Vicente García-Patos

Cutaneous infections due to nontuberculous mycobacteria: histopathological review of 28 cases. Comparative study between lesions observed in immunosuppressed patients and normal hosts

To evaluate the histopathological features observed in patients with cutaneous infections due to nontuberculous mycobacteria (NTM) and to compare the histopathological patterns observed in immunosuppressed patients and normal hosts. Twenty‐eight biopsy specimens corresponding to 27 patients with cutaneous infections due to NTM were reviewed. Eighteen biopsies corresponded to normal hosts (14 Mycobacterium marinum, 2 Mycobacterium chelonae, 1 Mycobacterium terrae and 1 Mycobacterium gordonae) and 10 biopsy specimens were obtained from 9 immunosuppressed patients (3 Mycobacterium chelonae, one of which had two biopsies, 1 Mycobacterium abscessus, 2 Mycobacterium kansasii, 1 Mycobacterium marinum, 1 Mycobacterium avium complex and 1 Mycobacterium simiae). A panel of histopathological features was evaluated by two independent observers in each biopsy specimen. Epidermal changes (acanthosis, pseudoepitheliomatous hyperplasia, exocytosis) were mainly observed in M. marinum infections. In immunosuppressed patients the infiltrate tended to be deeper, involving the subcutaneous tissue (100%) with a more diffuse distribution and constant abscess formation. A marked granulomatous inflammatory reaction was observed in 83% of immunocompetent and in 60% of immunosuppressed patients. In immunosuppressed patients a relationship between the chronic evolution of the disease and granuloma formation was demonstrated. A diffuse infiltrate of histiocytes with occasionally foamy appearance was noted in three biopsy specimens from three patients with AIDS. Acute and chronic panniculitis was detected in 8 biopsy specimens. In one biopsy (M. chelonae) an acute suppurative folliculitis was observed. Different histopathological patterns can be noted in biopsy specimens from cutaneous nontuberculous mycobacterial infections. The evolution of the disease and the immunologic status of the host may explain this spectrum of morphological changes. Tuberculoid, palisading and sarcoid‐like granulomas, a diffuse infiltrate of histiocytic foamy cells, acute and chronic panniculitis, non‐specific chronic inflammation, cutaneous abscesses, suppurative granulomas and necrotizing folliculitis can be detected. Suppurative granulomas are the most characteristic feature in skin biopsy specimens from cutaneous NTM infections. Some histopathological patterns seem more prevalent in immunosuppressed patients.

Clinical patterns of cutaneous nontuberculous mycobacterial infections.

Background  Cutaneous nontuberculous mycobacterial infections result from external inoculation, spread of a deeper infection, or haematogenous spread of a disseminated infection. There are two species‐specific infections (fish‐tank or swimming‐pool granuloma, due to Mycobacterium marinum, and Buruli ulcer, caused by M. ulcerans). Most infections, however, produce a nonspecific clinical picture.

A review of causes of Stevens–Johnson syndrome and toxic epidermal necrolysis in children

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening conditions almost exclusively attributed to drugs. The incidence in children is lower than in adults and has a better outcome. Mycosplama pneumoniae infection may be involved in some cases of paediatric SJS. The main etiologic factors for both SSJ and TEN are sulphonamides and anticonvulsants, followed by penicillins and non-steroidal anti-inflammatory drugs. In rare instances, paracetamol is the only suspected drug. By contrast with adults, allopurinol, oxicams and nevirapine are not identified as causative agents in children, probably due to differences in drug prescriptions. The only aspects of treatment that have been proved to improve survival are the rapid withdrawal of the suspected offending drugs and an optimal supportive therapy with emphasis in nutritional support, accompanied by management of denuded skin areas. The use of specific therapies remains controversial.

Identification and genotyping of human papillomavirus in a Spanish cohort of penile squamous cell carcinomas: Correlation with pathologic subtypes, p16INK4a expression, and prognosis

BACKGROUND Penile squamous cell carcinoma (PSCC) is a tumor with a high metastatic potential. In PSCC the attributable fraction to human papillomavirus (HPV) is not well established. OBJECTIVE We sought to provide novel data about the prevalence of HPV in a large series of penile intraepithelial neoplasia (PeIN) and invasive PSCC, correlating the results with the histologic subtype, p16(INK4a) immunostaining, and prognosis. METHODS A total of 82 PSCC were included in the study, 69 invasive and 13 PeIN. HPV detection was performed by polymerase chain reaction with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe assay. P16(INK4a) immunohistochemical expression on tissue microarrays was also analyzed. RESULTS HPV DNA was identified in 31 of 77 (40.2%) PSCC (22 of 67 invasive and 9 of 10 PeIN). In 25 of 31 (80.6%) cases HPV-16 was identified. HPV detection was significantly associated with some histologic subtypes: most basaloid and warty tumors were high-risk HPV (hrHPV) positive, whereas only 15% of usual PSCC were hr-HPV positive. All hrHPV-positive PSCC had an adjacent undifferentiated PeIN. Strong p16(INK4a) immunostaining correlated with hrHPV infection. Most undifferentiated PeIN showed p16(INK4a) immunohistochemical overexpression. Both hrHPV-positive and p16(INK4a)-positive tumors showed a better overall survival without reaching statistical significance. LIMITATIONS This was a retrospective study. CONCLUSIONS Our results suggest that most hrHPV-positive PSCC develop from undifferentiated hrHPV-positive PeIN. P16(INK4a) immunostaining may be useful in identifying both etiologically related hrHPV-positive tumors and those with better outcome. The routine use of p16(INK4a) staining should be incorporated in histologic evaluation of PSCC.

Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a review of the experience with paediatric patients in a university hospital.

Background  Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life‐threatening drug reactions considered to be part of the spectrum of a single pathological process.

Folliculocystic and collagen hamartoma of tuberous sclerosis complex

BACKGROUND Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by tumors and hamartomas in several organs including the skin. OBJECTIVE We sought to describe a new type of complex hamartoma in patients with TSC. METHODS This was a retrospective clinical and histopathologic evaluation of 6 cases. RESULTS The skin lesions consisted of large, painless, infiltrated plaques that were first noticed at birth or during early infancy on the abdomen, thigh, back, or scalp. In time, the plaques became studded with numerous follicular comedo-like openings and cysts containing and draining a keratinous or purulent material. The main histopathologic features were: abundant collagen deposition in the dermis and extending into the underlying fat; concentric, perifollicular fibrosis surrounding hair follicles; and comedones and keratin-containing cysts lined by infundibular epithelium, some of which were ruptured with secondary granulomatous reaction. Five of the 6 patients had a clinical diagnosis of TSC. LIMITATIONS Genetic testing was performed in only one patient. CONCLUSION This distinctive folliculocystic and collagen hamartoma has not been recognized previously in association with TSC.

Use of biological treatments in patients with hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic skin disease which causes a great impact in the quality of life. Multiple therapeutic options have been proposed, and recently the potential use of biological drugs in severe cases has been postulated.

mTOR Signaling Pathway in Penile Squamous Cell Carcinoma: pmTOR and peIF4E Over Expression Correlate with Aggressive Tumor Behavior

PURPOSE Penile squamous cell carcinoma is a rare neoplasm associated with a high risk of metastasis and morbidity. There are limited data on the role of the mTOR signaling pathway in penile squamous cell carcinoma carcinogenesis and tumor maintenance. We assessed a possible role for mTOR signaling pathway activation as a potential predictive biomarker of outcome and a therapeutic target for penile cancer. MATERIAL AND METHODS A cohort of 67 patients diagnosed with invasive penile squamous cell carcinoma from 1987 to 2010 who had known HPV status were selected for study. Tissue microarrays were constructed with 67 primary penile squamous cell carcinomas, matched normal tissues and 8 lymph node metastases. Immunohistochemical staining was performed for p53, pmTOR, pERK, p4E-BP1, eIF4E and peIF4E. Expression was evaluated using a semiquantitative H-score on a scale of 0 to 300. RESULTS Expression of pmTOR, p4E-BP1, eIF4E and peIF4E was increased in penile tumors compared with matched adjacent normal tissues, indicating activation of the mTOR signaling pathway in penile tumorigenesis. Over expression of pmTOR, peIF4E and p53 was significantly associated with lymph node disease. peIF4E and p53 also correlated with a poor outcome, including recurrence, metastasis or disease specific death. In contrast, pERK and p4E-BP1 were associated with lower pT stages. pmTOR and intense p53 expression was associated with HPV negative tumors. CONCLUSIONS Activation of mTOR signaling may contribute to penile squamous cell carcinoma progression and aggressive behavior. Targeting mTOR or its downstream signaling targets, such as peIF4E, may be a valid therapeutic strategy.

Generalized acquired cutis laxa associated with coeliac disease: evidence of immunoglobulin A deposits on the dermal elastic fibres

Summary Acquired cutis laxa (ACL) is an uncommon elastolytic disorder of unknown aetiology. In rare instances. ACL has been reported in association with autoimmune diseases and dermal deposit of immunoglobulins, suggesting that destruction of elastic tissue may be immunologically mediated. We report a 35‐year‐old man with generalized acquired cutis laxa (GACL) associated with a persistent papular erythematous eruption that histopathologically showed some resemblance to dermatitis herpetiformis. A marked reduction and degeneration of dermal elastic fibres was noted in biopsies from loose‐hanging skin. Direct immunofluorescence from non‐inflammatory loose skin revealed granular immunoglobulin A (IgA) deposits at the basement membrane zone and fibrillar IgA deposits in the dermal papillae. IgA deposits were also observed on the elastic fibres of the reticular dermis. Electron microscopy of skin from the submammary fold revealed fragmented elastic fibres, partial absence of peripheral microfibrils and abundant neutrophils, some of which were degranulated and adjacent to elastic fibres. Immunoelectron microscopy of an erythematous papule revealed IgA deposits around dermal elastic fibres. Antigliadin, antireticulin and antiendomysium antibodies were present. Jejunal biopsies showed a gluten‐sensitive enteropathy. A possible IgA‐mediated immune mechanism for the development of GACL in our patient is suggested.

Ofuji Papuloerythroderma in a Patient with the Acquired Immunodeficiency Syndrome

Ofuji papuloerythroderma (OPE) is a distinctive clinical entity of unknown etiology which occasionally may be associated with B-cell and T-cell lymphomas and visceral malignancy. We describe a case of OPE in a male with the acquired immunodeficiency syndrome. To our knowledge, this is the first report of OPE in a patient infected by the human immunodeficiency virus.