Implication of wide surgical excision in minimizing positive margins and consequential secondary excision - a retrospective comparative study involving 106 basal cell carcinoma cases.

OBJECTIVE: The use of current surgical techniques in the management of skin cancers that are not amenable to other treatment options has become the cornerstone of dermatological surgical intervention. Among the many benign lesions and malignant lesions, such as squamous cell carcinomas, melanomas, and Merkel cell carcinomas, the tumors that are commonly excised surgically are the basal cell carcinomas (BCC). Although the majority of BCC lesions spread locally and are rarely metastatic, these lesions may recur, especially, if the excised tissue consists of positive surgical margins. As BCC lesions are more common on the head, face, and neck regions, inadvertent positive margin excisions to help avoid major disfigurement of the regions may contribute to their recurrence. Trichoepithelioma (TE) is a benign tumor that bears a close resemblance to BCC, and therefore, clinicians encounter difficulty in differentiating between TE and BCC lesions. Clinicians have to rely on histopathology and immune-histochemical markers to rule out TE. This differentiation is crucial to make a definitive diagnosis of BCC and subsequently, employ a more aggressive surgical excision approach to treat this invasive tumor as compared with TE. Our focus in this article is to highlight only the surgical excision management of local and or locally invasive BCCs and report the success rate of our hospital's Dermato-venereology clinic (DVC) in Timisoara, Romania. This article highlights the role of an appropriate wide local lesion excision (5 mm) with negative surgical margins in the prevention of further surgical interventions, be it for corrective or esthetic reasons. PATIENTS AND METHODS: This is a retrospective study that summarizes the evaluation of 120 lesions from 106 patients who were treated for BCCs at DVC (University Hospital), using a wide surgical excision method.  Following the Romanian Society of Dermatologists guidelines, local non-aggressive BCC lesions were excised with margins of 5 mm and up to 1 cm for the aggressive sclerosing subtype. RESULTS: The results of the audit of a sample of 120 lesions from 106 patients demonstrated that none of the surgically treated patients had recurrences and only 23 (19.16%) had positive surgical margin lesions. Out of these, 17 (73.91%) lesions underwent second surgical excision, while only three (13.04%) showed the presence of a residual tumor. The evaluation results may encourage dermatologists worldwide to make appropriately sized excision, especially in regions other than the head and neck, to avoid positive surgical margins and eliminate the need for consequent surgery. CONCLUSIONS: For a better post-surgical prognosis of BCC, the authors recommend the practice of a wide margin excision (5 mm) during the primary surgery to avoid secondary surgery, especially if the tissue in the region is not sparse and chances of causing major disfigurement are minimal. As our findings suggest, only a few cases have the presence of residual tumor in the second surgery, hence authors also advocate the necessity to inform the patients about the merits of a second surgery, clearly mentioning the possibility of the absence of tumor even in the presence of positive margin.

DNA copy number imbalances in primary cutaneous lymphomas.

BACKGROUND: Cutaneous lymphomas (CL) represent a clinically defined group of extranodal non-Hodgkin lymphomas harbouring heterogeneous and incompletely delineated molecular aberrations. Over the past decades, molecular studies have identified several chromosomal aberrations, but the interpretation of individual genomic studies can be challenging. OBJECTIVE: With a comprehensive meta-analysis, we aim to delineate genomic alterations for different types of CL and propose a more accurate classification in line with their various pathogenicity. METHODS: We searched PubMed and ISI Web of Knowledge for publications from 1996 to 2016 reporting the investigation of CL for genome-wide copy number alterations, by means of comparative genomic hybridization techniques and whole-genome sequencing and whole-exome sequencing. We then extracted and remapped the available copy number variation (CNV) data from these publications with the same pipeline and performed clustering and visualisation to aggregate samples of similar CNV profiles. RESULTS: For 449 samples from 22 publications, CNV data were accessible for sample based meta-analysis. Our findings illustrate structural and numerical chromosomal imbalance patterns. Most frequent CNAs were linked to oncogenes or tumour suppressor genes with important roles in the course of the disease. CONCLUSION: Summary profiles for genomic imbalances, generated from case-specific data, identified complex genomic imbalances, which could discriminate between different subtypes of CL and promise a more accurate classification. The collected data presented in this study are publicly available through the 'Progenetix' online repository.

Non-keratinizing undifferentiated carcinoma of the nasopharynx.

