Primary Cutaneous Gamma-Delta T-Cell Lymphoma Initially Diagnosed as Subcutaneous Panniculitis-like T-Cell Lymphoma with Dermatomyositis
, Masahiko Ohsawa 4 and Daisuke Tsuruta 1Round 1
Reviewer 1 Report
Straightforward case report of CGD-TCL. However, it is a good reminder of the diagnostic pitfall shared with SPTCL. The apparent indolent course (albeit only 1 year follow-up) and association with dermatomyositis would also be interesting to the reader.
43: Restate as "and an apparent indolent course".
45: Was the patient previously already diagnosed with dermatomyositis? If so, this should be clarified by rephrasing as "female with a known case of dermatomyositis for a year". Also good to indicate if malignancy screening was performed, and any findings (just a brief sentence will suffice).
45: "presenting with" rather than "presented with".
49: Comment if B symptoms (fever, night sweats, weight loss) present.
51: "muscle strength grade 3 of 5" rather than "3/5 of normal muscle strength".
52: Elaborate which extremities (i.e. upper/lower, proximal/distal).
62: Remove "consistent with dermatomyositis". To me, the muscle biopsy at most only suggests myositis.
66: Is L26 the same as CD20? If so, saying CD20 would be easier understood.
67: Is TCR rearrangement monoclonal or polyclonal? Please indicate.
95-99: Is this relevant to the case report? Can omit.
114: Were they any similar characteristics between this case and others with indolent behavior reported in the literature (e.g. were their immunophenotypes similar)? If so, will be good to mention and discuss.
117: Qualify by stating "the disease appears to be indolent".
121: At this juncture, it will be good to also discuss the association between dermatomyositis and malignancies, particularly during periods of exacerbation, as this case report highlights.
124: Can the authors apply recognized diagnostic criteria (e.g. EULAR/ACR Classification) and see whether diagnosis of dermatomyositis is still unconfirmed?
129: Re-phrase as "More CGD-TCL studies will help to elucidate".
133: Instead of "upper extremities", indicate the specific body part depicted in the photograph.
Author Response
Reviewer #1:
Straightforward case report of CGD-TCL. However, it is a good reminder of the diagnostic pitfall shared with SPTCL. The apparent indolent course (albeit only 1 year follow-up) and association with dermatomyositis would also be interesting to the reader.
We are very pleased to hear this favorable comment. Thank you very much for reviewing our manuscript.
43: Restate as "and an apparent indolent course".
According to the reviewer’s suggestion, we have restated as "and an apparent indolent course". Thank you for the suggestion.
45: Was the patient previously already diagnosed with dermatomyositis? If so, this should be clarified by rephrasing as "female with a known case of dermatomyositis for a year". Also good to indicate if malignancy screening was performed, and any findings (just a brief sentence will suffice).
The patient was previously already diagnosed with dermatomyositis. This is now clarified by rephrasing as "female with a known case of dermatomyositis for a year". No malignancy was reported before the visiting. The sentence is now included. Thank you for the suggestion.
45: "presenting with" rather than "presented with".
According to the reviewer’s suggestion, the sentence is now corrected. Thank you for the suggestion.
49: Comment if B symptoms (fever, night sweats, weight loss) present.
No B symptoms (fever, night sweats, weight loss) were observed. The comment is included in the revised manuscript. Thank you for the suggestion.
51: "muscle strength grade 3 of 5" rather than "3/5 of normal muscle strength".
According to the reviewer’s suggestion, the sentence is now corrected. Thank you for the suggestion.
52: Elaborate which extremities (i.e. upper/lower, proximal/distal).
Proximal upper and proximal lower limbs were affected. It is now indicated in the revised manuscript. Thank you for the suggestion.
62: Remove "consistent with dermatomyositis". To me, the muscle biopsy at most only suggests myositis.
According to the reviewer’s suggestion, the sentence is now removed. Thank you for the suggestion.
66: Is L26 the same as CD20? If so, saying CD20 would be easier understood.
According to the reviewer’s suggestion, L26 is now corrected as CD20. Thank you for the suggestion.
67: Is TCR rearrangement monoclonal or polyclonal? Please indicate.
It is monoclonal. It is now indicated. Thank you for the suggestion.
95-99: Is this relevant to the case report? Can omit.
According to the reviewer’s suggestion, it is deleted.
114: Were they any similar characteristics between this case and others with indolent behavior reported in the literature (e.g. were their immunophenotypes similar)? If so, will be good to mention and discuss.
Similarly to our case, those cases responded very well to treatment with either multiagent chemotherapy or prednisone. We have emphasized the sentence written in the original manuscript.
117: Qualify by stating "the disease appears to be indolent".
