Preliminary results on a proposed histopathological assessment of predictive factors for basal cell carcinoma recurrence after primary free margin excision.

Background: Basal cell carcinoma (BCC) incidence is steadily increasing but therapeutic solutions remain limited and present a public health challenge. Aims: To identify predictive factors of BCC recurrence after primary free margin excision, with automated methods, by evaluating cell proliferation, the Hedgehog pathway activation and primary cilia. Materials and Methods: This case-control study included 32 patients (16 with recurrence occurring at least 6 months after complete resection, and 16 without recurrence) who underwent surgery for BCC. Formalin-fixed paraffin-embedded cutaneous resections were processed for immunohistochemistry or immunostaining with the following primary antibodies: mouse anti-MCM6, rabbit anti-ARL13B and rabbit anti-GLI1. Results: BCC recurrence after free margin excision was significantly linked to a higher proliferative index (p < 0.001) and a lower cilia count (p = 0.041) in the primary lesion. No significant differences were observed regarding cilia length (p = 0.39) or GLI1-positive nuclei. Discussion: The complex interplay between essential signaling pathways, cell proliferation and cilia requires further experimental investigations in the context of BCC recurrence. Conclusion: A higher proliferative index evaluated with MCM6 antibody could be a useful prognosis marker of BCC risk of recurrence. The lower cilia count in the primary lesion unveiled novel perspectives to understand BCC recurrence molecular mechanisms.

[Impact of positive surgical margins on prostate cancer prognosis]. / Impact carcinologique des marges positives après prostatectomie totale.

OBJECTIVE: To examine the impact of positive surgical margins (PSM) after radical prostatectomy (RP) for prostate cancer on oncological results. PATIENTS AND METHODS: We performed a study where all patients who underwent radical prostatectomy between January 2004 and December 2018 for prostate cancer were included. The preoperative, postoperative data and the carcinological results collected were analyzed. Data were analysed using Kaplan-Meier survival analysis and proportional hazards models. RESULTS: A total of 319 patients with a median age of 65 years (IQR : 62-69) were included. The median follow-up was 43.6 months (IQR: 19.4-79.3). The overall rate of PSM was 33.5%. PSM was associated with biochemical recurrence (P<0.001). Overall mortality was not associated with positive margins. A clinical stage> T1c was an independent predictor of PSM on multivariate analysis (P=0.01). CONCLUSION: PSM would increase the risk of biochemical recurrence with no impact on survival. Clinical stage>T1c was an adverse predictor for PSM. LEVEL OF EVIDENCE: 3.

Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry.

BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.

Efficacy and safety of panitumumab alone or in association with radiotherapy in unresectable cutaneous squamous cell carcinoma.

BACKGROUND: The prognosis of unresectable cutaneous squamous cell carcinomas is very poor. OBJECTIVE: To evaluate the efficacy and safety of panitumumab alone or in association with radiotherapy in the treatment of unresectable cutaneous squamous cell carcinoma. METHODS: This was a monocentre retrospective study of all consecutive patients having received at least two courses of panitumumab, alone or in association with radiotherapy, between 2016 and 2019. The primary endpoint was the rate of best overall response, evaluated according to the RECIST 1.1 criteria. The secondary endpoints were the response and disease control rates at 6 weeks and 6 months, progression-free survival, overall survival and safety. RESULTS: A total of 25 patients were included; their median age was 86 years, and 17 (86%) had a WHO performance status over 2. The best overall response rate was 52%, including four complete responses (16%) and nine partial responses (36%). All patients with complete response and five out of nine patients with partial response had received concurrent radiotherapy, in most cases in moderate to low doses (<40 Gray, 67%). The response rates at 6 weeks and 6 months were 12% and 28%, respectively. The control rates at 6 weeks and 6 months were 84% and 32%, respectively. Median progression-free survival was 6.9 months, and median overall survival was 10.5 months. Grade 3 side-effects, mostly dermatological, occurred in 16 patients (64%). CONCLUSION: These results suggest that panitumumab remains pertinent in the treatment of unresectable cutaneous squamous cell carcinoma, in particular in association with radiotherapy, despite recent advances with anti-PD-1 antibodies. It presents several advantages: it can be used in very elderly or feeble patients, it does not provoke anaphylactic or other irreversible or life-threatening side-effects, and our study observed some long-term responses. Further prospective investigation of anti-EGFR antibodies, in association with anti-PD-1 antibodies and/or chemotherapy, should be conducted.

[Interest of reTURB for pTa high grade bladder urothelial carcinoma]. / Intérêt de la résection complémentaire (ou « second look ¼) pour les carcinomes urothéliaux de vessie classés pTa haut grade.

