Recognizing calcific uremic arteriolopathy in autoimmune disease: an emerging mimicker of vasculitis

Calcinosis has long been associated with autoimmune disease and has a distinctive profile in scleroderma, dermatomyositis, systemic lupus erythematosus, and overlap syndromes. However, there have also been a number of case studies of calcific uremic arteriolopathy, or calciphylaxis, described within vessels, including patients with chronic renal insufficiency and several forms of vasculitis. Interestingly, the calciphylaxis associated with vasculitis appears to be unique, although relatively uncommon and is likely secondary to a disruption in the calcium-phosphate-parathyroid hormone axis. However, there appears to be an additional trigger, given that calciphylaxis is seen both in the absence of chronic kidney disease, and in the absence of a deranged calcium-phosphate-parathyroid hormone axis. These additional triggers include a high female predominance, obesity, diabetes and, possibly, warfarin use. In this review, we describe the clinical features of calciphylaxis, particularly in the context of autoimmune disease.     

The development of the pathophysiological concept of calciphylaxis in experiment and clinic

An attempt to clarify some pathophysiological aspects of calciphylaxis from both experimental and clinical points of view is presented. Until now, we cannot explain precisely various forms of calcification, affecting either soft tissues or biomaterial as well, only on the basis of metastatic or dystrophic calcification including the pure topical, local aspects. Therefore, the biological phenomenon of calciphylaxis can be useful in searching the ways for the inhibition of soft tissues and biomaterial calcification. The experiments with experimental progeria have also made it possible to study the so-called reversed calciphylaxis. The systemic reversed calciphylaxis, or ‘anacalciphylaxis’ was shown in the authors experiments with the total artificial heart as a very effective factor in the inhibition of mineralization of the TAH driving diaphragms. The discovery of the ubiquitous organ regulator of calcification, osteopontin, can greatly contribute to further elucidation of the calciphylactic mechanisms in general, and also to the prevention of calcifying lesions. It is pointed to some clinical states, predominantly the end-stage renal disease with hemodialysation where many authors pay attention to calciphylaxis as a clinical entity in a series of such cases. Calciphylaxis has been described in dermatology, nephrology and other clinical disciplines. In the area of attempts to prevent the ectopic organ calcification and also mineralization of biomaterials, a vast field of stimulation of endogenic inhibitors of calcification remains open.     

Calciphylaxis cutis: A case report and review of literature

Calciphylaxis is a poorly understood syndrome of vascular calcification and skin necrosis. It affects 1-4% of the population with end stage renal disease (ESRD). Disorders implicated in the pathogenesis of calciphylaxis include chronic renal failure, hypercalcemia, hyperphosphatemia, an elevated calcium-phosphate product, and secondary hyperparathyroidism (Essary, L.R. and Wick, M.R. (2000) Cutaneous calciphylaxis. An underrecognized clinicopathologic entity. Am. J. Clin. Pathol. 113, 280-287, Beitz, J.M. (2004) Calciphylaxis: an uncommon but potentially deadly form of skin necrosis. Am. J. Nurs. 104, 36-37.). Although these abnormalities are extremely common in-patients with ESRD, calciphylaxis is relatively rare. The mortality rate of calciphylaxis is about 60-80%. The leading cause of death is sepsis from necrotic skin lesions (Hitti, W.A., Papadimitriou, J.C., Bartlett, S. and Wali, R.K. (2007) Spontaneous cutaneous ulcers in a patient with a moderate degree of chronic kidney disease: a different spectrum of calciphylaxis. Scand. J. Urol. Nephrol. 1-3.). Here, we report a case of calciphylaxis in a 23-year-old female with past history of chronic renal failure, renal transplantation and intake of immunosuppressive drug. The relevant literature was discussed.     

An unusual presentation of calciphylaxis due to primary hyperparathyroidism

We present the case of a 69-year-old woman with calciphylaxis due to primary hyperparathyroidism. A 0.5-g parathyroid adenoma was surgically removed, which resulted in complete recovery of the patient. Review of the literature revealed 7 other cases of calciphylaxis due to primary hyperparathyroidism and showed that prompt surgical removal of the autonomous parathyroid gland lesion results in clinical recovery of calciphylactic skin lesions.     

Combination of sodium thiosulphate, cinacalcet, and paricalcitol in the treatment of calciphylaxis with hyperparathyroidism

Calciphylaxis (calcific uremic arteriolopathy) is a severe complication of hemodialysis characterized by subcutaneous calcification of the small arteries and tissue necrosis. Our case report is focused on a woman receiving hemodialysis (HD) with diabetes mellitus for 20 years and severe secondary hyperparathyroidism, who presented painful subcutaneous nodules, skin necrosis and ulcerations. As the treatment of calciphylaxis is mainly empirical and controversial, we decided to administer cinacalcet with paricalcitol for the control of hyperparathyroidism and sodium thiosulfate to improve the calcification of the arterioles. Two months after the start of the therapy, parathyroid hormone (PTH) decreased significantly and the skin lesions nearly disappeared. Thus, we believe that the combination of sodium thiosulfate with cinacalcet and paracalcitol is effective for the treatment of calciphylaxis with secondary hyperparathyroidism.     