The expression is now corrected. Thank you for the suggestion.
121: At this juncture, it will be good to also discuss the association between dermatomyositis and malignancies, particularly during periods of exacerbation, as this case report highlights.
A study suggested that the highest risk for malignancy is seen in the first year after dermatomyositis diagnosis (Tudorancea et al Curr Health Sci 2021; 4:377-382). However, the association between dermatomyositis and malignancies during periods of exacerbation is unknown. These statements are now included in the revised manuscript. Thank you for the suggestion.
124: Can the authors apply recognized diagnostic criteria (e.g. EULAR/ACR Classification) and see whether diagnosis of dermatomyositis is still unconfirmed?
We can not confirm the diagnosis of dermatomyositis from clinical record by applying the recognized diagnostic criteria.
129: Re-phrase as "More CGD-TCL studies will help to elucidate".
The expression is now corrected. Thank you for the suggestion.
133: Instead of "upper extremities", indicate the specific body part depicted in the photograph.
It is now corrected as “brachium.” Thank you for the suggestion.
Reviewer 2 Report
My comment about this case report
This case might be a gamma/delta T-cell lymphoma (GDTCL)co-existing with dermatomyositis, which is value for publication. However, the authors should be clarified about following points
- Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) has been misdiagnosed initially, since immunohistochemistry (IHC) study was not complete . According to WHO classification of skin tumor 2018, the diagnosis of SPTCL should be base on CD8+ with alpha/beta T-cell phenotype. Expressing gamma/ delta T-cell receptor is excluded. The diagnosis of SPTCL cannot be based on only IHC for CD3, CD4, CD8, granzyme B, L26 and CD56. This might be confused the reader that this case was initially SPTCL and switch to GDTCL.
- In addition, the results of T-cell receptor gene rearrangement should be indicated which T-cell receptor gene shows positive clonal rearrangement.
- EBV-encoded RNA in situ hybridization should be performed in this case, because extranodal NK/T-cell lymphoma, nasal type (ENKTCL) can be presented with a subcutaneous panniculitis -like lymphoma. ENKTCL cannot be excluded from the differential diagnosis by only negative CD56. In some cases of ENKTCL can be found negative CD56 and positive CD8.
- CD8+ in GDTCL can be found in rare cases, even though this is an uncommon phenotype. This point should be raised to caution when interpretate of IHC.
- The clinical figures are very nice; however, for the microscopic figures, the brightness and white balance should be corrected. In addition, magnifications of the figure should be added in the figure legend. Higher power of basal vacuolar change might be added in figure 2. For IHC labelling, adding the white background might be made these labelling clearer.
- It will be interesting if the discussion session will add more about types of cutaneous lymphoma, which has been reported co-existing with dermatomyositis
Author Response
Reviewer #2: This case might be a gamma/delta T-cell lymphoma (GDTCL)co-existing with dermatomyositis, which is value for publication. However, the authors should be clarified about following points
We are very pleased to hear this favorable comment. Thank you very much for reviewing our manuscript.
1. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) has been misdiagnosed initially, since immunohistochemistry (IHC) study was not complete. According to WHO classification of skin tumor 2018, the diagnosis of SPTCL should be base on CD8+ with alpha/beta T-cell phenotype. Expressing gamma/ delta T-cell receptor is excluded. The diagnosis of SPTCL cannot be based on only IHC for CD3, CD4, CD8, granzyme B, L26 and CD56. This might be confused the reader that this case was initially SPTCL and switch to GDTCL.
We agree that SPTCL has been misdiagnosed initially, because it was more than ten years ago and WHO classification of skin tumor 2018 was not applied. We have recently reassessed the case and corrected the diagnosis.
2. In addition, the results of T-cell receptor gene rearrangement should be indicated which T-cell receptor gene shows positive clonal rearrangement.
Jg and Cb of T-cell receptor gene showed positive clonal rearrangement. It is now described in the manuscript. Thank you for the suggestion.
3. EBV-encoded RNA in situ hybridization should be performed in this case, because extranodal NK/T-cell lymphoma, nasal type (ENKTCL) can be presented with a subcutaneous panniculitis -like lymphoma. ENKTCL cannot be excluded from the differential diagnosis by only negative CD56. In some cases of ENKTCL can be found negative CD56 and positive CD8.
Negative result of EBV-encoded RNA in situ hybridization was reported in this case. Although we described the result in the revised manuscript, we could not obtain and show the data of more than ten years ago.
4. CD8+ in GDTCL can be found in rare cases, even though this is an uncommon phenotype. This point should be raised to caution when interpretate of IHC.
CD8 expression was observed in our case. CD8+ in rare cases of GDTCL is now indicated in the discussion part of the manuscript. Thank you for the suggestion.
