Clinical Case Reports for the Evidence-Based Era

Neurofibromas Plexiform neurofibromas are benign tumors of the peripheral nerve sheath. They can be found as single or multiple nodules, which are part of the of the clinical picture in any type of neurofibromatosis, and can become malignant. Neurofibromas arise from Schwann cells which are part of the nerves of the skin throughout the body, nerves innervating internal organs and cranial nerves. The most characteristic symptoms include the presence of scattered, elongated, resilient subcutaneous nodules. These are fibromas, histologically resembling individual neurofibromas, appearing along the the course of peripheral nerves or cranial nerves. They most often occur on the face and neck. Sometimes they lead to massive enlargement of a limb or other part of the body (neurofibromatous elephantiasis) [1,2]. Another equally common common symptom is skin discoloration, looking resembling coffee spots ("giant café-au-lait spot"), as well as freckle-like lesions localized around the axillae and axillary pits [3]. Neurological symptoms are associated with the compression of neurofibromas on adjacent structures. The patient then complains of neuralgia of the peripheral nerves. In the literature we can find isolated cases of neurofibroma plexiformis without any association with neurofibromatosis type 1 [4-6]. Treatment of patients with plexiform neurofibromas is not well defined defined and is mainly aimed at controlling symptoms. Surgical excision is the only available therapy, as there there are no drugs that can prevent their formation or treat them conservatively conservatively. At present, the results of surgical excision are not fully satisfactory, and these procedures can be complicated due to the size, location, condition of the vessels, involvement of the neural involvement, microscopic staging and high rates of tumor re-growth [7]. It should also take into account the fact that there are known there are many causes causing tumor-like lesions to neurofibromas . These include traumatic soft tissue injuries, arthritis, tendon diseases (e.g. tendinosis, tendon sheath inflammation, tendon rupture), non-neoplastic soft tissue lesions (e.g. ganglion, bursitis, granuloma) , and, less commonly, tumors and their metastases to soft tissues [8]. Focal lesions of soft tissues soft tissues are often the cause of pain and palpable tumor mass [9]. W these cases, especially in the early stages, accurate diagnosis is crucial, to establish a diagnosis and treatment strategy. Therefore, w when confronted with a focal tumor lesion the logical seems is to follow established algorithm of procedure. First, it should provide an accurate description of the lesion in correlation with the patient's age, location, type of involved tissue, the condition of the adjacent environment. For this purpose, in addition to detailed clinical examination, ultrasound should be performed of the occupied area, and if a bony lesion is suspected then an x-ray examination in two projections with adjacent joints. The advancement of bone lesions, it is necessary to deepening diagnosis through CT examination. However, lesion limited only to soft tissues on ultrasound will require MRI diagnosis, which will more accurately visualize the infiltration by its neighborhood. If imaging studies show a high probability of proliferative disease, an important diagnostic element is to obtain material for pathomorphologic examination, taken during open biopsy or oligobiopsy and establish the histological diagnosis [10]. If the neoplastic process is confirmed, it is always necessary to X-ray/CT scan of the chest, ultrasound/CT scan of the abdomen and even even PET to exclude metastases [11]. The second stage of the implemented algorithm dictates that treatment should be planned based on the answers to the following questions: - Is the lesion likely to be a normal variant, i.e., "leave me alone, don't touch me." lesion of a benign type, requiring no further imaging or supplies, but only observation? [12] - Does the lesion have features suggestive of an aggressive nature, and then how far advanced should be treatment? [13]. The heterogeneity of the clinical picture of unidentified focal nodular lesions in the metacarpal region, the variety of available methods of diagnosis do not make the task any easier the task, both at the stage of making the initial diagnosis and during communication between members of the interdisciplinary team, who, on more than one occasion, should handle the treatment. Therefore, it seems important to cooperate on the line of orthopedist-oncologist-pathomorphologist. Two cases of isolated neurofibromatosis of the palm of the hand are described below because of their uniqueness. The second of the described cases indicated an additional possibility of postoperative treatment of the patient in the form of prolotherapy injections to improve the function of the treated limb.

Oncological treatment is associated with a high risk of malnutrition in children. Complications of treatment often prevent oral intake of food, which requires proper dietary modification and consideration of parenteral nutrition.