Amyloid goiter--a case report

Microscopic infiltration of the thyroid gland by amyloid is an uncommon but well recognized phenomenon and significant enlargement of the thyroid due to deposition of amyloid is rarely seen. This condition has to be distinguished from other types of goiters and at times from malignancy. In spite of extensive involvement of the gland by amyloid, thyroid function usually remains normal. Here, we describe a rare case of amyloid goiter without amyloid deposits in any other organs of the body. The case presented in an unusual clinical settings of relatively rapid enlargement of thyroid with pressure symptoms and was unassociated with any immuno-proliferative or chronic diseases.     

Cherubism--a case report with long term follow up

Cherubism is a rare non-neoplastic disease of the bone characterized by bilateral painless enlargement of the jaws giving a cherubic appearance to the patient. It is an autosomal dominant disorder but may occur sporadically. In this paper, we have tried to explain about the clinical, radiological and histopathologic features of cherubism by presenting a case study. A case study of a 7 year old male patient, who first presented with mandibular bilateral swellings to our department in 1998, has been presented. In-depth clinical, radiological and histopathologic examination was done. An extensive long-term follow-up till 11 years was maintained. When presented for the first time, radiological investigation showed characteristic multilocular lytic lesions of the mandible bilaterally. Histopathological examination of the biopsy specimen showed proliferating fibrous connective tissue interspersed by multinucleated giant cells. It was diagnosed as a case nonfamilial cherubism. Follow-up after 5 years showed involvement of the maxilla as well, which was then corrected by surgical methods. Upon follow up 11 years after the first presentation, it was seen that the lesion was regressing by itself and there was improvement in facial contour. The natural course of Cherubism through its progression, stabilization and involution of the disease after puberty, has been highlighted in this case. More, in-depth studies to understand the nature and the pathogenesis of this condition better are required.     

Calciphylaxis involving both the upper and lower extremities

Calciphylaxis is an uncommon complication of end stage renal disease (ESRD) and secondary hyperparathyroidism. It characterized by cutaneous necrosis with mural calcifications and thrombosis in the small vessels of dermis. It is important to diagnose and treat, because of mortality rate from calciphylaxis is very high. We present the case of a patient with ESRD and type II diabetes mellitus developing calciphylaxis of the both upper and lower extremities had normal corrected calcium-phosphate product level. After amputation, necrosis was showed rapid progression resulting in death in one month.     

Case report: amyloid tumors in a case of non-secretory multiple myeloma

Multiple myeloma (MM) is a neoplastic disorder characterized by proliferation of a single clone of plasma cells derived from B cells, which proliferates in the bone marrow and frequently invades the adjacent bone, producing skeletal destruction that results in bone pain and fractures. Patients with MM can furthermore present with anemia, hypercalcemia and renal failure. Non-secretory multiple myeloma (NSMM) is characterized by the absence of a monoclonal (M) protein in both the serum and urine. The reported incidence is 1-5% of all multiple myeloma cases. Development of amyloid tumors in NSMM has been described in the literature only occasionally. The clinical features of a 49-year-old female patient with NSMM and amyloid tumors in the breast, lung and rib are presented in this report. Conventional histology, Congo red staining with and without potassium permanganate pretreatment, aldehyde bisulfite-toluidine blue (ABT) reaction, sialic acid specific topo-optical reaction, toluidine blue topo-optical reaction as well as immunohistochemistry were performed. An attempt is made to explain the lack of monoclonal immunoglobulins in the serum and urine, although extensive organ amyloidosis of AL type (kappa-light chains) has been found. It is assumed that the plasmocytic plasma cells possess an excretory mechanism, which allows the pathologic immunoglobulins to be secreted either as amyloid proteins polymerizing into amyloid fibrils, or as immunoglobulin fragments that are subject to degradation as soon as they are excreted out of the tumor cell. In this paper, we review the occurrence of amyloid tumors in non-secretory multiple myeloma and, in a single case report, we confirm the existence of carbohydrate residues, including sialic acids and sulfated GAGs, in amyloid deposits.     

