Are There Any Differences in the Healing Capacity between the Medial Collateral Ligament's (MCL) Proximal and Distal Parts in the Human Knee? Quantitative and Immunohistochemical Analysis of CD34, α-Smooth Muscle Actin (α-SMA), and Vascular Endothelial Growth Factor (VEGF) Expression Regarding the Epiligament (EL) Theory.

The human knee is a complex joint that comprises several ligaments, including the medial collateral ligament (MCL). The MCL provides stability to the knee and helps prevent its excessive inward movement. The MCL also has a thin layer of connective tissue known as the epiligament (EL), which adheres to the ligament. This unique feature has drawn attention in the field of ligament healing research, as it may have implications for the recovery process of MCL injuries. According to the EL theory, ligament regeneration relies heavily on the provision of cells, blood vessels, and molecules. The present study sought to compare the expression of vascular endothelial growth factor (VEGF), CD34, and α-smooth muscle actin (α-SMA) in healthy knees' proximal and distal MCL segments to better understand how these proteins affect ligament healing. By improving the EL theory, the current results could lead to more effective treatments for ligament injury. To conduct the present analysis, monoclonal antibodies were used against CD34, α-SMA, and VEGF to examine samples from 12 fresh knee joints' midsubstance MCLs. We identified a higher cell density in the EL than in the ligament connective tissue, with higher cell counts in the distal than in the proximal EL part. CD34 immunostaining was weak or absent in blood vessels and the EL, while α-SMA immunostaining was strongest in smooth muscle cells and the EL superficial layer. VEGF expression was mainly in the blood vessels' tunica media. The distal part showed more SMA-positive microscopy fields and higher cell density than the proximal part (4735 vs. 2680 cells/mm2). Our study identified CD34, α-SMA, and VEGF expression in the MCL EL, highlighting their critical role in ligament healing. Differences in α-SMA expression and cell numbers between the ligament's proximal and distal parts may explain different healing capacities, supporting the validity of the EL theory in ligament recovery.

A Case of Tracheal Stenosis as an Isolated Form of Immunoproliferative Hyper-IgG4 Disease in a 17-Year-Old Girl.

Immunoglobulin G4-related disease (IgG4-RD) is a lymphoproliferative disease which is described almost exclusively in adults. There are only a few pediatric patients who have been observed with this disorder. Here, we describe a rare case of IgG4-RD in a 17-year-old girl with a single manifestation-tracheal stenosis without previous intubation or other inciting event. She had mixed dyspnea and noisy and weakened breathing. Immunoproliferative hyper-IgG4 disease was diagnosed, based on elevated serum IgG4 and histological findings. Until now we have chosen to treat the girl only with corticosteroids with a good response so far. The general condition as well as the respiratory function are regularly monitored. The tracheal involvement of IgG4-RD is uncommon. Nonetheless, it is a manifestation that should be included in the differential diagnosis of tracheal stenosis.

A Series of Patients with Kaposi Sarcoma (Mediterranean/Classical Type): Case Presentations and Short Update on Pathogenesis and Treatment.

BACKGROUND: Kaposi's sarcoma was first described in 1872 by Moritz Kaposi. To date, it is considered a malignant disease is originating from the endothelial cells of the lymphatic vessels believed to be infected with HHV-8. The current classification defines four major epidemiological forms of Kaposi's sarcoma: classical, endemic, AIDS-associated, and iatrogenic. CASE REPORT: A 90-year-old male is presented with multiple plaques- and tumour-shaped brown-violet formations located on an erythematous-livid base in the area of both feet and both shanks. Two samples were taken from the lesions on the skin of the shanks, with histopathological examination and the subsequent immunohistochemistry showing Kaposi's sarcoma. CONCLUSIONS: Kaposi sarcoma is a disease that causes difficulties both in diagnostic and therapeutic respect. The only sure way to determine the correct diagnosis is immunohistochemical staining with the anti-HHV8 antibody. Despite the wide range of systematic and local treatment options, there is still no unified algorithm and a unified strategy for the treatment of Kaposi's sarcoma.

Eruptive Basaliomas: "Why we have to Perform Surgery?" Or Said Otherwise: "Catch The Metatypical!"

BACKGROUND: Keratinocyte cancers are malignant diseases with a broad incidence of spread which tends to increase during the last couple of decades. The solar radiation plays a dominant role in the occurrence of BCC, but certain genetic phenotypes appear to be risky from an etiological point of view. Metatypical basal cell carcinoma (MTBCC) is a rare variant of BCC which combines the clinical and histological characteristics of BCC and SCC. Clinically they are indistinguishable from the conventional BCC, and only the histological examination can differentiate them. The MTBCC is a histological subtype which is considered more aggressive due to its ability to produce local recurrences or distant metastases. CASE REPORT: We present a 44-year old patient with multiple BCCs disseminated on the face and body. The biopsy established mixed type histology: three metatypical and four solid BCCs. The lesions were removed via elliptical excision with a field of operational security of 0.5 cm in all directions. CONCLUSIONS: The eruptive (multiple) BCCs are a challenge about the choice of a therapy option. This is because clinically completely identical tumours show different histopathological characteristics, namely those with a tendency to metastasise. Having in mind one of the hypotheses of metatypical BCC emergence - the improper or inadequate radiotherapy (as a choice of therapy) could trigger the transition of a conventional tumour to a metastasising one, the surgical treatment appears to be the most secure treatment method.