Breast sarcomas are rare, accounting for 1% of malignant gland tumors and less than 5% of all tumors mesenchymal neoplasms.1 The low incidence makes it difficult to conduct trials randomized clinical trials, and available data include descriptions of retrospective series and single cases. The number of known factors that increase risk of developing the disease is small. A genetic predisposition in the form of syndrome Li-Fraumeni (TP53 gene mutation) increases the risk of primary sarcomas also in the thoracic location.2 Chronic lymphedema occurring in some patients after axillary lymphadenectomy and axillary irradiation predisposes to lymphangiosarcoma in the affected arm (Stewart syndrome and Treves syndrome).3 Secondary sarcomas occasionally occur in breasts previously irradiated after breast conserving treatment (BCT), performed for breast cancer, the most common malignancy in women, and after radiation therapy administered for malignant granuloma.4 The cumulative risk of of radiotherapy-induced sarcoma (RIS) is 3.2 per 1,000 over 15 years vs. compared to 2.3 per 1,000 for primary sarcoma in a population without radiation therapy.5 Compared to women who were not irradiated, patients treated with radiation therapy for breast cancer, the risk of developing radiotherapy-induced hemangiosarcoma (radiotherapy-induced angiosarcoma, RIA) is five times higher 6 , in general, however, the possibility of of developing angiosarcoma after radiation therapy is low and, according to the literature literature, it is 0.03 - 0.2% in more than 10 years of follow-up.7,8 It should be clearly emphasized the benefits enjoyed by women with breast cancer due to radiation, an obligatory part of breast-saving treatment.9 There has been no correlation of the incidence of RIS with the use of chemotherapy.10 For the The diagnosis of radiotherapy-induced sarcoma can be made using criteria proposed by Cahan in 1948,11 as interpreted by Kirova15 (At that time, Cahan described more than a dozen cases of bone sarcomas in patients irradiated according to the treatment standards of the time for benign lesions and bone tuberculosis, the first point in the original description was the non-neoplastic nature of the lesion treated with radiation therapy)11: 1. History of treatment with irradiation 2. asymptomatic latency period between two cancers lasting several years 3. occurrence of sarcoma in a previously irradiated area, 4. Histopathologic confirmation of sarcoma as a second neoplasm.10,11,15 However Cahan described the latency period as "relatively long," amounting to more than 5 years in his paper, the literature a case has been described that appeared before a year, also described as a RIS (RIA).12 Among the histopathological types diagnosed among secondary sarcomas include angiosarcoma, hemangiosarcoma, leiomyosarcoma, malignant fibrous histiocytoma, liposarcoma, and fibrosarcoma. Also described were chondrosarcoma and osteosarcoma. RIS develop most often in the chest wall, less often in the parenchyma of the of the irradiated breast.10 The method of choice for patients with for breast sarcomas is excision of the tumor with a margin of healthy tissue. While in the case of primary sarcomas, follow-up treatment after sparing surgery often consists of irradiation of the operated area, when treating patients with for sarcoma occurring in a previously irradiated area, repeat radiotherapy of the of the same area is not recommended. The optimal type of treatment in such a case is mastectomy in this case.

