The genetic etiology and the contribution of rare genetic variation in multiple sclerosis (MS) has not yet been elucidated. Although familial forms of MS have been described, no convincing rare and ...penetrant variants have been reported to date. We aimed to characterize the contribution of rare genetic variation in familial and sporadic MS and have identified a family with two sibs affected by concomitant MS and malignant melanoma (MM). We performed whole exome sequencing in this primary family and 38 multiplex MS families and 44 sporadic MS cases and performed transcriptional and immunologic assessment of the identified variants. We identified a potentially causative homozygous missense variant in NLRP1 gene (Gly587Ser) in the primary family. Further possibly pathogenic NLRP1 variants were identified in the expanded cohort of patients. Stimulation of peripheral blood mononuclear cells from MS patients with putatively pathogenic NLRP1 variants showed an increase in IL-1B gene expression and active cytokine IL-1β production, as well as global activation of NLRP1-driven immunologic pathways. We report a novel familial association of MS and MM, and propose a possible underlying genetic basis in NLRP1 gene. Furthermore, we provide initial evidence of the broader implications of NLRP1-related pathway dysfunction in MS.
Acromegaly and gigantism are hormonal disorders which develop as a consequence of chronic growth hormone hypersecretion. The prefix pseudo- is used to describe a certain clinical condition without a ...clearly proven characteristic of pathophysiological mechanism and basic biochemical features; pseudoacromegaly or acromegaloidism match the definition from above. In this case reports, we will try to provide a concise overview of diagnostic evaluation of acromegaloid physical appearance, while discussing two cases of patients who have similar clinical acromegaloid features as the first sign of the disease but have completely different etiologic backgrounds of their acromegalic appearance. The first case is of a 57-year-old male who presented with a marked acral growth and coarse facial features, but the diagnosis of secondary amyloidosis caused by multiple myeloma was confirmed just after biopsy of tongue and buccal mucosa. The second case is that of a 63-year-old male with an acromegaloid appearance caused by ectopic secretion of GH secreting lung carcinoma. The early diagnosis of ectopic acromegaly and pseudoacromegaly is still a challenging process. The key task is to confirm the GH axis abnormalities and establish the underlying disease, as a crucial step for faster treatment and need to avoid unnecessary therapeutic procedures to decreased mortality and improved quality of life.
Metastatic tumors to the oral cavity are uncommon, representing approximately 1% of all cases of oral malignant lesions even when a metastatic disease is present. The 53-year-old female is presented ...complaining of abdominal pain, weight loss, and a loose stool recurring not more than three times per day. A computed tomography (CT) scan of the abdomen showed a retroperitoneal mass expanding along the body of the pancreas. Colonoscopy and gastroscopy with a gastric mucosa biopsy showed a normal result. After laparoscopic surgery, the primary site of adenocarcinoma was not confirmed. The patient was referred to the Maxillofacial Surgery Clinic with pain, swelling, and occasional bleeding around the lower right second mollar. Immunohistochemicaly, the tumor cells were positive for Cytokeratin (CK) 19, Cytokeratin (CK) 7, and homebox protein (CDX-2), which are highly sensitive markers of pancreatobiliar cancer. Therefore, the patient was diagnosed with pancreatic carcinoma. This report describes a rare metastasis of malignant pancreatic tumor to the lower right gingiva and highlights the importance of immunohistochemical examination and how it helped identify both the origin and the nature of gingival neoplasm.
Kaposi’s sarcoma is a neoplasm of endothelial cells. That vascular tumor is usually limited to the skin, but it may involve mucous membranes, visceral organs, and lymph nodes. Serological evidence ...has shown that human herpesvirus 8 infection is required for the development of Kaposi’s sarcoma. Chronic lymphocytic leukemia is the most common leukemia all over the world. Increased skin cancer risk has been reported for patients with chronic lymphocytic leukemia. The relation between these two pathologies has not yet been clarified. We report a case of Kaposi’s sarcoma along with chronic lymphocytic leukemia in a patient who did not receive therapy for chronic lymphocytic leukemia.
The aim of this report is to present a case of a patient with a recurrent nasal cavity amelanotic melanoma (AM), with emphasis on diagnosis and therapy options of this clinical entity. A 65-year-old ...female patient presented with pain in the right cheek region and nasal obstruction. In 2013, she was diagnosed with mucosal melanoma (MM) of the left nasal cavity. After endoscopic surgery and radiotherapy, the patient was followed by the oncology team. Five years after the initial diagnosis, rhinoscopy showed a tumorous formation in the right nasal cavity. The tumor mass was without black discoloration and was the same color as the surrounding nasal mucosa. Microscopic examination after biopsy of the tumor confirmed amelanotic MM. The patient underwent an additional endoscopic surgery. A complete standard diagnostic workup for MM found metastases in head and neck lymph nodes, on both sides. MMs of head and neck are uncommon malignancies. Unique biology of MM cells causes a high rate of recurrences. This report presents an example of recurrent AM of the nasal cavity, in treatment with checkpoint inhibitor (pembrolizumab), which could provide a good therapy option for patients with MM.
Primary angiosarcoma of the breast is a rare tumour that account for fewer than 0.05% of all malignant mammary tumours. Angiosarcoma may have an perfidious clinical onset. Radiologic findings are ...often nonspecific and may appear completely normal in one-third of cases with primary angiosarcoma. The prognosis is usually poor because of the high rates of local recurrence and early development of metastases. Aggressive surgical resection is the mainstay of treatment. The role of adjuvant therapy has not yet been well established. Here we present a case of a 53 year old, postmenopausal women with primary angiosarcoma arising in fibroadenoma. To our knowledge, this is the first case described in the literature to date.
