[Synergistic effect of anti-PD1 immunotherapy then radiotherapy in advanced basal cell carcinoma]. / Synergie de la séquence immunothérapie par anti-PD1 et radiothérapie au cours d'un carcinome basocellulaire avancé.

INTRODUCTION: Vismodégib is the first-line treatment for non-operable or metastatic locally advanced basal cell carcinomas (LABCC), although complete response is rare and adverse effects are common. Immune checkpoint inhibitors are currently being evaluated in this indication. Herein we report a case of LABCC that responded dramatically to sequenced "immunotherapy then radiotherapy". OBSERVATION: A 47-year-old male presented peri- and intra-orbital infiltrative LABCC that had been present for more than 10 years. After an initial response to vismodégib, further disease progression resulted in the introduction of successive lines of treatment (radiotherapy, platinum salts and itraconazole) without any significant response. Compassionate treatment with pembrolizumab was initiated. After eight courses, major clinical progression occurred with intraoral extension responsible for respiratory discomfort. Following withdrawal of pembrolizumab, high-energy radiotherapy was started with a spectacular response, both clinically and in terms of imaging. DISCUSSION: The efficacy of "radiotherapy-immunotherapy" sequencing in melanoma has been reported, due in particular to the abscopal effect and radiosensitisation. In our case, where the sequence was inverted, immunotherapy may have enhanced the effects of radiotherapy through "immunosensitisation", whereas radiotherapy alone had previously been ineffective. This observation underlines the potential value of these treatments, either combined or in sequence, and their synergistic effects and optimal association require further evaluation.

[Regression of cutaneous basal cell and squamous cell carcinoma under pembrolizumab]. / Régression de carcinomes basocellulaire et épidermoïde cutanés sous pembrolizumab.

BACKGROUND: The recommended treatments for advanced squamous cell carcinoma (SCC) (chemotherapy, radiotherapy, anti-EGFR) and advanced basal cell carcinoma (BCC) (vismodegib and sonidegib) have many side effects. Nivolumab (anti-PD1 antibody) may be used as second-line therapy in SCC of the head and neck. We report the case of a patient with advanced SCC and BCC which regressed under pembrolizumab. PATIENTS AND METHODS: A 69-year-old man consulted for a large vertex SCC measuring 15cm in diameter. He also had BCC on the left nostril and sternal Bowen disease. Radiological assessment revealed cervical and parotid lymph node involvement. Treatment with pembrolizumab 2mg/kg every 3 weeks was decided at a Multidisciplinary Concertation Meeting. Tumor regression of the vertex SCC was noted at the third course of treatment, as well as regression of the nasal BCC and the sternal Bowen disease. A complete response was observed after 11 courses of treatment for SCC, 7 courses for BCC, and 10 courses for Bowen disease. CONCLUSION: We report an original case of cure of BCC with anti-PD1 (pembrolizumab) prescribed for locally advanced inoperable SCC. The place of this treatment in the therapeutic arsenal remains to be defined. Clinical trials are in progress concerning use of this treatment in advanced cutaneous SCC and inoperable BCC.

[An original reconstruction technique for double upper white lip defect]. / Une technique originale de réparation d'une double perte de substance de l'hémilèvre supérieure blanche.

INTRODUCTION: Herein we report a case of a surgical repair of double substance loss along the nasolabial groove by means of a double superior advancement flap from the cheek to the upper lip that we have here called the "double jigsaw puzzle" flap. OBSERVATION: A 58-year-old man underwent surgery for 2 basal cell carcinomas located in the right white upper lip. The two lesions were first removed and the two defects were then carried over to the cheek symmetrically along the nasolabial groove. Two triangular "lugs" were excised on both sides to allow horizontal advancement of the cheek to the upper lip to fill the 2 gaps from the upper lip excisions like 2 pieces of a puzzle. The nasolabial groove was then recreated by deep anchoring stitches, with suturing comprising superficial stitches. DISCUSSION: This surgical flap can be created quickly and easily and yields good aesthetic results in the immediate postoperative period and in the longer term, and the scar is totally masked within the nasolabial fold. The only limitation to a good aesthetic outcome is the presence of a small area of hairless skin within what constitutes an area of hair growth in male subjects.