INTRODUCTION: Second look TURB (Transurethral Resection of Bladder Tumor) is recommended for high-risk pT1 tumors. It is well acquired for tumors classified pT1 high grade but its interest is still discussed for high-grade pTa tumors in the absence of high level of evidence. We evaluated the impact of second-look resection for the high-grade pTa bladder tumor. METHODS: We performed a retrospective study in 2 centers from 2007 to 2016. We included all urothelial tumors classified pTa high grade. We studied the anatomopathological findings of reTURB and its consequences on survival without recurrence and progression. RESULTS: Eighty-four patients were included. Thirty-five patients (41.7%) had reTURB and residual tumor was found in 42.9% of cases. The anatomopathology of reTURB was in 20% of cases high grade pTa, in 14.3% of cases pTis, and in 8.6% of cases pT1. Forty-three patients had recurrence, 13 reTURB patients (30.2%). In the patients who had a reTURB, 12 had recurrence (34.3%) against 31 without reTURB, (63.3%). After the first TURB, 45 patients (53.6%) had bladder instillation: 38 received BCG (45.2%) and 7 ametycin (8.3%). The main factor decreasing recurrence was BCG adjuvant therapy (HR=0.4 [0.2-0.9], P=0.02). The absence of reRTUV appeared to be a recurrence factor, but the result was not statistically significant (HR=1.4 [0.7-3], P=0.3). CONCLUSION: reTURB confirms that residual tumor is often found. His interest in survival without recurrence remains to be proved by a prospective study with a larger number of patients. LEVEL OF EVIDENCE: 3.

Prurigo pigmentosa in a fair-skinned European woman: Dramatic improvement with doxycycline.

INTRODUCTION: Prurigo pigmentosa is a rare inflammatory, pruriginous skin disease seen predominantly in young Asian women, with average age of onset in the mid-20s. OBSERVATION: A 25-year-old fair-skinned European woman presented with a two-year history of pruriginous skin lesions recurring fortnightly. The initial lesions were inflammatory papules, which first emerged on the back of the neck before spreading to the shoulders, below the breasts and the back. The papules resolved leaving a reticular hyperpigmented network that gradually worsened after each episode. The clinical presentation and histopathological findings were consistent with a diagnosis of prurigo pigmentosa. Doxycycline 200mg/day was initiated, with rapid resolution, absence of any further flare-ups and gradual regression of the reticular pigmentation. DISCUSSION: Prurigo pigmentosa is a skin disease of stereotypical presentation marked by frequent inflammatory flare-ups involving the trunk that are followed by periods of remission with residual hyperpigmentation. Herein we report a case observed in a fair-skinned French female subject. It is important that dermatologists are able to recognize it and distinguish it from other forms of pruriginous papular dermatosis, owing to the dramatic efficacy of tetracyclines in controlling the inflammatory flares and in reducing the adverse aesthetic impact of hyperpigmentation.

T-cell papulosis associated with B-cell malignancy: a distinctive clinicopathologic entity.

BACKGROUND: A distinctive eruption referred to as 'insect bite-like reaction' or 'eosinophilic dermatosis of haematological malignancy' has been described during the course of haematological B-cell malignancies (BCM). However, its clinical evolution, histopathological features and pathogenesis remain unclear. OBJECTIVES: To characterize this eruption and to investigate its pathogenesis and relationship with the underlying BCM. METHODS: In this multicenter retrospective study of the French Study Group on Cutaneous Lymphomas, 37 patients with a BCM and a cutaneous eruption consisting in chronic and/or recurrent papules, papulo-vesicles and/or nodules were included. Clinical, histopathological, immunohistochemical and molecular data were reviewed. RESULTS: No significant insect bite history or seasonal predominance was recorded. Patients had pruritic papules (81%), papulo-vesicles (43%) and nodules (38%), often predominated in the head and neck region (84%), without complete remission periods in most cases (57%). The predominant associated BCM was chronic lymphocytic leukaemia (73%). Histological and immunohistochemical review showed a dense dermal lymphocytic infiltrate predominantly composed of T lymphocytes (100%), with frequent eosinophils (77.6%); a perivascular and periadnexal (most often folliculotropic) pattern (77.6%), sometimes suggestive of a folliculotropic mycosis fungoides; clusters of tumour B cells were identified in 47% of cases using appropriate phenotyping markers. In 10/14 cases (71.4%) tested for B-cell IgH gene rearrangement, a B-cell clone was identified in skin lesions (identical to the blood clone in nine cases), whereas no T-cell clone was present. CONCLUSION: We propose the denomination 'T-cell papulosis associated with B-cell malignancy' (TCP-BCM) for this distinctive eruption. Although resulting in various histopathological pictures, it can be easily recognized by clinicians and may be identified by informed pathologists relying on some key features. An extravasation of tumour B cells with skin-homing properties associated with a secondary, predominant, T-cell immune reaction could explain the clinicopathologic aspect and the prolonged regressive and recurrent course of the disease.

[Skin pigmentation induced by meropenem and levofloxacin]. / Hyperpigmentation cutanée induite par le méropénème et la lévofloxacine.