Primary Cutaneous CD30+/ALK- ALCL with Transition into sALCL: Favourable Response after Systemic Administration with Brentuximab Vedotin! Unique Presentation in a Bulgarian Patient!

BACKGROUND: Modern drugs could sometimes be a good solution even to problematic patients. The cutaneous and systemic forms of the CD30 positive anaplastic large T-cell lymphoma could often be described as a suitable target for therapy with Brentuximab vedotin. CASE REPORT: We present the first case of a Bulgarian patient with a histologically confirmed primary cutaneous T-cell CD30+/ALK- large anaplastic cell lymphoma-cALCL (therapeutically resistant to therapy with Methotrexate, radiation therapy and systemic corticosteroid therapy) who was successfully treated with Brentuximab vedotin. In several years, the patient has developed a comparatively fast skin progression as well as an initial systemic one which impacts inguinal and mediastinal nodes. After the implementation of 4 therapy cycles with Brentuximab vedotin, complete regression of the described by previous hospitalisations lymph nodes as well as 80% reduction of the cutaneous and subcutaneous located tumour formations were observed. CONCLUSION: The therapy of CD30+/ALK- anaplastic large T-cell lymphoma is a significant challenge for oncologists and dermatologists because it requires maximally efficient and minimally traumatic treatment in parallel. Therapy with Brentuximab is a new direction which shows extremely good clinical results and can be applied to the cutaneous as well as to the systemic form of anaplastic large-cell CD30 positive lymphoma. The key element by treatment with Brentuximab is suppression of the CD30- expression which, in turn, could be the cause of relapses. On that ground, patients with these lymphomas should be strictly monitored.

Successful Craniotomy for Advanced Basal Cell Carcinomas with Cranial Bone Invasion and Dura Mater Infiltration - Unique Presentation in a Bulgarian Patient.

BACKGROUND: Basal cell carcinomas (BCC) located in the sun-exposed regions are a serious therapeutic challenge. Therefore early diagnosis and adequate therapy should be of a high priority for every dermatologic surgeon. CASE PRESENTATION: We are presenting a patient with multiple BCCs, located on the area of the scalp, who had been treated several years ago with electrocautery and curettage after histopathological verification. However, the last few years the tumours have advanced, infiltrating firstly the tabula external and a year later the tabula interna of the cranium. A computed -tomography (CT) imaging and radiography of the skull were performed to reveal the definite tumour localisation, needed for planning an one - step surgical intervention. Both of the instrumental examinations confirmed the existence of osteolytic tumour lesions. Craniotomy with precise removal of the BCCs infiltrating the cranial bone in all of its thickness was performed. Partial resection of dura mater was also performed also because intraoperative findings established the involvement of the dura. Histopathological verification revealed bone and dural invasion with clean resection margins. The bone defect was recovered with hydroxyapatite cement. Reconstruction as the shape of the skull was carefully modified and adapted to its initial size and form. Layered closure of the skin and soft tissues were performed after the complete removal of the BCCs. The postoperative period had no serious complications. CONCLUSION: Precisely managed therapy of BCC is curative in most of the cases as it ensures good prognosis for the patient.

Bullous Tinea Incognito in a Bulgarian Child: First Description in the Medical Literature!

For the first time in the world medical literature, we describe a rare form of cutaneous dermatophytosis - a bullous form of Tinea incognito, classified by clinical picture, histopathological findings and an isolated infectious agent from the microbiological culture. After a thorough review of Medline/PubMed's relevant literature, we could not find similar cases of patients with Tinea incognito who are clinically presented with bullous lesions at the same time. Local application of corticosteroids in infants with unknown lesions may lead to progression of the underlying disease and may cause some serious problems in differential diagnosis aspect, while the clinical expression remains completely masked. Exactly for this reason, right at the beginning of the clinical complaints, a skin biopsy should be obligatorily performed in parallel with microbiological swabs. If there is no improvement after the local corticosteroid application, then diagnosis revision and change of the strategy of clinical behaviour would be appropriate to be done. The systemic treatment that we performed with Fluconazole 50 mg in combination with the local antimycotic agent for a 2-week period led to complete remission.

Sarcoidosis in A. C. Milan (1899)?