A case of pulmonary capillary hemangiomatosis with pulmonary fibrosis associated with MMP-9 related pulmonary remodeling

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension. It is characterized capillary proliferation within the alveolar septa. Here, we report a case of PCH with extensive pulmonary fibrosis. A 52-year-old man with a clinical diagnosis of non-specific interstitial pneumonia died of respiratory failure with severe pulmonary hypertension. Autopsy revealed pronounced right ventricle hypertrophy and pulmonary fibrosis. Consistent with clinical diagnosis, histological examination revealed diffuse pulmonary fibrosis, in addition, it also disclosed marked capillary proliferation within the alveolar septa as well as the fibrotic pulmonary stroma, suggesting the presence of PCH. Hemosiderin-laden macrophages had accumulated in the capillary proliferative area, and bronchiolar-type metaplasia was conspicuous in the fibrotic lesion. Proliferated capillaries were surrounded by fine collagen and α-smooth muscle actin-positive myofibroblasts. Immunohistochemistry revealed that type IV collagen around capillaries in the area of the PCH without inflammation disappeared in the area with inflammation. In addition, the PCH lesion contained significant numbers of macrophages expressing matrix metalloproteinase (MMP) 9 and type II pneumocytes positive for vascular endothelial growth factor. Although pulmonary fibrosis is a distinctive disease entity, different from PCH, MMP-9-driven destruction of the basement membrane may promote unusual pulmonary remodeling, which, in this case, resulted in extensive pulmonary fibrosis.     

Ichthyosis uteri: a case report and review of the literature

Squamous metaplasia of endometrium is mostly manifested by morules or nodules of benign nonkeratinizing squamous cells intimately mixed with benign or malignant endometrial glands. It has been described with low-grade adenocarcinoma of the endometrium, as well as with various benign conditions, including hyperplasia, chronic endometritis, and endometrial polyps. However, extensive plaquelike, keratinizing squamous change is distinctly uncommon. To our knowledge, we describe the first case of extensive benign squamous keratinization with underlying endometrial adenocarcinoma.     

Hyalinoid giant cell gastritis. A unique gastric lesion associated with eosinophilic hyalinoid degeneration of smooth muscle

A rare case of degenerative and inflammatory lesion of the stomach occurring in a 34-year-old woman is reported. Clinically, the lesion simulated gastric carcinoma because of the extensive involvement of the mucosa and submucosa by the process. Histologically, it was characterized by eosinophilic hyalinoid degeneration of smooth muscles in the muscularis mucosae as well as mucosal and submucosal blood vessels accompanied with foreign body giant cells and other inflammatory cells. The lesion occurred in association with chronic peptic ulcers, and a small submucosal nodule histologically compatible with inflammatory fibroid polyp coexisted within the area of this lesion. The patient has had no systemic disease and has been well for 4.5 years postoperatively. These clinical features suggest a localized nature of the lesion limited to the stomach. The term "hyalinoid giant cell gastritis" is proposed to describe this distinctive form of gastritis.     

Autoimmunity in 2017

The number of peer-reviewed articles published during the 2017 solar year and retrieved using the “autoimmunity” key word increased significantly compared to 2016 while maintaining a stable share within the immunology field, following years with alternated fortunes. A detailed arbitrary analysis of the published articles in leading immunology and autoimmunity journals provides a privileged viewpoint on the current trends of research from both basic and clinical studies. Indeed, we are observing that major steps forward are found for rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, among others. In particular, the new data on pregnancy success in lupus or biomarkers in systemic sclerosis are believed to change our management of these systemic conditions. In the case of rheumatoid arthritis, we have obtained data with significant implications in the understanding of the disease pathogenesis (as in the case of platelets), disease phenotyping, and new treatment options. Furthermore, the exponential growth of treatment options for cancer based on immune checkpoint modulation is paralleled by the need to address the potential autoimmunity side effects while taking advantage of new information obtained in paraneoplastic autoimmune conditions. Cumulatively, 2017 has been a very exciting year for autoimmune diseases, and we foresee that most of the data discussed herein will be followed by more extensive studies in the upcoming months.     

Basal cell adenoma with extensive squamous metaplasia and cellular atypia: a case report with cytohistopathological correlation and review of the literature

Basal cell adenoma (BCA) is a rare benign basaloid neoplasm of the salivary gland. There are four histopathological types of BCA: solid, tubular, trabecular, and membranous. It is known that focal squamous metaplasia may be seen in some BCAs, but it is rare to see extensive squamous metaplasia, especially with cellular atypia. Here, a 25-year-old male with right parotid swelling is presented. Ultrasonography revealed a 2-cm well defined mass in his parotid gland. Fine-needle aspiration (FNA), performed prior to surgical excision, showed a highly cellular tumor composed of basaloid cells, forming small duct-like or tubular structures containing basement membrane-like material, as well as squamous cells with hyperchromatic, enlarged, pleomorphic, and bizzare nuclei. We made a cytopathological diagnosis of "basaloid neoplasm" and also reported that the differential diagnosis included BCA, cellular pleomorphic adenoma, basal cell adenocarcinoma, and carcinoma ex pleomorphic adenoma. The patient underwent total parotidectomy. Both frozen and permanent sections showed a BCA with membranous, tubulotrabecular pattern, and extensive squamous metaplasia. Some of the squamous cells showed significant nuclear hyperchromasia, enlargement, and pleomorphism. As far as we know, this is the first case of BCA with extensive squamous metaplasia and prominent cellular atypia. This case has been presented to show that squamous metaplastic cells with hyperchromatic, enlarged, bizarre, and pleomorphic nuclei can be seen on FNA smears of a benign tumor like BCA. Also, the differential diagnosis of BCA of the salivary gland is discussed here.     