Nasopharyngeal carcinoma is the predominant tumor type arising in the nasopharynx with cervical lymph nodes present in 60-90% of all cases at the time of presentation. The most frequent pathological varieties include squamous cell carcinoma well-differentiated keratinizing, moderately differentiated non-keratinizing and an undifferentiated type. We present a case of non-keratinizing undifferentiated carcinoma of the nasopharynx with parapharyngeal and middle cranial fossa space involvement in an 18-year-old male who has been admitted in our hospital for recurrent right ear otitis media. Symptoms consisted in mild conductive hearing loss, trigeminal V2 nerve anesthesia, right ear tinnitus, mild dysphagia, mild dysphonia, right hypoglossal nerve paralysis and right Claude Bernard-Horner's syndrome. Clinical examination revealed no lymph node masses, chest X-ray corresponding to a normal thoracic image. Cranial contrast enhanced CT scan showed a non-homogenous mass of 5.4/4.5/5.5 cm from the level of the right rhinopharyngeal wall, extending in the right parapharyngeal space, invading the right middle cranial fossa. Cranial MRI with contrast enhancement revealed a rhino- and parapharyngeal mass of 5.5/4.6/5.3 cm with intracerebral extension in the right cavernous sinus, right internal carotid artery being engulfed by the tumor mass with partial compression. Several lymph node masses of 1.7/1.2 cm were also revealed. We performed rhinopharyngeal biopsy, right tympanotomy and grommet tube insertion. The tissue specimens were processed with routine histological technique. Subsequent immunohistochemical reactions for pan-cytokeratin AE1/AE3 and leukocytes common antigen were performed. The histological examination of routine stained slides showed that malignant tumor cells had a syncytial pattern of growth in a background of small lymphocytes. The positivity of tumor cells for pan-cytokeratin established the final diagnosis of non-keratinizing undifferentiated carcinoma. The age of onset, the clinical signs and symptoms and minimum involvement of lymph nodes represents the particular aspects of the case.

Unusual variant of blue nevus associated with dermatofibromas.

The blue nevus is a variant of a melanocytic nevus that presents as blue-gray to blue or black papules or nodules measuring up to 1 cm in diameter; it has a predilection for females and can be congenital or acquired. The classification of blue nevi is complex, with biological behavior being benign, borderline, or malignant. The case we present is one of a 40-year-old woman with multiple dermatofibromas that appeared and increased gradually in size during pregnancy. Physical examination revealed three spherical, brownish to red-purple nodules localized on the left leg, right shoulder and right laterocervical area. In addition, on her right forearm, there was a 0.3 cm nodule with a discreet non-pigmented, elevated area and a blue perilesional border that appeared in her childhood, affirmative after stinging herself with a pencil. The patient's family history was negative for significant lesions. The laboratory and imagistic findings were normal. Four skin biopsies were performed. The histopathological examination revealed an uncommon blue nevus with two different populations of pigmented cells: spindle shaped or dendritic melanocytes diffuse distributed in the middle dermis and closely aggregated deeply pigmented melanocytes in the reticular dermis. The other three lesions were diagnosed as dermatofibromas: bland spindle shaped cells in a fibrous stroma, some cells with a storiform arrangement. The overlying epidermis was hyperplastic with acanthosis and hyperpigmentation of the basal cell layer. No mitoses were seen.

Histopathologic features of Spitzoid lesions in different age groups.

Spitz nevus is one of the most difficult melanocytic lesions to diagnose in regard of malignancy, even for experienced dermatopathologists. We analyzed 28 tumors with Spitzoid morphology from 15 children (three little children 2-4-year-old, 12 peripubertary children 9-17-year-old) and 13 adults; there were 21 Spitz nevi, five atypical Spitz tumors and two Spitzoid melanomas in order to establish the diagnostic value of several morphologic parameters in different age groups. No significant differences in respect of age and/or tumor type occurred for gender, location, dimension, symmetry, sharp lateral demarcation, junctional nests orientation, adipose tissue extension, side-to-side cytologic symmetry, uniform melanin deposits, nuclear pleomorphism, presence of mitoses, inflammation and epidermal alterations. Pagetoid growth and/or melanin deposits in the keratin layer were significantly higher in little children. In adults, presence of isolated cells within the lateral margins allows differentiating Spitz nevus from atypical Spitz tumor and Spitzoid melanoma. Deep located mitoses were statistically associated with Spitzoid melanoma in adults. Ulceration was statistically more frequent in peripubertary patients than in adults, probably due to trauma. In conclusion, presence of worrisome morphologic features (pagetoid growth, isolated cells within the lateral margins or ulceration) is correlated to patient's age and less to tumor type; there is no unique morphologic feature to relay on when evaluating a Spitzoid tumor, the final diagnosis being the results of interpretation of multiple clinical, morphologic, immunohistochemical and molecular data and not least dermatopathologist's personal experience.