Cilj: Predstaviti slučaj potencijalnog malignog alteriranja lezije blue naevus i skrenuti pozornost na važnost istraživanja ove lezije koja, ako se propusti pravilna dijagnostika i terapija, može ...ostaviti po život opasne posljedice. Prikaz slučaja: Tridesetšestogodišnji muškarac javlja se u ambulantu Klinike za maksilofacijalnu kirurgiju KBC-a Rijeka zbog naglo nastale, bezbolne otekline u preaurikularnoj regiji desno, veličine 3 × 2 cm. Pri pregledu postavljena je sumnja na tumorsku masu u desnoj parotidnoj žlijezdi zbog čega je indicirana citopunkcijska dijagnostika, koja je pokazala kako se radi o metastazi melanoma. Indicirana je, a zatim i učinjena superficijalna parotidektomija zahvaćene žlijezde. Poslijeoperacijski tijek bio je uredan. Patohistološka analiza odstranjene žlijezde potvrdila je dijagnozu metastaze melanoma. Započelo je traganje za primarnim sijelom melanoma, koje nikada nije pronađeno. Iz anamneze se doznalo kako je pacijent ranije iste godine u privatnoj zdravstvenoj ustanovi bio podvrgnut kirurškom zahvatu ekscizije madeža na desnoj strani lica temporalno. Nalaz patohistološke dijagnostike ekscidiranog madeža pokazao je da se radi o benignoj leziji blue naevus. U idućim godinama pacijent je na redovnim kontrolama, pregledima i pretragama raznih specijalista i multidisciplinarnih onkoloških timova. Pacijent je u navedenom razdoblju dobivao učestale metastaze melanoma po cijelom organizmu, zbog čega je podvrgnut više od 20 operativnih zahvata. Posljednji nalazi pokazuju kako su kod pacijenta pronađene dvije metastaze melanoma u mozgu. Zaključci: Iako je lezija blue naevus česta eflorescencija čije je liječenje u većini slučajeva bezazleno, nove spoznaje upućuju na potencijal za malignim alteriranjem ove lezije, na temelju sve većeg i češćeg broja opisanih slučajeva. Potrebno je produbiti istraživanja o ovoj potencijalno opasnoj leziji, sve dok se ne utvrdi kada, na koji način i može li uopće blue naevus maligno alterirati, čime će se dijagnostika i liječenje moći reevalvirati i preciznije izvoditi, što će imati izniman utjecaj na preživljavanje i kvalitetu života pacijenata.
Aim: To present a case of a potentially malignant alteration of a blue naevus lesion and draw attention to the importance of researching this lesion, which, if proper diagnosis and therapy are inadequate and apsent, can have life-threatening consequences. Case report: a thirty-six-year-old male presents himself to the Clinic for Maxillofacial Surgery at the Clinical Hospital Center Rijeka due to a sudden, painless swelling in the right preauricular region, measuring 3×2 cm. During the examination, a tumor mass in the right parotid gland was suspected, which is why cytopuncture diagnostics was indicated, showing that it was a metastasis of melanoma. Superficial parotidectomy of the affected gland was indicated and then performed, with an orderly postoperative course. Pathohistological analysis of the removed gland confirmed the diagnosis of melanoma metastasis. A search began for the primary melanoma site, which was never found. From the anamnesis, it was learned that earlier in the same year, the patient underwent surgical excision of a mole on the right side of the temporal region of the face in a private health institution. The pathohistological diagnosis of the excised mole showed that it was a benign blue naevus lesion. In the following years, the patient had regular controls and examinations by various specialists and multidisciplinary oncology teams. In that period, the patient had frequent melanoma metastases throughout his body, for which he underwent more than 20 surgical procedures. The latest findings show that two melanoma metastases were found in the patient’s brain. Conclusions: Although the blue naevus lesion is a frequent efflorescence, the treatment of which is harmless in most cases, new findings point to the potential for malignant alteration of this lesion, based on the increasingly more frequent number of described cases. It is necessary to deepen the research on this potentially dangerous lesion, until it is determined when, in what way and if at all blue naevus can turn malignant, which will allow diagnostics and treatment to be reevaluated and performed more precisely, which will have an exceptional impact on the survival and quality of patients’ lives.
Background
The spread and invasion of malignant melanoma cells involve degradation and reorganization of the extracellular matrix by the activation of several matrix metalloproteinases (MMPs). This ...study analyzed the expression of MMP‐1, MMP‐2, and MMP‐13 proteins in primary nodular melanoma (NM) and dysplastic nevi (DN) as a significant risk factor for melanoma development. The secondary goal was to analyze the correlation of MMPs protein expression in NM with tumor invasion, BRAF V600 mutation status, and overall survival.
Methods
Immunohistochemistry for MMP‐1, MMP‐2, and MMP‐13 was performed on nodular melanoma (n = 52) and dysplastic nevi (n = 28) on tissue microarray (TMA). BRAF V600 mutation analysis on NM samples was performed by the Sanger sequencing method.
Results
A high level of MMPs expression in NM samples (>30%) compared with DN (<8%) was statistically significant (P < 0.001). BRAF V600 mutations were detected in 15 of 39 (38.5%) NM samples. This study revealed an interesting finding that MMP‐1 and MMP‐13 protein expression in the BRAF V600 mutated melanomas were significantly lower than in the BRAF V600 wild type (P < 0.05).
Conclusion
Cox analysis revealed that Clark categories, Breslow thickness, and MMP‐1 high protein expression are predictive factors for shorter overall survival (P < 0.05).
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