[Histopathological study of basaloid follicular hamartoma]. / Hamartome folliculaire basaloïde : étude anatomoclinique.

INTRODUCTION: Basaloid follicular hamartoma (BFH) is a rare tumor first described in 1985. It bears clinical and histologic similarities with basal cell carcinoma (BCC), in particular the so-called infundibulocystic form. We performed a single-center clinicopathological study of a series of typical cases of this entity that is occasionally difficult to diagnose. MATERIALS AND METHODS: All cases of BFH seen at the Dermatopathology Laboratory of Strasbourg University Hospital were included and analyzed by means of HE staining and Ber-EP4 and PHLDA1 immunolabelling. Diagnosis was made in the event of basaloid proliferation with anastomosing cords developed from a hair follicle. Clinical data were collected from clinical files. RESULTS: We identified 15 cases in 13 patients of mean age 44.8 years (range: 4 to 90) and the sex-ratio was 5/8. Lesions consisted of flesh-colored papules measuring 0.3 to 1.2cm in diameter, without any preferential site. Three patients had multiple lesions consisting of several coalescent papules on a breast for one, sparse papules on the back for another, and hundreds of linear unilateral BFHs, associated with osseous abnormalities, characteristic of Happle-Tinschert syndrome, for the third. All tumors were limited to the superficial and mid dermis, with a vertical orientation and connection to the epidermis in 14 of the 15 patients. In some cases, the outermost cells were basophilic while the central cells were eosinophilic. Peripheral palisading and clefting were frequently observed. Keratin cysts or sebaceous ducts were consistently present, indicating follicular differentiation. Ber-EP4+ cells were restricted to the periphery of the cords and PHLDA1 was weakly expressed. DISCUSSION: BFH is a rare entity that must be differentiated from BCC. It presents as solitary or multiple lesions, either grouped in plaques or with a generalized or linear unilateral distribution. Generalized BFH may be associated with autoimmune diseases and linear unilateral BFH with osseous, dental and cerebral abnormalities in Happle-Tinschert syndrome. It is important to distinguish BFH from BCC to avoid inappropriate aggressive treatment.

[Use of the autologous dorsal dermis in reconstruction of the posterior palpebral lamella in blepharopoiesis]. / Utilisation du derme dorsal autologue en reconstruction lamellaire palpébrale postérieure en blépharopoïèse.

OBJECTIVES: Blepharopoiesis represents a double aesthetic and functional challenge. If anterior lamellar reconstruction is less discussed, the variety of posterior lamellar substitutes testifies that none is ideal. We report here our experience of the use of autologous dermal dermis as posterior lamellar substitutes in bilamellar blepharopoiesis. PATIENTS AND METHOD: We performed a single-center retrospective observational study of seven patients undergoing blepharopoiesis using dorsal dermal autograft as posterior lamellar substitute. RESULTS: Between September 2011 and January 2017, seven patients aged of 80.9 years on average were cared for. The defect, affecting in 6 cases on 7 the lower eyelid, concerned almost three-quarter of the length of the eyelid. These defects followed the excision of basal cell carcinomas. Procedures performed under local anesthesia have simple follow-up without complications of the donor site. The superficial surface of the graft in contact with eyeball was covered in 2.4 months with a non-keratinized squamous epithelium like the conjunctiva. Two patients presented ocular functional signs during 2 months without keratitis. Two patients required a second correction procedure. CONCLUSION: The use of the dorsal dermis seems reliable, simple, fast, possible under local anesthesia and sedation, achievable in one operative time, outpatient, without temporary tarsorraphy. The graft is available in large quantities and its removal is not morbid. The good functional and esthetic results suggest that the autologous dermal dermis could represent the main alternative to palatal fibromucosa as a posterior lamellar substitute in old population.

[Microcystic adnexal carcinoma: A case report]. / Carcinome annexiel microkystique : à propos d'une observation.