Epidemiological and morphological data of ocular melanocytic lesions.

Ocular melanocytic lesions comprise a spectrum of lesions ranging from benign nevi to invasive melanoma. Clinical and histopathological appearance of conjunctival lesions ranges from freckle to lentigo and to nevi. Between these types, conjunctival nevi and conjunctival melanosis are the most frequent. Conjunctival and uveal melanocytes are derived from the neural crest, as their cutaneous counterparts, whereas the pigment epithelial melanocytes are derived from the neuroepithelium or the layers of the optic cup. Melanomas can develop in one of several places within the eye, and can be divided in uveal melanomas and conjunctival melanomas. The purpose of the study was to investigate the epidemiological and morphological data of ocular melanocytic lesions, especially intraocular melanoma, through analysis of the ocular biopsies received in the Department of Pathology, Emergency City Hospital, Timisoara, Romania, for the period of five years. We did not observed any gender predilection neither in benign nor in malignant tumors. In our study, whatever the tumor location was, the most common type of melanomas was mixed with both, epithelioid and spindle cells. In some cases, immunohistochemical investigations are useful to appreciate the benign or malignant character of the tumor.

Hand, foot and mouth disease--outbreak in Romania?

Hand, foot and mouth disease (HFMD) is a viral illness usually occurring during the summer months in children younger than 5 years of age. In the North-East area of Romania the incidence is usually low, each dermatologist reporting 1-2 cases or even less per year. The diagnosis is usually based on the characteristic clinical aspect: vesicles and papules on the hands and feet and superficial oral ulcers. HFMD is typically a benign and self-limiting disease that resolves in approximately 7 days; in Asia there have been few reported severe cases that developed neurological complications and even death, while in certain areas of China this disease is a more and more serious public health problem. In the summer of 2012 in North-East Romania numerous cases of disease have been reported, some with atypical clinical manifestations and most of them with mild or moderate forms of disease. The present article is a discussion on one of these cases. The diagnosis was made based on lesions location and clinical appearance. An outbreak of HFMD should be confirmed by virology tests.

Spectrum of morphologic alterations of regression in cutaneous melanoma--potential for improving disease prognosis.

INTRODUCTION: Regression occurs as a complex interaction between tumor cells and host's immune response; neither biologic mechanisms, nor regression prognostic significance are deciphered to date but promising anti-cancer vaccine strategies were thus developed. METHODS: We analyzed 127 superficial spreading melanomas identifying melanoma with regression (segmentary (SR), partial (PR) and segmentary & partial (SR-PR)) or without regression (AR). Several histopathologic parameters were registered; statistical analysis was performed (level of significance P < 0.05). RESULTS: Regression was present in 52% cases, less frequently in pT4 melanomas. Ulceration and vascular invasion were similarly present in pT2-pT4 melanomas with regression and significantly less in pT1 ones; their incidence increased with stage in AR (P < 0.001). SR and SR-PR melanomas showed significantly more tumor infiltrating lymphocytes within the non-regressed tumor than AR melanomas (P < 0.05). SR melanomas presented significantly less frequent mitoses than PR (P = 0.04), SR-PR (P = 0.04) or AR ones (P = 0.03). Marked inflammation and more numerous melanophages were present regressed areas advanced stage melanomas. More numerous plasma cells were identified in advanced stages; in SR and SR-PR melanomas less numerous plasma cells were present in pT1 than in advanced stages. Vascular hyperplasia was significantly higher in SR than SR-PR cases. CONCLUSIONS: Differences in perception of regression might be the result of labeling with similar name of various processes comprising inflammation and tumor cells destruction; at least in thin melanomas, PR and SR seem to belong to different spectrum of alteration, SR bearing a more favorable potential. Further studies will be performed in order to further elucidate the mechanisms involved in regression in melanoma.

Multiple disseminated glomuvenous malformations: do we know enough?

Multiple glomuvenous malformations (GVMs), also known as glomangiomas, are uncommon entities with histological features of both glomus cells proliferation and venous malformation. A 14-year-old boy was admitted to our clinic with multiple dermal blue nodules, disseminated in different segments of the body. The patient's family history was positive for similar lesions; his mother and maternal grandmother had some asymptomatic blue nodules on their body. Histological examination showed a tumor composed of multiple caveronous vessels surrounded by glomus cells, positive for alpha smooth muscle actin, HHF35 (pan-actin), and h-caldesmon. This is a case of multiple GVMs, a rare disease caused by mutations in glomulin gene, with an autosomal dominant pattern of inheritance. The clinical and histopathological features are briefly discussed.

