Surgical, Dermatological and Morphopathological Considerations in the Diagnosis and Treatment of Cutaneous Lymphoproliferative Tumors, Primary CD4.

Primary cutaneous lymphomas are a heterogeneous group of T-cell (CTCL) and B-cell lymphomas (CBCL) developing in the skin and without signs of extracutaneous disease at the time of diagnosis. The term "primary small/medium CD4+ T-cell lymphoma" was changed to "primary small/medium cutaneous CD4+ lymphoproliferative disorder" due to its indolent clinical behavior and uncertain malignant potential. This paper presents a rare case of primary cutaneous lymphoma with small to medium CD4+ T-cells. A 37-year-old patient presented with a tumor in the frontal region that had occurred approximately 8-9 months earlier. The tumor had a diameter of about 8-9 mm, well demarcated macroscopically, it was round in shape, about 6-7 mm high, pink in color, firm in consistency and painless during palpation. Surgical excision of the tumor was performed with a margin of safety of 8 mm and deep to the level of the frontal muscle fascia. The histopathological examination supported the diagnosis of cutaneous lymphoproliferation with a nodular disposition in the reticular dermis and extension around the follicular epithelia and sweat glands, composed mainly of dispersed medium-large lymphocytes. Additional immunohistochemical examination was requested. Immunohistochemical examination confirmed the diagnosis of "primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder." Patient monitoring was carried out through clinical dermatological controls at 3, 6, and 12 months. After one year, a cranio-cerebral MRI was performed. For the following 5 years, an annual dermatological examination accompanied by cranio-cerebral MRI, blood count, and pulmonary X-ray were recommended. Similarly to all solitary skin lesions, the prognosis is excellent in this case, the only treatment being surgical excision.

Identifying the Sentinel Lymph Node in Patients with Cutaneous Melanoma - Preliminary Report of a Private Clinic in Bucharest.

Background: The accuracy of the staging, along with the reproductibility of intraoperative lymph car-tography, and lymph node biopsy in patients with malignant melanoma was unanimously validated in the last decade. This technique allows the discovery of lymph node micrometastses with the help of immunohistochemical methods. The goal of the present study is to present the experience of our clinic in identification and biopsy protocol of the lymph node. Methods: A year-long retrospective analysis was running between March 2019 - December 2019 con-cerning 57 patients with cutaneous melanoma on which detection and excisional biopsy of the lymph node was performed. The procedure was performed by the double method using vital dye and a ra-dio-active tracer. Demographic information was filed, as well as data on location of primary tumors, tumor histology, and radioactivity level. Results: The mean Breslow thickness of primary skin melanomas was 2.7 mm. At least one lymph node was identified in 56 of the 57 patients included in the study. Among those, 15 (26%) had at least one metastatic node. The mean number of excised lymph nodes per patient was 1.6. Conclusions: The cartography and biopsy of lymph nodes need the involvement of a complex multi disciplinary team made of nuclear medicine, surgery, and anatomopathology specialists. This way one provides both a correct staging of the patient with melanoma and access to adjuvant innovative therapies, thus considerably improving the prognosis.

Surgical Outcomes of More Than 1300 Cases of Mohs Micrographic Surgeries from a Private Mohs Clinic in Romania.

Background: Basal cell carcinoma (BCC) and Squamous cell carcinoma (SCC) are the most frequent skin cancers with a continuous increasing incidence and a cause of economic impact. Mohs micrographic surgery (MMS) is known as the gold-standard of treatment of non-melanoma skin cancer. Methods: The files of the patients treated with MMS were analysed during a 6 year period (2014-2019) and demographic information was extracted in addition to the information on tumor histology, localization of tumors, number of stages required for a complete removal of the tumors, and the evolution of the patients. We also analysed the information regarding the number and type of reconstructions performed. Results: Over the course of 6 years, 1,356 cutaneous tumors were treated in our clinic by means of MMS. BCC represented 80.5%, SCC 17.6%, and other tumors such as melanoma in situ, DFSP, Extramammary Paget's Disease - being 1.9% of the number of other treated tumors. During the period under review, only 4 cases of post-Mohs Micrographic Surgery recurrence have been recorded, with a cure rate of over 99.7%. Conclusions: Mohs micrographic surgery is an efficient treatment method in removing cutaneous carcinoma as well as tumors with special indications with a low recurrence rate therefore reducing the need of successive surgical interventions.

Direct immunofluorescence on hair follicles--present and future perspectives.