5. The clinical figures are very nice; however, for the microscopic figures, the brightness and white balance should be corrected. In addition, magnifications of the figure should be added in the figure legend. Higher power of basal vacuolar change might be added in figure 2. For IHC labelling, adding the white background might be made these labelling clearer.
According to the reviewer’s suggestion, brightness and white balance are corrected. Magnifications of the figure are added in the figure legend. Higher power of basal vacuolar change is added in figure 2. For IHC labelling, white background is made for IHC labelling. Thank you for the suggestion.
6. It will be interesting if the discussion session will add more about types of cutaneous lymphoma, which has been reported co-existing with dermatomyositis.
It is also reported that the prevalence of non-Hodgkin lymphoma is highest in hematopoietic malignancies (Tudorancea et al Curr Health Sci 2021; 4:377-382). This sentence is now included in the discussion part (L121) of the revised manuscript. Thank you for the suggestion.
Round 2
Reviewer 1 Report
18 - change "L-26" to "CD20"
47 - change "visiting" to "visit"
123 - add heliotrope "rash"
143 - change "L-26" to "CD20"
Author Response
Reviewer #1:
Comments and Suggestions for Authors
18 - change "L-26" to "CD20"
47 - change "visiting" to "visit"
123 - add heliotrope "rash"
143 - change "L-26" to "CD20"
Thank you very much for reviewing our manuscript.
According to the suggestion, the above points were corrected.
Reviewer 2 Report
I do have a few comments on the revised manuscript as follow:
1. Please, check the sequence of description of figure 2. The description in the manuscript is not corresponded with the figure 2, since 2B is lobular panniculitis with rimming with atypical lymphoid cells and2D is basal vacuolar change. The authors can change the figure according to sequence of description or vice versa.
2. I suggested for the description of immunohistochemistry of figure 3 in the manuscript as follow: “the atypical lymphoid cells were positive for CD3, CD8, granzyme-B, and delta-TCR, but they did not mark with CD20, CD4, CD56 and beta-F1 (figure 3)” instead of “ which, expressed CD3+, CD4-, CD8+,granzymeB+, CD20-, CD56- (figure 3)”.
3. Could the authors add figure of EBV in situ hybridization in figure 3 in the blank area? If it is not possible, the authors can change the arrangement to 2x4 instead of 3x3. In addition, magnification of the immunohistochemistry should be added in the figure legend.
4. I understand that this patient initially diagnosed as SPTCL base on classification of WHO classification 2008, since on that time the immunohistochemistry for gamma TCR or delta TCR were not applied and also the diagnostic criteria on that period. I think it might be clearer to the reader if the authors clarify the timeline of initial diagnosis and the recent diagnosis
Author Response
Reviewer #2: Comments and Suggestions for Authors
I do have a few comments on the revised manuscript as follow:
Thank you very much for reviewing our manuscript again.
- Please, check the sequence of description of figure 2. The description in the manuscript is not corresponded with the figure 2, since 2B is lobular panniculitis with rimming with atypical lymphoid cells and2D is basal vacuolar change. The authors can change the figure according to sequence of description or vice versa.
According to the reviewer’s suggestion, the sequence of description is now corrected. Thank you for the suggestion.
- I suggested for the description of immunohistochemistry of figure 3 in the manuscript as follow: “the atypical lymphoid cells were positive for CD3, CD8, granzyme-B, and delta-TCR, but they did not mark with CD20, CD4, CD56 and beta-F1 (figure 3)” instead of “ which, expressed CD3+, CD4-, CD8+,granzymeB+, CD20-, CD56- (figure 3)”.
According to the reviewer’s suggestion, the description is now corrected. Thank you for the suggestion.
- Could the authors add figure of EBV in situ hybridization in figure 3 in the blank area? If it is not possible, the authors can change the arrangement to 2x4 instead of 3x3. In addition, magnification of the immunohistochemistry should be added in the figure legend.
We do not have images of EBV in situ hybridization. The magnification of the immunohistochemistry is added in the figure legend. Thank you for the suggestion.
- I understand that this patient initially diagnosed as SPTCL base on classification of WHO classification 2008, since on that time the immunohistochemistry for gamma TCR or delta TCR were not applied and also the diagnostic criteria on that period. I think it might be clearer to the reader if the authors clarify the timeline of initial diagnosis and the recent diagnosis
The patient visited our department in 2011. The patient initially diagnosed as SPTCL base on the 2008 WHO classification. In 2020, we performed immunohistochemistry on skin samples. And, we corrected the initial diagnosis of SPTCL to a diagnosis of CGD-TCL based on the 2018 WHO classification. This issue is now addressed in the revised manuscript. Thank you for the suggestion.
