JC-2015-DH10 (December)

-Contains a monthly selection of articles from the top medical and dermatology journals. (Prof. JH Saurat M.D.)
-To view the abstracts, please click on the link at the top of the 1st post. This redirects you to the journal of the matching issue.

When Treating a Skin Rash for Years, think of Skin lymphoma…

Postby CFH » Thu Nov 05, 2015 12:26 pm

TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL.
Kirsch IR, Watanabe R, O’Malley JT, Williamson DW, Scott LL, Elco CP, Teague JE, Gehad A, Lowry EL, LeBoeuf NR, Krueger JG, Robins HS, Kupper TS, Clark RA.
Sci Transl Med. 2015 Oct 7;7(308):308ra158. doi: 10.1126/scitranslmed.aaa9122.



Diagnosis of cutaneous T-Cell lymphoma (CTCL) is often delayed by many years (6 on average) after being often treated as eczema and other benign inflammatory diseases. Early diagnosis allows the patient to know prognosis and to begin an effective treatment.

CTCL is initially confined to the skin for many years. Then, the abnormal cells may eventually infiltrate other tissues including blood, lymph nodes, lungs, heart, liver and spleen. skin only is involved. To detect this skin biopsies need to confirm the suspicion followed by radiological imaging….effective treatment potentially requiring to be systemic.

Detection of a malignant T cell clone is critical in making the diagnosis of CTCL, but the T cell receptor γ (TCRγ) polymerase chain reaction (PCR) analysis in current clinical use detects clones in only a subset of patients.


In the following study from Boston done on skin biopsies:

High-throughput TCR sequencing (HTS) detected T cell clones in 46 of 46 (100%) CTCL patients
-This was more sensitive and specific than TCRγ PCR, and allowed to dedifferentiate CTCL from benign inflammatory diseases.
-HTS was also accurate to measure disease activity (response to treatments, recurrence)


Early spread in the bloodstrean for lesions apparently only limited to the skin HTS allows to detect small number of malignant T-Cells – this has direct pronostical and therapeutic implications.
The study also brings new understanding of CTCL.

1. Indeed, analysis of CTCL TCRγ genes shows that CTCL is a malignancy derived from mature T cells:
-Normally, there is a maximum amount (density) of T-cells in benign inflammatory lesions.
-This density is exceeded in CTCL
–Conclusion: There is a niche of finite size may exist for benign T cells in skin.

2. Immunostaining shows that malignant CTCL T cells staying in the skin and those disseminating in the bloodstream are localized to different anatomic compartments in the skin.

Conclusion:
-HTS allows diagnosis of all stages of CTCL and can excludes from benign inflammatory diseases
-HTS also brings new developments in the understanding of the CTCL



A brief reminder of lymphomas and Cutaneous T-Cell lymphoma (CTCL)
-Lymphomas are the result of involvement of the skin of tumors of lymph nodes and lymphatic system. Lymphomas are tumors of the lymph nodes and lymphatic system.
-Extranodal lymphomas are tumors that occur in organs or tissues outside of the lymphatic system. When lymphomas occur in the skin with no evidence of disease anywhere else at the time of diagnosis, they are called ‘primary’ cutaneous lymphomas.
-There are many different types of primary cutaneous lymphomas but they can be broadly divided into two categories, cutaneous T-cell lymphomas (CTCL) and cutaneous B-cell lymphomas. Of all primary cutaneous lymphomas, 65% are of the T-cell type.

-Classification is regularly updated. The most recent one (at time of publication) is the result of a consensus between the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer Classification (EORTC). It can be found from the link HERE

No treatment brings a cure but lesions can disappear.

There are many treatments available:
They include topical steroids, caryolysine, Extracorporeal photopheresis as well as systemic agents such as : Bexarotene (Targretin; a retinoid Denileukin diftitox (Ontak); Vorinostat (Zolinza; a hydroxymate histone deacetylase (HDAC) inhibitor); Romidepsin (Istodax) a cyclic peptide histone deacetylase (HDAC) inhibitor)

CFH
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JC-2015-DH10 (December)

Postby CFH » Wed Jan 13, 2016 10:03 am

http://www.dermatologicahelvetica.com/e ... clesID=120 (Page 4)

1-Oral Nicotinamide reduces the rates of new nonmelanoma skin cancers

2-Vulvar Lichen Sclerosus: less cancers when well managed

3-Genomic variants in the EGFR pathway that predispose to skin rash and better survival after EGFR inhibitors

4-Lesion-directed screening has a similar cancer detection rate to total body examination.

5-Topical retinoids evoke neurogenic inflammation

6-Eccrine sweat glands are much closer to sebaceous glands than previously thought
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