BACKGROUND: Various cutaneous side-effects, including, exanthema, pruritus, urticaria and Lyell or Stevens-Johnson syndrome, have been reported with meropenem (carbapenem), a rarely-prescribed antibiotic. Levofloxacin (fluoroquinolone), a more frequently prescribed antibiotic, has similar cutaneous side-effects, as well as photosensitivity. We report a case of cutaneous hyperpigmentation induced by meropenem and levofloxacin. PATIENTS AND METHODS: A 67-year-old male was treated with meropenem (1g×4 daily), levofloxacin (500mg twice daily) and amikacin (500mg daily) for 2 weeks, followed by meropenem, levofloxacin and rifampicin (600mg twice daily) for 4 weeks for osteitis of the fifth metatarsal. Three weeks after initiation of antibiotic therapy, dark hyperpigmentation appeared on the lower limbs, predominantly on the anterior aspects of the legs. Histology revealed dark, perivascular and interstitial deposits throughout the dermis, which stained with both Fontana-Masson and Perls stains. Infrared microspectroscopy revealed meropenem in the dermis of involved skin. After withdrawal of the antibiotics, the pigmentation subsided slowly. DISCUSSION: Similar cases of cutaneous hyperpigmentation have been reported after use of minocycline. In these cases, histological examination also showed iron and/or melanin deposits within the dermis, but the nature of the causative pigment remains unclear. In our case, infrared spectroscopy enabled us to identify meropenem in the dermis. Two cases of cutaneous hyperpigmentation have been reported following use of levofloxacin, and the results of histological examination were similar. This is the first case of cutaneous hyperpigmentation induced by meropenem.

[An indolent and fluctuating subcutaneous mass of the skull in a 5-year-old patient: Diagnostic approach and difficulties]. / Une masse indolente et fluctuante sous-cutanée du crâne chez une patiente de 5 ans : démarche et difficultés diagnostiques.

A subcutaneous mass of the skull in children can have many different causes (infectious, tumoral, and inflammatory). We report on the case of a 5-year-old patient with a subcutaneous mass of the skull evolving over several months. The first pathological analysis concluded in Kimura disease. The progression and scarcity of this entity in children led to a second pathological analysis that showed lymphoblastic lymphoma B (LLB). This case reminds us that when there are discrepancies between pathological conclusions and clinical progression of a tumoral process, repeated analysis and immunochemistry are necessary.

[Retrospective study of hypertensive leg ulcers at Reims University Hospital: Epidemiological, clinical, disease progression data, effects of vitamin K antagonists]. / Étude rétrospective des angiodermites nécrotiques au CHU de Reims : données épidémiologiques, cliniques, évolutives et rôle des antivitamine K.

BACKGROUND: Hypertensive leg ulcers (HLU) are a form of necrotic leg ulcer. Their physiopathology is not well known and in these patients, no venous or arterial insufficiency is detected. The primary objective of this study was to evaluate the association between HLU severity and the presence or absence of concomitant vitamin K antagonist (VKA) medication. We furthermore aimed to describe the epidemiology of this entity and the prevalence of thrombophilia factors in this population. PATIENTS AND METHODS: This was a retrospective study in 54 patients hospitalized in the dermatology department of Reims University Hospital between 01/01/2007 and 31/12/2013: 23 patients were included in the "without VKA" group, and 30 were included in the "with VKA" group. Clinical and laboratory data were collected. RESULTS: The average HLU surface was higher in the "with VKA" group i.e. 35.00cm2 (min: 3.0; max: 220.0) versus 23.00cm2 (min: 5.0; max: 300.0) (P=0.05). No significant difference was found in terms of time to healing, mean hospitalization duration, HLU treatment by skin grafting, or time to recurrence after healing. Mean patient age was 74.2±9.3 years; 100% of patients had arterial hypertension, 50.9% had diabetes, and 20.8% were active smokers. Abnormal but non-significant values for thrombophilia factors were observed. CONCLUSION: Our study shows no obvious differences between patients with HLU with or without VKA medication. A prospective, comparative study is necessary to further evaluate this hypothesis, with particular emphasis on routine thrombophilia factor analysis.

[Clinical patterns and treatment of pyoderma gangrenosum in a French department]. / Caractéristiques cliniques et traitement du pyoderma gangrenosum dans la Marne.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic dermatosis for which accurate epidemiological data are limited and therapy remains a challenge. The primary study aim was to examine all cases of PG observed in our regional department over a 15-year period in order to describe the relevant characteristics and outcome under therapy. PATIENTS AND METHODS: The medical records of all patients with PG from 1997 to 2012 in the Marne department of France were studied retrospectively. Clinical and histological characteristics, comorbidities, therapeutic modalities and outcome were analysed. RESULTS: Forty-two patients were included (30 women, 12 men). A classical, ulcerative form was found in 39 cases and PG was multifocal in 28 cases. The number of lesions did not differ according to age or the presence of comorbidities. The most frequent first-line treatments were doxycycline (23 cases) and oral corticosteroids (15 cases), regardless of age, number of lesions or existence of comorbidities. Complete remission of PG was obtained in 38 cases (median time to remission: 3 months), with relapse occurring in 17 patients (median time to relapse: 12 months after treatment withdrawal). After a median follow-up of 46 months, 8 patients had died (median time to death: 26 months after treatment initiation). CONCLUSION: This is the first large French series of patients presenting PG and enabling determination of the annual incidence within the Marne department at around 4.6 cases/1000,000 inhabitants. Our study illustrates the value of first-line treatment with tetracycline, which merits confirmation by further prospective, controlled studies.