Light chain deposition disease: pathogenesis, clinical characteristics and treatment strategies.

Light chain deposition disease (LCDD) is a rare hematologic disorder characterized by the deposition of non-amyloid monoclonal light chains in several organs. Together with renal impairment is being the primary morbidity associated with this disease. Due to its rarity, randomized clinical trials lack to explore treatment strategies and there are no approved or universally accepted standard of care treatment options. We aimed to provide a systematic summary of histological and clinical aspects of LCDD and treatment options of available literature therapies strategies. Currently, drugs used to treat multiple myeloma are recommended when LCDD patients also presented multiple myeloma. Anyway, in patients with LCDD that is not associated to multiple myeloma, haematopoietic stem cell transplantation (ASCT) and chemotherapy with thalidomide, dexamethasone, bortezomib are also recommended. In eligible patients, bortezomib-based chemotherapy followed by ASCT appears to be an effective treatment option with durable hematologic remission and organ responses. Although it appears that the patients undergoing ASCT seem to achieve deeper and durable hematologic remissions and organ responses, no statistically significant superiority can be demonstrated over non-transplant or standard chemotherapy-based approaches. As retrieved by our review, bortezomib-based therapy appears to be favorable strategy as long as no dose modification is required for renal impairment, and early hematologic responses as a recovery of renal function. Encouraging data were also demonstrated by treatment lenalidomide or melpalan based. Moreover, new myeloma treatment strategies, as monoclonal antibody Daratumumab, seem to be effective in LCDD. Instead, renal allograft is not recommended, due to high incidence of relapse.

Lipoblastoma-Like Tumor and Fibrosarcoma-Like Lipomatous Neoplasm Represent the Same Entity: A Clinicopathologic and Molecular Genetic Study of 23 Cases Occurring in Both Men and Women at Diverse Locations.

Lipoblastoma-like tumor (LLT) is a benign soft tissue tumor demonstrating mixed morphologic features of lipoblastoma, myxoid liposarcoma, and spindle cell lipoma but lacking genetic alterations associated with those tumors. LLT was originally thought to be specific to the vulva but has since been reported in the paratesticular region. The morphologic features of LLT overlap with those of "fibrosarcoma-like lipomatous neoplasm" (FLLN), a rare, indolent adipocytic neoplasm considered by some to form part of the spectrum of atypical spindle cell and pleomorphic lipomatous tumor. We compared the morphologic, immunohistochemical, and genetic features of 23 tumors previously classified as LLT (n = 17) and FLLN (n = 6). The 23 tumors occurred in 13 women and 10 men (mean age, 42 years; range, 17 to 80 years). Eighteen (78%) cases arose in the inguinogenital region, whereas 5 tumors (22%) involved noninguinogenital soft tissue, including the flank (n = 1), shoulder (n = 1), foot (n = 1), forearm (n = 1), and chest wall (n = 1). Microscopically, the tumors were lobulated and septated, with variably collagenized fibromyxoid stroma, prominent thin-walled vessels, scattered univacuolated or bivacuolated lipoblasts, and a minor component of mature adipose tissue. Using immunohistochemistry, 5 tumors (42%) showed complete RB1 loss, with partial loss in 7 cases (58%). RNA sequencing, chromosomal microarray, and DNA next-generation sequencing study results were negative for significant alterations. There were no clinical, morphologic, immunohistochemical, or molecular genetic differences between cases previously classified as LLT or FLLN. Clinical follow-up (11 patients [48%]; range, 2-276 months; mean, 48.2 months) showed all patients were alive without disease, and only one patient had experienced a single local recurrence. We conclude that LLT and FLLN represent the same entity, for which "LLT" seems most appropriate. LLT may occur in either sex and any superficial soft tissue location. Careful morphologic study and appropriate ancillary testing should allow for the distinction of LLT from its potential mimics.

A new technique of ultrasound guided percutaneous renal biopsy by perforated probe and perpendicular needle trajectory.

The percutaneous biopsy of native kidneys according to the classical methodology is performed under real time ultrasound guidance with the needle introduction along a trajectory of about 30°, aimed to the lower pole of the kidney. Recently, a variant of the classical technique has been introduced by which a perforated ultrasound probe is used to guide the needle along a perpendicular trajectory to the terminal section of the lower kidney pole where the front and back margins of the cortical kidney tissue join each other without renal sinus interposition so to offer to the needle a 3-4 cm thick cortical tissue front which allows to obtain a cortical tissue sample suitable for histological examination even with a single needle pass, while at the same time limiting the possibility of damaging the smaller kidney calices of the lower group whose lesion causes hematuria. In this paper, we present a large survey (50 patients) to compare to data from the literature obtained by using similar needle gauge and with a similar follow-up period after biopsy. The result of this comparison confirms the efficacy of this variant of the classical technique because in front of a statistically lower number of needle passes, it allowed to obtain 100% of samples suitable for histological analysis, in absence of major complications and with a statistically lower post-biopsy hemoglobin drop in comparison to that observed in a group of 44 patients biopsied with a greater number of needle passes, in the only study of the literature which is directly comparable to our study in relation to needle gauge and duration of monitoring.

Shedding light on PRAME expression in dysplastic nevi: a cohort study.