Direct immunofluorescence (DIF) is an important tool for evaluating bullous autoimmune and connective tissue disorders. We report 21 cases of pemphigus vulgaris, bullous pemphigoid and lupus erythematosus that were investigated by performing DIF on scalp hair follicles. The study was done using a simplified technique of preparing the hairs for DIF testing. The anagen hairs tested positive in pemphigus vulgaris patients while the telogen hairs were negative. In bullous pemphigoid and lupus erythematosus cases hair DIF presented negative results.Hair DIF has the potential of taking the place of skin or mucosal DIF in pemphigus patients if performed on anagen hair follicles. The technique used to perform hair DIF is important in obtaining reliable results and eliminating the possibility of generating false-negative testing. Larger studies are needed in order to validate this method.

Eosinophilic, polymorphic, and pruritic eruption associated with radiation therapy in two patients diagnosed with prostate cancer.

Key Clinical Message: We report 2 cases of EPPER diagnosed in patients who received radiation therapy and hormonal therapy for locally advanced prostate cancer. Both our patients developed this rare late toxicity, but early diagnosis and treatment of this adverse event offers a good prognosis, with no unnecessary interruptions of oncological treatment required. Abstract: Acute and late adverse events are a major problem for patients receiving radiation therapy. We describe two cases of eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy (EPPER) syndrome, a very uncommon toxicity that affects cancer patients. Both our cases were men diagnosed with localized prostate cancer and were treated with radiotherapy and hormonal therapy. They developed EPPER during and after completing the total radiation dose. Multiple tests and skin biopsies were performed in order to find a superficial perivascular lymphohistiocytic infiltrate, confirming EPPER. The patients received corticotherapy and fully recovered after this treatment. There are a few more cases of EPPER reported in the literature, but the pathogenic mechanism is still unknown. EPPER is an important side effect of radiation therapy and it is probably underdiagnosed, due to its occurrence (usually after completing the oncological treatment).

Case report: Abrikossoff's tumor of the facial skin.

Abrikossoff tumors, also known as granular cell tumors (GCT), originate from Schwann cells. The most common location is in the oral cavity, followed by the skin, but they can also be found in the breast, digestive tract, tracheobronchial tree, or central nervous system. They can affect both sexes at any age, with a higher incidence between 30 and 50 years and a slight predisposition for female sex. They are usually solitary tumors but may also be multifocal. Most of the time, they are benign, with malignancy being exceptional in <2% of cases. Clinically, they appear as solid, well-defined, painless tumors, located subcutaneously with dimensions that can reach up to 10 cm. The definitive diagnosis is based on the immunohistochemical examination, and the treatment for benign tumors consists of surgical excision. Chemotherapy or radiotherapy may be required for malignant lesions, but the treatment regimens and their benefits remain unclear. This manuscript presents the case of a 12-year-old girl with a benign GCT, located in the skin on the mandibular line.

The Characteristics of Sentinel Lymph Node Biopsy in Cutaneous Melanoma and the Particularities for Elderly Patients-Experience of a Single Clinic.

BACKGROUND: Melanoma is a malignant tumor that determines approximately 80% of deaths as skin cancer-related. The sentinel lymph node (SLN) represents the first filter of tumor cells toward systemic dissemination. The primary objective was to outline the surgical specifics of the sentinel lymph node biopsy (SLNB) technique, correlate the location of the lymph node with the radiotracer load, and identify the characteristics of older patients. METHODS: In this prospective study, 122 cases of malignant melanoma needing SLNB technique were included, between June 2019 and November 2022, resulting in 162 lymph nodes removed. RESULTS: Patients' mean age was 54.3 ± 14.4 years old, the prevalence of 70 years and older being 20.5%. The rate of positive SLN was 24.6%, with a single drainage in 68.9% of cases. The frequency of seroma was 14.8%, while reintervention 1.6%. The inguinal nodes had the highest preoperative radiotracer load (p = 0.015). Patients 70 years old or older had significantly more advanced-stage melanoma (68.0% vs. 45.4%, p = 0.044, OR = 2.56) and a higher rate of positive SLN (40.0% vs. 20.6%, p = 0.045,OR = 2.57). Melanoma of the head and neck was more common among older individuals (32.0% vs. 9.3%, p = 0.007,OR = 4.60). CONCLUSIONS: The SLNB has a low rate of surgical complications and the positivity of SLN is not related to radiotracer load. Elderly patients are at risk for head and neck melanoma, have more advanced stages, a higher SLN positivity, and a greater rate of surgical complications.

A Case of Multinucleate Cell Angiohistiocytoma with New Reflectance Confocal Microscopy Findings.

