Is it Possible to Obtain Immunofluorescence Data in Formalin-Fixed Paraffin-Embedded Skin Samples for the Diagnosis of Pemphigus Vulgaris and Bullous Pemphigoid.

OBJECTIVE: The gold-standard method for assessment of autoimmune bullous disease is direct/indirect immunofluorescence (IF) examination applied to fresh frozen tissue. Since the sensitivity of IF is greatly reduced in formalin-fixed paraffin-embedded (FFPE) tissues, IF cannot be relied upon in these samples. However, immunohistochemistry with the C4d antibody is a promising marker used as a surrogate for immune complex deposition, in nephropathology practice, and the paraffin IF method is also used as a `salvage` technique when fresh frozen tissue is not available or lacks glomeruli. We aimed to investigate whether it is possible to obtain immunofluorescence data from FFPE tissues diagnosed with bullous pemphigoid (BP) and pemphigus vulgaris (PV) and its relationship with inflammatory parameters in the skin. MATERIAL AND METHODS: Eighty-nine in-house cases with both IgG and C3 positivity by routine immunofluorescence examination were included in the study. Inflammation parameters were evaluated in hematoxylin-eosin sections. Immunofluorescence study with IgG protease digestion and C4d immunohistochemistry were performed. RESULTS: Results of 83 biopsies were obtained by paraffin immunofluorescence with IgG. There were positive reactions in 28 (34%) of these 83 biopsies. Five of the 28 positive results belonged to BP (18%), and 23 were PV (82%). Ten positive results were on lesional skin (36%), and 18 (64%) were on non-lesional skin. In the immunohistochemical study with C4d, 84 biopsy results were obtained. There were positive reactions in 34 (40.4%) of 84 biopsies. Of the 34 positive results, 12 belonged to BP (35.3%) and 22 to PV (64.7%). Again, 22 (64.7%) of 34 positive results belonged to lesional skin, and 12 (35.3%) belonged to non-lesional skin. When both techniques were used together, 44 (54%) of 81 biopsies yielded positive results for at least one of the two studies, while in 37 (46%), both tests showed negative results. CONCLUSION: The sensitivity of both IgG and C4d was less than in the literature, especially in BP-diagnosed biopsies. Positive samples were mostly PV. In conclusion, obtaining immunofluorescence data in FFPE samples is possible and is independent of the related skin being lesional or not, however, negative results should not be relied upon.

Teriflunomide-Induced Palmoplantar Pustular Psoriasis: Case Report and Review of the Literature.

Teriflunomide is a once-daily oral immunomodulatory disease-modifying treatment for multiple sclerosis (MS). Skin reactions are an infrequent side effect of teriflunomide. Here, we present the case of a 52-year-old female patient with ankylosing spondylitis who was consulted for demyelinating lesions and limb weakness. She was diagnosed with multiple sclerosis and started treatment with teriflunomide. Palmoplantar pustular psoriasis developed after three weeks of treatment initiation. It is a rare side effect related to teriflunomide.

Stromal or intraepithelial tumor-infiltrating lymphocytes: which one has more prognostic significance in cervical cancer?

PURPOSE: To investigate the effect of tumor-infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) on treatment results in patients with cervical squamous cell carcinoma who underwent definitive or adjuvant radiotherapy (RT) or chemoradiotherapy (CRT). METHODS: Pathological specimens were evaluated from 96 cervical cancer patients who were treated with definitive or adjuvant RT/CRT between April 2001 and January 2020. The percentage of intraepithelial TILs (iTILs) and stromal TILs (sTILs) were calculated, and immunohistochemistry was used for identifying lymphocyte lineage with CD4, CD8, and CD20 antibodies and macrophages with CD68 antibody. Prognostic values of TILs/TAMs on oncological outcomes were evaluated. RESULTS: Thirty patients had early-stage disease and 66 patients had advanced-stage disease. Sixty-three and 33 patients received adjuvant RT and definitive CRT, respectively. Low number of sCD20 positive cells was associated with large tumor size and parametrial invasion. In multivariate analysis, low percentage of sTILs and advanced-stage disease were independent poor prognostic factors for overall survival, disease-free survival (DFS), and distant metastasis-free survival; low number of sCD4 positive cells was also an independent poor prognostic factor for DFS. Low percentage of sTILs and low number of sCD8 positive cells was correlated with high rates of distant metastasis (p = 0.038 and p = 0.025, respectively). CONCLUSION: sTILs have superior predictive value than iTILs in terms of prognosis. Stromal compartment should be investigated as a routine practice in TIL studies in cervical cancer. Intensifying the treatment in cervical cancer patients with low number of sTILs should be studied in further investigations.

Clonal B-cell proliferations developing in the background of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder: A case series.

Clonal B-cell proliferations and B-cell lymphomas may co-occur in the background of follicular helper T-cell (TFH)-derived lymphomas, most associated with EBV, which has been a well-known fact for many years in the prototypical entity "TFH lymphoma, angioimmunoblastic-type." Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+ PCSM-LPD) is also a TFH-derived clonal proliferation. We searched the archives and identified four cases of CD4+ PCSM-LPD with accompanying clonal B-cell proliferation (one of which showed EBER positivity), and one longstanding case of CD4+ PCSM-LPD, in the background of which a B-cell lymphoma had developed. These five cases broaden experience on CD4+ PCSM-LPD with accompanying B-cell proliferations and also support routine evaluation of these cases with EBV in situ hybridization, to better determine whether or not there is an association with EBV.