We report a case of microcystic adnexal carcinoma in a 80-year-old woman. This is a rare malignant adnexal cutaneous tumor with glandular and follicular differentiation, rare, often asymptomatic, with late diagnosis and slow growth, locally aggressive and rarely metastatic. The distinction with other benign and malignant skin tumors is difficult.

Place de la radiothérapie dans le traitement du carcinome basocellulaire: Radiation therapy for basal cell carcinoma.

Radiotherapy is an available but not well-known treatment for management of basal cell carcinoma. National organizations have established that standard therapy is complete surgical removal and radiation therapy is an option for inoperable tumors or those where the post-operative defect would be cosmetically disfiguring or functionally disabling. These therapeutic options, with histological sample, should be considered in the multidisciplinary management of patients with basal cell carcinoma. There are several types of radiotherapy: external radiation or interstitial brachytherapy, unfortunately, there is no consensus in the literature and the range of radiation regimens in common use is large. Very few randomized studies have been conducted to defi the optimum treatment in terms of recurrence rate, cosmetic outcome and side-eff In most of studies, the overall local control rate was between 80-100% and over 90% of patients reported good or excellent cosmetic outcome. Side-eff of radiotherapy most commonly reported are minor but in young patients one must be alert to the theoretical possibility of the induction of secondary malignancies. Cet article fait partie du numéro supplément Prise en charge des carcinomes basocellulaires difficiles à traiter réalisé avec le soutien institutionnel de Sun Pharma.

[Cytopenia under topical imiquimod in two patients treated with oral hydroxyurea]. / Cytopénies sous imiquimod topique chez deux patients traités par hydroxyurée.

BACKGROUND: Aldara® is a topical immunomodulatory treatment. The risks of systemic passage are minimal. There have been rare reports of systemic adverse effects. PATIENTS AND METHODS: Case 1. Five sachets weekly of imiquimod were prescribed for Bowen's disease on the forearm in a patient known to have essential thrombocytosis under Hydrea®. His CBC was normal (6000 leukocytes/mm3, 2200 PMN/mm, 230,000 platelets/mm3). Imiquimod was given in 15 sachets weekly. Fifteen day later, the patient presented bicytopenia (3000 leukocytes/mm3, 1400 PMN/mm3, 119,000 platelets/mm3). Hydroxyurea and imiquimod were suspended until normalization of CBC. Hydroxyurea was resumed without recurrence of the bicytopenia. The patient's history included an identical episode following application of imiquimod. Case 2. Five sachets weekly of imiquimod were prescribed for actinic keratosis on the scalp in a patient known to have primary polycythemia under hydroxyurea. Her CBC was normal except for anemia (Hb 11.5g/L, 160,000 platelets/mm3, 1100 lymphocytes/mm3). Imiquimod was given in 12 sachets weekly. Ten days later, anemia increased (Hb 10g/dL) with lymphopenia (800/mm3) and thrombocytopenia (115,000/mm3). Suspension of imiquimod resulted in normalization of the previous CBC values. DISCUSSION: . The literature review identified reports of dose-dependent lymphopenia under oral imiquimod but not under Aldara®. The National Pharmacovigilance Database listed 10 cases of hematological disorders most likely caused by Aldara®. Hydroxyurea may induce cytopenia, and while it was not considered the sole causative agent in this case, it is likely to have had a triggering role in these patients with blood dyscrasias. Our findings show that misuse of imiquimod carries a potential risk of hematologic abnormality in patients receiving concomitant hydroxyurea, a commonly combined drug.

[Complications with surgical treatment of basal cell carcinomas in individuals over 75 years of age: A retrospective study of prognostic factors in 158 cases]. / Complications du traitement chirurgical des carcinomes basocellulaires après 75 ans. Étude rétrospective des facteurs pronostiques sur 158 cas.