Multinucleate cell angiohistiocytoma (MCAH) is a rare, benign, vascular or fibrohistiocytic tumor usually presenting as single or multiple, reddish-brown papules mostly affecting the limbs and dorsum of the hands of middle-aged females. Since 1985, relatively few MCAH cases have been reported. In vivo reflectance confocal microscopy (RCM) findings of MCAH have never been described. We report a case of MCAH with new non-invasive imaging findings through RCM in correlation with dermoscopy and histopathology. A 66-year-old woman with an unremarkable family and personal history of an atypical nevus presented with a lesion on her right breast. It had appeared 12 months earlier and progressively enlarged. Physical examination revealed a 20 × 11.6 mm, non-tender, reddish-brown maculo-papular lesion with blurred margins. Dermoscopy showed diffusely arranged reddish areas, coalescing whitish patches, truncated and dotted vessels, and a peripheral brown reticulated pattern. RCM revealed a poorly outlined lesion with a normal honeycomb pattern, numerous vessels at the dermal-epidermal junction, and isolated, large, mildly reflective, bizarre structures with angulated edges. These findings correlated well with histological features, which established the diagnosis of MCAH. Even though histopathology remains the gold standard in the diagnosis of MCAH, non-invasive tools such as RCM can help rule out other entities, therefore reducing surgery-associated morbidity.

Poroid Hidradenoma: Dermoscopic and In Vivo Reflectance Confocal Microscopic Description.

Poroid hidradenoma (PH) is a rare, benign adnexal neoplasm usually presenting as a solitary, well circumscribed, asymptomatic papule or nodule that appears reddish and is occasionally tender. Since 1990, only a few cases of PH have been reported. We present a case of PH on the medial surface of the thigh and describe, for the first time, the dermoscopic and reflectance confocal microscopic (RCM) features in correlation with histology. A 67-year-old woman with unremarkable family or past medical history presented with a nodular lesion on the medial surface of the right thigh. The lesion had appeared 4 months earlier and rapidly enlarged. Physical examination revealed a 7 × 5 mm, non-tender, reddish nodule with clinically distinct margins. Dermoscopy showed central blue-grey pigmented areas, a polymorphous vascular pattern with arborizing, glomerular and hairpin vessels surrounded by white halos. RCM revealed an ovoid, well-outlined tumor, with a central area containing cells with distinctive morphologies, two types of tumor cells, tubular hypo-reflective structures, and rectilinear vessels in the stroma. These findings correlated with histological features, which established the diagnosis of PH. Even though the diagnosis of PH remains histopathological, non-invasive tools, such as RCM, can help rule out several malignancies, therefore reducing surgical-associated comorbidity.

Dysplastic nevus syndrome and pancreatic cancer: A case report.

Multiple primary cancers may occur in the same patient, with a prevalence that follows an ascendant trend. Their development is dictated by a complex interplay between a variety of factors, both patient-dependent and external. The case of a 38-year-old female patient diagnosed and treated for pancreatic cancer (PC) is presented in whom the digital dermoscopic monitoring of melanocytic nevi revealed a marked change of two nevi that acquired rapidly highly atypical features. They were surgically excised and the histopathological examination revealed two completely excised dysplastic compound nevi. Clinicians should be aware of the strong association between dysplastic nevus syndrome and PC, a malignancy associated with an extremely poor prognosis. Familial atypical multiple mole melanoma syndrome (FAMMM) predisposes to the development of melanoma, pancreatic cancer and other neoplasms. The common genetic background of PC and hereditary melanoma is discussed and the importance of regular skin checkup and screening for PC in these patients is underlined.

Anti-MDA5 Amyopathic Dermatomyositis-A Diagnostic and Therapeutic Challenge.

Clinically amyopathic Dermatomyositis (CADM) is a rare subtype of idiopathic inflammatory myositis, associated with no muscular manifestations, which is more frequent in Asian women. Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are a recently discovered type of specific autoantibodies associated with myositis. The anti-MDA5 DM was initially described in Japan and later it was discovered that the target antigen was a protein implicated in the innate immune response against viruses, that is encoded by the melanoma differentiation-associated gene 5. Anti-MDA5 DM is characteristically associated with distinguished mucocutaneus and systemic manifestations, including skin ulcerations, palmar papules, arthritis, and interstitial-lung disease. Patients with anti-MDA5 positivity have a high risk of developing rapid progressive interstitial-lung disease (RP-ILD), with a poor outcome. As a result, despite high mortality, diagnosis is often delayed, necessitating increased awareness of this possible condition. Despite a severe course of lung disease and an increased mortality rate, there is currently no standard treatment. Recent insights based on observational studies and case reports support combined therapy with immunosuppressive drugs and corticotherapy, as soon as the symptoms appear. The aim of this paper is to describe anti-MDA5 DM, focusing on the recent literature about the unique clinical manifestations and therapeutic options, starting from a severe clinical case diagnosed in our Rheumatology Department.