Lung cancer accounts for the largest number of cancer deaths worldwide [1]. Despite advances in treatment, incidence and mortality rates continue to rise. A 2018 GLOBOCAN analysis reported 2.09 million new cases of lung cancer and 1.76 million deaths from lung cancer worldwide [2]. There are two main histological types: small cell lung cancer (DRP) and non-small cell lung cancer (NDRP). NDRP accounts for about 85% of all lung cancer cases. It includes various subtypes such as adenocarcinoma, squamous cell carcinoma and large cell carcinoma. The most common subtype is adenocarcinoma accounting for 45% of NDRP cases. The most important risk factor for developing lung cancer is smoking, especially among the male population. The use of filtered cigarettes, which reduce the amount of tar entering the lungs, correlates with an increase in the incidence of lung adenocarcinoma, which is associated with stronger inhalation of carcinogens into the fine airways. Other compounds that may have an effect on cancer development are asbestos, radon, nickel, cadmium, chromium, silica and arsenic. The development of molecular studies at the beginning of the 20th century made it possible to identify the genetic basis of the disease by demonstrating the presence of mutations or rearrangements of TP53, MYC, BCL2 genes in small cell carcinoma and EGFR, KRAS, MET, BRAF, NTRK, ROS1, ALK, RET, PIK3CA genes in non-small cell carcinoma [3]. The percentage of non-squamous NDRP patients with mutations in the gene for the epidermal growth factor receptor (EGFR) is 10-15 (in Caucasian patients) to more than 40% (in Asian patients) [4]. A deletion in exon 19 and a substitution at codon 858 (L858R) in exon 21 account for 80-90% of mutations within the tyrosine kinase coding domain of the EGFR gene [4]. Lung cancer manifests as cough, hemoptysis, chest pain, shortness of breath and/or hoarseness. In the case of adenocarcinoma, brain metastases manifesting as headache, vomiting, visual field disturbances, seizures or neurological deficits are common. After appropriate laboratory and imaging tests and histopathological evaluation, it is possible to assess the histological type and stage of the cancer. Depending on the patient's general condition, tumor stage and concomitant diseases, different treatment methods are used. For low-grade cancer (stages I, II and IIIA), surgery is used, often in combination with chemotherapy and radiation therapy. For stage IIIB patients, the therapy of choice is chemoradiotherapy, and if chemoradiotherapy is not available, the treatment is the same as for patients with generalized NDRP. Therapy for patients with distant metastases (stage IV) is aimed at reducing the discomfort and symptoms of progressive disease and prolonging life. For this purpose, chemotherapy, immunotherapy or molecularly targeted therapy are used [5]. Molecularly targeted therapy for lung cancer with EGFR gene mutations is made possible by the use of tyrosine kinase inhibitors (IKTs). IKTs inhibit intracellular phosphorylation of EGFR which leads to the arrest of cell differentiation, proliferation and angiogenesis. EGFR IKTs are divided into three generations. Erlotinib and gefitinib are the first-generation reversible IKTs. They are effective in the presence of the most common mutations in exon 19 and 21. Second-generation irreversible IKTs, which include afatinib and dacomitinib, show a broader spectrum of action. They block the transmission of signals formed by ErbB1 (EGFR), ErbB2 (HER2), ErbB3 and ErbB4 receptors, and can be effective in the presence of rare mutations in exons 18, 19, 20 and 21. It is possible to acquire resistance to first- and second-generation IKTs. Ozymertinib, an irreversible third-generation IKT, by acting on cells with the T790M mutation in exon 20 of the EGFR gene, overcomes resistance to treatment with older-generation EGFR IKTs, but can also be used in 1st-line treatment in NDRP patients regardless of the type of mutation in exons 18-21 of the EGFR gene [6]. The global COVID-19 pandemic poses a therapeutic challenge to healthcare, especially among oncology patients. A retrospective analysis from Wuhan showed that the risk of COVID-19 infection was 2.31 times higher among cancer patients than in healthy individuals. Smoking, age, male gender, cancer status, poor performance status (≥2 on the ECOG scale) and treatment with hydroxychloroquine with azithromycin were risk factors for increased 30-day mortality among COVID-19 patients [7]. Hospital visits during the pandemic and the use of immunosuppressive medications are major contributors to COVID-19 infection in lung cancer patients [8]. A study conducted in China, showed that NDRP patients over 60 years of age are particularly vulnerable to COVID-19 infection and a more severe course of the disease. Many respiratory symptoms in COVID-19 i.e. shortness of breath, cough, fever overlap with those of lung cancer. This creates a difficulty in differential diagnosis between the two disease entities. The diagnosis of COVID-19 is usually made on the basis of clinical history and PCR test and/or antigen test in a sample from nasopharyngeal secretions. Recognition of typical lesions seen on chest CT scan is also helpful. Multifocal opacities of the frosted-glass type with predilection for the lower lobes are present in 75% of patients [9]. A study conducted in New York among lung cancer patients with concurrent SARS-CoV2 infection showed the need for hospitalization in 62% of patients, 21% of whom required ICU hospitalization. Of the 102 patients participating in the study, 25% died. Survival was more dependent on the comorbidity of COPD (chronic obstructive pulmonary disease) and smoking than on tumor histology or PD-L1 (programmed death ligand 1) expression on tumor cells [10].