INTRODUCTION: Basal cell carcinoma (BCC) is a pathology that evolves locally and it is common in elderly subjects whose frailty could restrict the indications for the reference treatment, which is based on surgery. The aim of this study was to investigate the morbidity and the mortality associated with surgical treatment of BCC in patients over 75 years of age, so as to identify possible prognostic factors for postoperative complications. MATERIALS AND METHODS: This was a retrospective study carried out with patients over 75 years of age who were treated surgically for one or several BCC between 2010 and 2015 in the reconstructive and cosmetic plastic surgery unit of the Saint-Louis Hospital in Paris (France). We collated the demographic characteristics, the characteristics of the treatment, as well as the rate of major postoperative complications. We performed a univariate and then a multivariate analysis of the various risk factors that were identified. RESULTS: A total of 158 patients were analyzed and they exhibited a rate of major complications of 12%. The statistical analysis identified five significant risk factors: being over 85 years of age (P=0.006), long-term use of anticoagulant treatment (P=0.02), the presence of at least one comorbidity (P=0.018), a conventional hospitalization (P=0.002), and the use of general anesthesia (P=1.2e-10). CONCLUSION: Five risk factors for major postoperative complications with the surgical treatment of BCC in patients over 75 years of age were identified. These factors may provide direction to medico-surgical teams in regard to the optimal treatment of BCC in elderly patients.

Full-thickness skin grafts for lower leg defects coverage: Interest of postoperative immobilization.

INTRODUCTION: Full-thickness skin graft is an effective reconstruction method after excision of skin lesions on the lower limb that are not amenable to primary closure. The randomness of graft take is the major drawback of this procedure. OBJECTIVE: The objective of the study was to evaluate the outcome of full-thickness skin grafts (FTSG), used to repair lower leg defects after excision of skin lesions, after a 5-day immobilization period. MATERIAL AND METHODS: All consecutive patients who underwent FTSG to cover defects below the knee between November 2011 and January 2016 were retrospective reviewed. Graft take was assessed and defined as good (>90% graft take), moderate (between 50% and 90% graft take), or poor (<50% graft take). RESULTS: Seventy patients were included. Median age was 70 years (range, 18-92 years). The median area of the defect was 12cm2. Graft take was good in 64 patients (91.4%), moderate in 3 patients (4.3%), and poor in 3 patients (4.3%) at Day 5. Complications included hematoma (11%), infection (14%) and venous thrombosis (3%). CONCLUSION: Full-thickness skin graft is a reliable method to repair defects on the lower leg after removal of skin lesions. A 5-day immobilization period can improve the graft take. The authors have indicated no significant interest with commercial supporters.

[Eruptive epidermoid cysts during topical imiquimod treatment]. / Éruption de kystes épidermiques après application d'imiquimod topique.

BACKGROUND: Imiquimod is a local immune-response modifier that works by stimulating innate and acquired immunity. It is frequently used to treat superficial basal cell carcinoma, the most common form of skin cancer. Marked local inflammatory reaction is common during treatment. We report a case of the rare condition, multiple eruptive milia, during topical imiquimod therapy. PATIENTS AND METHODS: A 67-year-old male patient presented infiltrating basal cell carcinoma above the left eyebrow. The patient underwent surgery and skin grafting. He presented superficial relapse at the periphery of the graft and was initially treated with Aldara®. Fifteen days after initiation, Aldara® was withdrawn due to a critical inflammatory reaction. A few weeks after complete healing, an erythematous annular plaque of milia, excluding the graft zone, appeared. This element was confirmed by histopathology. DISCUSSION: The most common local side effects reported with Aldara® are erythema, irritation and crusting. Reports of eruptive milia following Aldara® therapy are rare and they are never mentioned in the summary of product characteristics. Application of imiquimod in fact induces local inflammatory reaction due to stimulation of local cytokines, which can result in marked reaction in the infundibular epithelium of hair follicles and thus in the production of abnormal keratin that can cause pilosebaceous duct obstruction and thus the formation of epidermoid cysts. This pathological mechanism explains the absence of lesions on the skin graft of the inner arm. CONCLUSION: The occurrence of eruptive milia during treatment with Aldara® is rarely described. The timing of occurrence of these eruptive milia as well as the mechanism of action of the drug made such a reaction highly probable in our patient.

[Why is it important to differentiate trichoblastic carcinomas (CT) from basal cell carcinomas (CBC). About 21 cases]. / De l'intérêt de différencier les carcinomes trichoblastiques (CT) des carcinomes basocellulaires (CBC). À propos de 21 cas.