Preoperative Evaluation through Dermoscopy and Reflectance Confocal Microscopy of the Lateral Excision Margins for Primary Basal Cell Carcinoma.

Complete removal of malignant skin lesions with minimal impact on the aesthetic and functional aspects is the ideal of every dermatologic surgeon. Incomplete surgical excisions and tumor recurrences of basal cell carcinomas (BCC) commonly occur due to the subclinical extension of tumor lateral margins. Presently, the lateral excision margins for BCC cannot be objectively assessed preoperatively, dermoscopy proving to be relatively inefficient in this respect. The question is whether BCC lateral excision margins can be precisely determined preoperatively through the use of complementary non-invasive imaging techniques such as dermoscopy and reflectance confocal microscopy (RCM), thus permitting the complete removal of the lesion in a single stage, estimation of the post-excisional defect, and planning an appropriate reconstruction, especially in medical centers where Mohs micrographic surgery is not available. We present the results of a prospective, histopathologically controlled study designed to determine the feasibility of preoperative, non-invasive, in vivo evaluation of the lateral excision margins for primary basal cell carcinoma, through dermoscopy and RCM.

Modified Mohs Micrographic Surgery in Lentigo Maligna Treatment: A Series of Six Cases.

The surgical approach to lentigo maligna is a challenge to dermatologists, given its clinical and histopathological particularities. Staged excision with paraffin-embedded, permanent sections for histopathological evaluation of surgical margins is an effective treatment of lentigo maligna because it enables complete excision of the tumor, at the same time preserving maximum amount of healthy tissue. We report a case series of 6 patients diagnosed with lentigo maligna who underwent this procedure in our Institution and we describe the procedure we used. Complete excision of the tumors was achieved with one to three levels, with margins of excision ranging from 2 to 8 mm. There were no local recurrences at the median follow-up of 16 months, obtaining 100% cure rate with this technique. These are comparable with the margins and number of levels of excision described in previous case series reported in the literature. The technique described herein for the treatment of lentigo maligna provides excellent cure rates for this type of cutaneous malignancy notorious for its challenging management.

Glycogen-rich clear cell carcinoma of the breast with solid papillary pattern: Two cases with heterogeneous clinicopathological features.

Invasive breast cancer is a heterogeneous disease, both in its histopathological classification and clinical course. Glycogen-rich clear cell carcinoma of the breast is an extremely rare subtype of invasive breast carcinoma, accounting for up to 3% of all breast carcinomas. The tumor is composed of polygonal cells with abundant clear cytoplasm containing glycogen and has a very controversial prognosis. Solid papillary pattern is an uncommon morphological variant of breast carcinoma which is associated with indolent behavior in the absence of an invasive component. To date, there are only three cases of glycogen-rich clear cell carcinoma with solid papillary pattern reported in the English literature. In this article, we present two cases of glycogen-rich clear cell carcinoma of the breast, encountered in our daily clinical practice over a period of 5 years (2015-2020) and perform a brief review of currently published literature. Unlike most cases of glycogen-rich clear cell carcinoma documented to date, follow-up of our case featuring solid papillary pattern revealed extremely favorable clinical outcome, suggesting a better prognosis for tumors with this morphology.

Melanonychia - Clues for a Correct Diagnosis.

Melanonychia represents a brown to black discoloration of the nail plate that may be induced by benign or malignant causes. Two main mechanisms are involved in the appearance of melanonychias, i.e., melanocytic activation and melanocytic hyperplasia. The distinction between the two can be made based on the medical history of the patient, the clinical picture, dermoscopy, and histopathological examination and is essential for the adequate management of the patient. We review the main causes of melanonychia, with emphasis on the clues to the diagnosis of subungual melanoma.

Juvenile Colloid Milium: Case Report and Literature Review.

Juvenile colloid milium (JCM) is a rare, chronic, benign but cosmetically disturbing degenerative dermatosis, characterized by the appearance of translucent papules on sun-exposed areas before puberty. The juvenile form of colloid milium is thought to be caused by an inherited susceptibility to ultraviolet (UV) light, transmitted in an either autosomal dominant or recessive manner, eventually leading to keratinocyte degeneration. The prevalence of JCM is unknown due to the scarcity of case reports. This paper describes the case of a 10 years old male patient diagnosed with JCM which, according to the information available so far, is the first such case reported in Romania.