Metastatic medullary thyroid carcinoma or calcitonin‐secreting carcinoid tumor of lung? A diagnostic dilemma in a patient with lung mass and thyroid nodule

Calcitonin‐secreting neuroendocrine tumors are rare and have been reported in literature as case reports or case series in various organs including lung, pancreas, larynx, bladder, and ovary. These tumors have similar cytologic features and immunohistochemical profile to medullary thyroid carcinoma and thus it is difficult to distinguish them, especially when calcitonin‐secreting neuroendocrine tumors are intermediate or higher grade and there is a mass lesion in the thyroid gland. Here, we report a rare case of calcitonin secreting atypical carcinoid tumor of the lung in a patient with thyroid nodule. However, after extensive ancillary studies on the thyroid gland, no tumor was detected and subsequent resection specimen revealed a pulmonary atypical carcinoid tumor with metastasis to level 11 lymph node. Being aware of this entity has significant clinical, diagnostic, and therapeutic implications and can prevent unnecessary thyroidectomies with subsequent possible morbidities.     

Antimicrobial photodynamic therapy – what we know and what we don’t

Considering increasing number of pathogens resistant towards commonly used antibiotics as well as antiseptics, there is a pressing need for antimicrobial approaches that are capable of inactivating pathogens efficiently without the risk of inducing resistances. In this regard, an alternative approach is the antimicrobial photodynamic therapy (aPDT). The antimicrobial effect of aPDT is based on the principle that visible light activates a per se non-toxic molecule, the so-called photosensitizer (PS), resulting in generation of reactive oxygen species that kill bacteria unselectively via an oxidative burst. During the last 10–20 years, there has been extensive in vitro research on novel PS as well as light sources, which is now to be translated into clinics. In this review, we aim to provide an overview about the history of aPDT, its fundamental photochemical and photophysical mechanisms as well as photosensitizers and light sources that are currently applied for aPDT in vitro. Furthermore, the potential of resistances towards aPDT is extensively discussed and implications for proper comparison of in vitro studies regarding aPDT as well as for potential application fields in clinical practice are given. Overall, this review shall provide an outlook on future research directions needed for successful translation of promising in vitro results in aPDT towards clinical practice.     

Ipsilateral breast metastasis from a pulmonary adenocarcinoma: a case report and a focused review of the literature

Metastases to the breast from extramammary malignancies are extremely rare. Ruling out the diagnosis of primary breast tumor is important in order to decide on clinical management and predict prognosis. We report a case of metastasis to the breast from a pulmonary adenocarcinoma, with extensive micropapillary component, diagnosed concomitantly with the primary tumor. A 52 year-old female patient presented with mammary gland tingling and dyspnea accompanied with fatigued of 4 months duration and a nodular shadows in the front of the upper lobe was found on a chest computed tomography (CT) scan. The original clinical diagnosis was right breast cancer with lung and bone metastasis, or breast and lung double primary cancers. In addition,on physical examination a poorly defined mass was noted in the upper outer quadrant of the right breast. The patient underwent thoracocentesis and breast biopsy. By imageology, cytology, histology and immunohistochemistry, we diagnosed primary lung cancer with metastases to the right breast and bone. The metastatic anatomic sites demonstrated histologically extensive micropapillary component, which is recently recognized as an important prognostic factor. The patient was administered 4 cycles of cisplatin and docetaxel, although no clinical response was seen, the patient is still alive 9 months after diagnosis. The result of immunohistochemistry is a useful supplement in differential diagnosis.     

Malignant glomus tumor of kidney: the first reported case and review of literature

Glomus tumors are mesenchymal neoplasms and are rarely seen in visceral organs like the kidney. Our patient presented with a metastatic, malignant, and highly aggressive glomus tumor in the kidney. In our extensive literature review, we did not come across even a single case of malignant glomus tumor arising in the kidney. We report the clinical presentation, radiologic, and pathological features of our case. Immunohistochemical findings that distinguish our case from other reported cases of glomus tumors arising from the kidney have been discussed. We have also reviewed the criteria for malignancy and other reported malignant glomus tumors.