Trichoblastic carcinoma is a rare epithelial malignant epithelial tumor, its diagnosis is difficult and the therapeutic management is non-consensual. This retrospective study, carried out between 2009 and 2015, covered 21 cases and analyzed the diagnostic and therapeutic characteristics of trichoblastic carcinomas. Sex ratio is 2. Trichoblastic carcinoma predominated in the face (65% of cases), particularly in perinasal (30% of cases). Its clinical presentation is in 95% of cases as basal cell carcinoma, which is the first clinical diagnosis evoked. The average size of the tumors was 2.3cm in diameter (from 0.7cm to 15cm). The treatment of these tumors is surgical: the margins retained were on average 0.7cm (0.5cm to 1cm). The first excision was mostly performed under local anesthesia, healthy borders were found in less than 40% of cases, requiring another intervention under general anesthesia with reconstruction by flap or skin graft in nearly 80% of cases. The lymph node metastasis rate was 5%. Three cases of recurrence (17%) occurred between 18 months and 6 years follow-up, despite complete resection. One case recurred three times. These results highlight the difficulty of diagnosing trichoblastic carcinomas, often confused with basal cell carcinomas. Though larger, poorly limited and infiltrating, trichoblastic carcinomas are not really distinguished from basal cell carcinomas. Only the anatomopathological examination of the excision piece make it possible to conclude, the biopsy being most often insufficient. Their local aggressiveness requires a greater margin of excision. The micrographic analysis of Mohs, for the periorificial lesions of the face, would reduce margins, increase their reliability and limit the number of surgical revisions. Finally, the literature reports a high rate of ganglion and visceral metastases (between 9.5 and 11%). Initial search for distal lymph node or metastatic involvement is essential, as well as regular clinical follow-up.

[Basal cell carcinoma with matrical differentiation]. / Carcinome basocellulaire à différenciation matricielle.

Basal cell carcinoma with matrical differentiation is a very rare variant of basal cell carcinoma. To our knowledge, less than 30 cases have been reported. This tumor is composed of basaloid lobules showing a differentiation toward the pilar matrix cells. Recently, it has been demonstrated that beta-catenin would interfer with physiopathogenesis of matrical tumors, in particular pilomatricomas, but also basal cell carcinomas with matrical differentiation. This is a new case, with immunohistochemical and molecular analysis of beta-catenin, in order to explain its histogenesis.

[High-resolution ultrasonography for differential diagnosis between nodular basal carcinoma and sebaceous hyperplasia of the face: A pilot study]. / Échographie cutanée haute résolution dans le diagnostic différentiel entre carcinome basocellulaire nodulaire et hyperplasie sébacée du visage: une étude pilote.

BACKGROUND: Clinical differential diagnosis between incipient nodular basal carcinoma (NBC) and sebaceous hyperplasia (SH) of the face is difficult in some cases. A comparative histological analysis of these two entities led us to the hypothesis that 20MHz high-resolution ultrasonography (HRUS) may enable differentiation between NBC and SH. PATIENTS AND METHODS: Seventy-seven facial tumours requiring histological confirmation to distinguish between NBC and SH were scanned using HRUS before excision. No other imaging technique was used. The ultrasound scans were submitted to two blinded reviewers who were asked to classify the ultrasound pictures of the tumours as either hypoechoic or isoechoic/hyperechoic. Hypoechogenicity was defined as a diagnostic criterion for NBC. RESULTS: Reviewer response reproducibility for 2 images of the same tumour was 90%. Both reviewers agreed regarding the echogenicity classification of an image in 87.4% of cases. The sensitivity of the procedure was 90.9% for detection of NBC and 89.4% for detection of malignant lesions. Specificity was 69.6% for detection of basal cell carcinomas and 78.8% for detection of malignant lesions. DISCUSSION: HRUS is a non-invasive examination technique with excellent sensitivity for the detection of NBC in differential diagnosis with SH. Hypoechogenicity is not specific to NBC. The sensitivity of HRUS in our study suffered as a result of ultrasonography difficulties regarding unexpected differential diagnoses of NBC as well as tumour localisation in seborrhoeic areas.