Epidermolysis Bullosa Acquisita: A Case Report of a Rare Clinical Phenotype and a Review of Literature.

Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal bullous disorder of the skin and mucous membranes. The disease results from the production of immunoglobulin G (IgG) antibodies against type-VII collagen, a major component of anchoring filaments in the dermal-epithelial junction. The disease has two major forms of presentation: the classical (non-inflammatory) type and the inflammatory type. Classical EBA is mainly characterized by the following features: development of non-inflammatory tense blisters on trauma-prone areas, multiple milia cysts, minimal or no inflammation findings on histopathology. Alternatively, inflammatory EBA is defined by widespread inflammatory blistering eruptions and a neutrophil-rich inflammatory infiltrate on standard histopathology. In both cases, specialized immunopathological findings are further required to establish an accurate diagnosis. In this article, we present an atypical case that shares features of both inflammatory and non-inflammatory forms of EBA. The case also serves to review and synthesize current concepts on the etiopathogenesis, diagnosis, and treatment of this extremely rare disease.

Interstitial Granulomatous Dermatitis (IGD).

We report the case of a 42 years old male patient suffering from skin changes, which appeared in the last 7-8 years. Two biopsies were performed during the evolution of the lesion. Both showed similar findings that consisted in a busy dermis with interstitial, superficial and deep infiltrates of lymphocytes and histiocytes dispersed among collagen bundles, with variable numbers of neutrophils scattered throughout. Some histiocytes were clustered in poorly formed granuloma that included rare giant cells, with discrete Palisades and piecemeal collagen degeneration, but without mucin deposition or frank necrobiosis of collagen. The clinical and histologic findings were supportive for interstitial granulomatous dermatitis. Interstitial granulomatous dermatitis (IGD) is a poorly understood entity that was regarded by many as belonging to the same spectrum of disease or even synonym with palisaded and neutrophilic granulomatous dermatitis (PNGD). Although IGD and PNGD were usually related to connective tissue disease, mostly rheumatoid arthritis, some patients with typical histologic findings of IGD never develop autoimmune disorders, but they have different underlying conditions, such as metabolic diseases, lymphoproliferative disorders or other malignant tumours. These observations indicate that IGD and PNGD are different disorders with similar manifestations.

Lichen Simplex Chronicus as an Essential Part of the Dermatologic Masquerade.

A 48 years old female patient had been suffering from the lesions presented for four years. They have started as small, pruritic patches which had been mechanically irritated and grew up in time. The patient had no associated comorbidities or allergies, and she was not under any medication. On physical examination, she presented one erythematous, exudative plaque, with dimensions of 2.5/4 cm, located on the proximal phalanx and interphalangeal articulation of the left thumb. All histopathological features were consistent with the diagnosis of lichen simplex chronicus. Some lesions of lichen simplex chronicus exhibit signs of pseudocarcinomatous, infundibular and sometimes eccrine ductal proliferation of keratinocytes. Although the pseudoinfiltrative aspect of the epithelial proliferation and its pronounced degree might mimic a well-differentiated lesion of squamous cell carcinoma, a lack of cellular atypia and atypical mitotic figures are features that do not support this diagnosis. On the other hand, long lasting lesions of lichen simplex chronicus may lead to alterations in the processes of keratinocyte proliferation and differentiation and eventually give rise to malignant transformation. The best treatment management is a psychodermatological approach, a combination of skin care with psychotherapy, in order to prevent relapses.

Basal Cell Carcinoma Surgery: Simple Undermining Approach in Two Patients with Different Tumour Locations.

Basal cell carcinoma (BCC) is the most common human malignancy, accounting for the majority of all non-melanoma skin cancers (NMSC). In the past several decades the worldwide incidence of BCC has constantly been increasing. Even though it is a slow growing tumour that, left untreated, rarely metastasizes, it has a distinctive invasive growth pattern, posing a considerable risk for local invasion and destruction of underlying tissues, such as muscle, cartilage, bone or vital structures. Advanced BCCs include such locally invasive or metastatic tumours. Complete surgical excision is the standard therapy for most uncomplicated BCC cases with good prognosis and cure rates. Treatment of advanced forms of BCCs poses significant therapeutic challenges, most often requiring complicated surgery, radiotherapy, and/or targeted therapies directed towards the sonic hedgehog signalling pathway (SHH). We present two cases of large BCCs located on the scalp and posterior thorax, which underwent surgical excision with clear margins, followed by reconstruction of the defect after extensive undermining of the skin.