Has the diversity of clinical and biological manifestations of systemic lupus erythematosus a correspondent in the diversity of immune mechanisms? Observations based on a Rowell's syndrome case associated with arthritis and nephritis.

This paper draws attention to the relationship between the clinical and biological picture of SLE and the immune mechanisms of this disease. The presence, in the same patient, of erythema multiforme-like skin lesions and erythemato-squamous lesions specific for SLE together with a characteristic immune picture (speckled antinuclear antibodies (ANAs), positive anti-Ro antibodies, positive rheumatoid factor) raise the question of a relationship between the immune mechanisms in SLE and the clinical picture. A case of Rowell's syndrome is discussed: systemic lupus erythematosus diagnosed on the occasion of an erythema multiforme-like rash. Starting from this case, we analyse if the clinical and biological picture in SLE is an expression of the immune mechanisms involved in this disease. Our patient presented with speckled antinuclear antibodies, positive rheumatoid factor, anti-Ro antibodies, suggestive of Rowell's syndrome. The patient manifested rheumatoid-like articular pain and high titer rheumatoid factor. Clinically, we found erythema multiforme-like and erythemato-squamous lesions. The patient developed nephrotic syndrome (proteinuria 11.8g/24h), and renal failure (creatinine 3.08 mg/dl). The renal biopsy showed mesangial proliferative glomerulonephritis class II (ISN/RPS). Under treatment with prednisone the nephrotic syndrome evolved into remission (traces of proteinuria) and serum creatinine declined (1.03 mg/dl). The cutaneous syndrome had a spectacular evolution, too. The question is raised of the existence in Rowell's syndrome of immune mechanisms commonly encountered in SLE and a subset associated with the cutaneous erythema multiforme-like rash and pseudo-rheumatoid arthritis manifestations.

[Bone turnover markers evaluation in psoriatic arthritis]. / Evaluarea anumitor mediatori ai turnover-ului osos din artrita psoriazica.

UNLABELLED: The aim of this study was to investigate the blood level of bone turnover markers: osteoprotegerin (OPG), bone alkaline phosphatase (Bone-ALP), and receptor activator of NF-kappa B ligand (RANKL) of patients with psoriatic arthritis. METHODS: Twenty-four patients with psoriatic arthritis (CASPAR classification criteria) and twenty healthy controls were included. The OPG, Bone-ALP and RANKL levels were quantified by using ELISA method. RESULTS: Peripheral blood levels of bone turnover markers were higher in psoriatic arthritis than martors and there was a strong negative correlation between OPG-RANKL and Bone-ALP- RANKL. CONCLUSION: The OPG and Bone-ALP serum level is strongly negative related to the increase in RANKL serum level in patients with psoriatic arthritis. The increase in OPG and Bone-ALP serum level induces the production of bone matrix parallel to the bone destruction mediated by RANKL. Follow up of patients with psoriatic arthritis, by use of early determination of RANKL, OPG and Bone-ALP serum levels, and also of bone metabolism markers (they have specific role in bone remodeling), allows a precise evaluation of disease activity and, in future, could be a criteria for the initiation of specific, targeting treatment.

The biomolecular and ultrastructural basis of epidermolysis bullosa.

Transmission electron microscopy, immunoelectron microscopy, immunofluorescence and antigenic mapping have improved our understanding of the dermo-epidermal junction. We have reviewed some ultrastructural and biomolecular aspects related to the dermo-epidermal junction. In part, they are implicated in the pathogenesis of a group of hereditary disorders characterized by skin fragility, collectively known as epidermolysis bullosa (EB). These disorders could benefit in the near future from a gene therapy approach but at present genetic counseling, prenatal diagnosis and conservative treatment measures offer little real benefit to patients.

[Trichothiodystrophy and hypereosinophilic syndrome, an unusual association]. / Trichothiodystrophie et syndrome d'hyperéosinophilie, une association insolite.

We present a case of trichothiodystrophy associated with a hypereosinophilic syndrome. This case had been followed for 30 years. Trichothiodystrophy was characterized by lamellar ichthyosis, hair and nail dystrophies, kyphoscoliosis, congenital luxation of the hip. The hypereosinophilic syndrome was characterized by an itching urticaria-like eruption. Although the patient's general condition had remaining stable for 30 years, during the last year it worsened and the patient suddenly died. The authors discuss about the significance of this association.