[What's new in oncodermatology in 2015?]. / Quoi de neuf en oncodermatologie en 2015?

Oncodermatology is the topic of constant innovation since 5 years. These innovations have drammatically modified the prognostic of skin cancers and induced a change in the paradigm that drives the whole oncology. Once again in 2015, melanoma is the key topic of scientific communication, with promising results. However, unmet clinical needs must be kept in light. Some diseases, such as squamous cell carcinoma or cutaneous lymphoma remain poorly evaluated. This article was designed as a review of litterature. All keywords of oncodermatology were searched in the main journals of dermatology, oncology and internal medicine. Despite methodologic restrictions, the number of articles imposed a choice based on opinion. The final goal was to transmit author's enthousiasm and the most important results.

[PDT panoramic view. Principle, photosensitizers, light sources and validated indications in dermatology]. / Revue Panoramique de la PDT. Principe, photo-sensibilisateurs, sources de lumières et indications validées en dermatologie.

INTRODUCTION: Photodynamic therapy (PDT) combines the use of a topical sensitizer and its excitation with a light of appropriate wavelength. Its use in dermatooncology has been possible in France in 2006 when the methyl ester ALA or Metvixia® got approved. OBJECTIVE: To provide a panoramic view of validated indications of PDT in oncodermatology. METHOD: This work is based on the review of the literature as well as available guidelines or recommendation on PDT in dermatology. RESULTS: Standardized protocols and results of the main clinical trials are given for the three major indications in dermatology: actinic keratosis, basal cell carcinoma and Bowen disease. CONCLUSION: PDT has its role to play in the treatment of multiple superficial carcinomas and cutaneous precancerous lesions and its main advantage resides in its optimal healing.

[Recurrence of palpebral basal cell carcinoma according to histological margins]. / Récidive des carcinomes basocellulaires palpébraux selon les marges histologiques.

BACKGROUND: Basal cell carcinomas (BCCs) represent 90% of malignant tumors of the eyelids, which can be locally invasive and destructive. The observation of histological safety margins (MHS) allows for the prevention of recurrence while maintaining a fair compromise between aesthetics and functionality. However, to date, there is no consensus or national recommendations concerning the MHS to be observed according to the various histological subtypes of BCCs. METHODS: Through a retrospective analysis of patient records and corresponding excisional slides, we studied the 6-year recurrence rate of 98 patients who underwent surgery for palpebral BCC. RESULTS: MHS were mostly absent in the excisional specimens of recurrent BCCs and significantly more narrow than in non-recurrent BCCs, on average over 2mm. CONCLUSION: The results of our study suggest that an average MHS greater than 2mm prevents most recurrences.

Management of eyelids' primary malignancies.

Purpose: We report our experience in surgical management of primary malignant tumors of the eyelids. We have specified the various surgical techniques used, as well as functional and anatomical results.Patients and methods: A review of patients admitted for malignant tumor of the eyelids in the oculoplastic department of the Hedi Raies Institute of Ophthalmology from January 2012 to December 2021.Results: One hundred and twenty-three patients with malignant eyelid tumors were hospitalized. Surgical treatment involved 114 tumor lesions, which represents 95% of the cases. One hundred and eleven lesions (97.4%) had been operated by simple tumor resection. Safety margins were, respectively, 4 mm in 63.2% and from 5 to 6 mm in 34.2%. Extemporaneous histological examination was performed in three cases (2.6%). Reconstruction involved the anterior lamella (AL) in 92 cases (80.7%), the posterior lamella (PL) in 66 cases (57.9%), the medial canthus in 18 cases (15, 8%), and lateral canthus in 4 cases (3.5%). The excision was oncological in 85 cases (74.6%) and incomplete in 19 cases (16.7%). Tumor recurrence occurred in seven cases (6.1%), after an average delay of 36 months.Conclusion: The anatomical and functional features of the eyelids require a good reconstruction of the transfixion eyelid defect. Many reconstruction methods are available, allowing extensive and complex palpebral repairs. Oncologic prognosis is conditioned by the surgical quality.