The pathogenesis, diagnosis and therapy of sarcoidosis as an autonomous disease are subjects of spirited discussions, which haven't found definitive conclusion yet. Distinguishing between sarcoidosis and sarcoid-like reactions (sarcoid - type granulomas) is not currently a medical "gold standard" and is not implemented in clinical practice. This leads to 1) misinterpretation of numerous available data; 2) difficulty in the interpretation of other unverified data, which is often followed by 3) inappropriate or inadequate therapeutic approach. Similarly to many other diseases, in sarcoidosis and sarcoid - types of reactions the concept of personalised approach and therapy should also be introduced. This methodology of clinical guidance is difficult, complex and not always achievable in the current medical status and relations (doctor-patient relationship; financial factor; time factor). It is appropriate to note that in some cases the guidelines or the so-called standards are neglected or not possible to put into practice with the aim of better therapeutic practices and strategies, as well as the achievement of optimal final clinical results (especially in patients with sarcoid granulomas). The sarcoid granuloma, even when it is sterile, should not be considered as the equivalent of sarcoidosis, i.e., sarcoidosis as an autonomous disease. Sure enough, exactly because of this fact, the personalised approach should not be an exception, but it has to gradually become a rule in medical practice. When clinical decisions are conformed to some of the latest modern concepts, officialised in the international databases, often the achieved results can be much better. We present a patient with a tattoo of AC Milan (1899) on his right arm, who subsequently developed localised sterile sarcoid granulomas in the area of the tattoo. Later the process became generalised on his whole body's skin, lungs and lymph nodes. It is unclear for the moment whether this condition should be interpreted as sarcoidosis as an autonomous disease or, instead, as a sarcoidal type of reaction with subsequent generalisation due to cross-reactivity against antigens present in other tissues with similarities to the exogenous pigments. Following the modern concepts regarding the pathogenesis of these two conditions, we introduced, in this case, an innovative, non-standard approach: 1) systemic and local immunosuppressive therapy, combined with 2) recommеndation for immediate surgical excision of the tattoo to remove the possible trigger of molecular and antigen mimicry.

Mucoepidermoid Carcinoma (MEC) of Parotid Gland with Massive Cutaneous Involvement: Bilateral Pedicle Advancement Flap (U - Plasty) As Adequate Surgical Approach.

Neoplasms of the major and minor salivary glands are morphologically and a clinically diverse group of neoplasms which lead the clinician to diagnostic and management challenges. This article aims to report a case of mucoepidermoid carcinoma in 83 - year - old woman who presented in the dermatology clinic with a tumour mass in the left auricular area. The patient complained of pain and abnormal bleeding of the mass. The lesion was examined, and surgical treatment was performed. A tumour was extirpated, and partial resection of both the parotid gland and the sternocleidomastoid muscle was done. Lymphatic dissection was performed. Post recovery was uneventful with no functional defects and abnormalities. The pathohistological result confirmed the diagnosis of mucoepidermoid carcinoma of the parotid gland with massive infiltration of the skin and the subcutaneous tissue. Lymph nodules with total metastasis of mucoepidermoid carcinoma and capsular invasion were additionally presented. Postoperative radiation therapy was planned.

Small Dysplastic Congenital Melanocytic Nevi in Childhood as Possible Melanoma Imitators.

Small pigmented lesions in children can represent a significant diagnostic challenge. If the diagnostic features and therapeutic approach are relatively well established in large and giant nevi, there is still much controversy regarding small and intermediate-sized congenital pigmented lesions that can lead to significant diagnostic challenges, both clinically and dermoscopically, and consequently to difficulty in defining the optimal approach in such cases. Although dermoscopy can be useful in the diagnosis of pigmented lesions, the diversity of clinical and dermoscopic features of pigmented nevi in children usually hinder the differentiation between them and melanoma. Histological findings after resection often show surprising results that do not correspond either to the clinical nor the dermoscopic features. With the present case, we want to emphasise the variable natural behaviour of melanocytic lesions in children, which sometimes leads to unnecessary surgical excisions, which should be avoided in pediatric patients.

Rosai-Dorfman disease involving gallbladder and liver-Report of a case.

INTRODUCTION: Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare histiocytic disorder of unclear etiology. Lymphadenopathy commonly affects the lymph nodes of the neck and the head, but extranodal involvement has been observed too. PRESENTATION OF CASE: We describe an unusual case of RDD with involvement of the gallbladder, liver and cystic lymph node, clinically manifested as an exacerbated cholecystitis. The patient underwent a cholecystectomy with atypical liver resection because the finding was macroscopically suspected of gallbladder cancer. The diagnosis of RDD was confirmed by immunohistochemical study. DISCUSSION: Histological features of RDD include histiocytic proliferation, emperipolesis and positive immunostaining for S-100 protein and typically negative for CD1a. Gastrointestinal localization of RDD, especially in the liver and pancreas, is extremely rare. Typically, the liver is affected as a part of systematic spread of RDD. We have not found reports for involvement of the gallbladder. CONCLUSION: The presented case is valuable due to its rarity and difficulty in differential diagnosis.

Germ cell tumor located in the midline of the anterior neck.

Primary germ cell tumors involving midline of the anterior neck are extremely rare. Here we report a 68-year-old male who was operated due to a mass lesion in the anterior neck with infiltration of the isthmus of the thyroid gland. Histopathological examination revealed a germ cell tumor with extragonadal localization in the anterior neck infiltrating the isthmus of the thyroid gland.