is. Please paraphrase and make more clear the 2 definitions of collision tumors

I’ve changed this mistake. I am the ony author. I’ve changed all the text in this aspect. Now, I think it is clear enough.  

4.- Table 2: please fix grammar and spelling mistakes

I’ve done

5.- Page 17: «According to our results, immunosuppression state could favor collisions. 25% to 33% of our cases were immunosuppressed», I do not believe that with these data and the small number of patients (3/12) we should make such generalization and associate immunosuppression with collision tumors… it is a hypothesis that cannot be proved.

The series is too small to strong conclusions. The text say “could favor” and in the conclusions I specify that “the conclusions have to be considered with caution”.But I think that I’ve to mentioned this hypothesis because, in spite of the small number of cases 25 to 33% were immunosuppressed.

6.- ·       Page 18: «Although it is a retrospective study, most cases have been recently diagnosed. It could be because our interest in collisions grew since 2010 when we presented a series in a meeting.» please paraphrase and be more specific

• Page 18:«All cases of our series are big enough to be considered cysts without doubt.» please paraphrase

The text and English grammar have been reviewed by english reviewer with experience in scientific language. So, the english language have been improved.

7.- Overall this article can be improved with some amendments.

Pay close attention to spelling and grammar throughout the entire article.

Comments on the Quality of English Language

Pay close attention to spelling and grammar throughout the entire article.

The text and English grammar have been reviewed by english reviewer with experience in scientific language. So, the english language have been improved.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The quality of the text has been improved.