Dysplastic nevi represent one of the least agreed-upon entities in dermatopathology despite the existence of established criteria. This study explores preferentially expressed antigen in melanoma (PRAME) in dysplastic nevi, an uncharted area. We examined 22 common melanocytic nevi (CMN), 20 cutaneous melanomas (CM), 48 low-grade dysplastic nevi (LG-DN), and 40 high-grade dysplastic nevi (HG-DN). PRAME was immunohistochemically assessed using a five-tiered system (0 to 4 +). Among CMN, 59% scored 0, 32% scored 1 + , and 9% scored 2 + . CM had score 2 + and 4 + in 11% and 89% of cases, respectively. Among LG-DN, 38% presented score 0, 31% score 1 + , 17% score 2 + , 8% score 3 + , and 6% score 4 + . Thirty per cent of HG-DN demonstrated a score 0, 30% with score 1 + , 15% score 2 + , 10% score 3 + , and 15% score 4 + . Compared to CMN and CM, LG-DN and HG-DN showed heterogeneous expression profiles of PRAME. PRAME positivity effectively distinguished HG-DN from CM with 85% specificity and 80% sensitivity (p < 0.0001). Predictive values were 87% (negative) and 76% (positive). Furthermore, a trend of increased PRAME expression from LG-DN to HG-DN was observed. However, the applicability of PRAME in the differential diagnosis of dysplastic lesions remains unclear as can yield conflicting results with morphology, which remains the primary diagnostic tool for melanocytic lesions.

Bone turnover profile and muscular status in major orthopaedic surgery: a case series.

BACKGROUND Sarcopenia refers to a chronic loss of skeletal muscle mass, often associated with hypovitaminosis D and advanced age, which involves a greater risk of falls and fractures. The association of sarcopenia and osteoporosis defines osteo-sarcopenia. In this work, the authors analyzed the osteometabolic profile and the loco-regional muscular state of patients undergoing major orthopedic surgery, in order to define the incidence of district osteosarcopenic states, linked to a condition of disuse.   METHODS   19 patients (10M-9F), between 15 and 85 years old, underwent major orthopedic surgery (15 resection prosthesis and custom made, 2 resection and reconstruction with transplant) were evaluated, of which 9 on an oncological basis. In all patients, the phospho-calcium metabolism was assessed by blood tests and intraoperative muscle biopsy was performed at the intervention site and contralaterally; in 3 cases a densitometric comparative study of the affected/contralateral limb was performed.   RESULTS   Results shows 5 patients with hypovitaminosis D; 7 pcs with hypocalcemia; 5 with PTH rise; 4pcs with ALP increase. In 100% of cases, the biopsy revealed sarcopenic patterns exclusively on the affected limb. 2 out of 3 DEXAs (66%) showed loco-regional osteoporosis compared to the contralateral.   CONCLUSIONS   The fact that in our sample sarcopenia is unilateral affecting only the pathological limb, that it is frequently associated with osteoporosis which is also unilateral and that for the most part it is not associated with vitamin D deficiency, suggests that it is an independent condition, with etiopathogenetic mechanisms different from osteosarcopenia itself. In major orthopedic surgery, bone integration and muscle status are both essential for achieving and lasting positive results. Considering the high incidence of district osteosarcopenia, an integrated surgical, pharmacological, and rehabilitative approach is desirable for the optimization of results, as well as more studies for the definition of the etiopathogenesis of this pathological condition.

A Multisystem Mitochondrial Disease Caused by a Novel MT-TL1 mtDNA Variant: A Case Report.

BACKGROUND: Mitochondrial tRNA (MTT) genes are hotspot for mitochondrial DNA mutation and are responsible of half mitochondrial disease. MTT mutations are associated with a broad spectrum of phenotype often with complex multisystem involvement and complex genotype-phenotype correlations. MT-TL1 mutations, among which the m.3243A>G mutation is the most frequent, are associated with myopathy, maternal inherited diabetes and deafness, MELAS, cardiomyopathy, and focal segmental glomerulosclerosis. CASE STUDY: Here we report the case of an Italian 49-years old female presenting with encephalomyopathy, chronic proteinuric kidney disease and a new heteroplasmic m.3274_3275delAC MT-TL1 gene mutation. CONCLUSIONS: Our case demonstrates a systemic mitochondrial disease caused by the heteroplasmic m.3274_3275delAC MT-TL1 gene mutation, not yet described in the literature. A mitochondrial disease should be suspected in case of complex multisystem phenotypes, including steroid-resistant nephrotic syndrome with multisystemic involvement.

Renal Involvement in IgG4-Related Disease: From Sunlight to Twilight.

IgG4-Related Disease (IgG4-RD) is a fibroinflammatory condition characterized by a typical histopathological pattern (dense lymphoplasmacytic infiltrate with prevalent IgG4+ plasma cells and storiform fibrosis), which may involve the kidney both directly (IgG4-related kidney disease, IgG4-RKD) or indirectly, as a consequence of post-renal ureteral obstruction due to retroperitoneal fibrosis (IgG4-RD RF). The most frequent presentation of IgG4-RKD is IgG4-related tubulointerstitial nephritis (TIN), but a glomerular disease can be present, in most of the cases a membranous nephropathy. Albeit steroid-responsive, in some cases renal manifestations may lead to progressive and permanent organ damage. In this review we describe four clinical cases representative of typical and less typical renal manifestations of IgG4-RD, emphasizing a potential, subclinical, early involvement of the kidney in the disease.

Pyoderma Gangrenosum: A Current Problem as Much as an Unknown One.

Pyoderma gangrenosum (PG) is a rare neutrophilic inflammatory skin disease, characterized by recurrent skin ulcers, which in almost 50% of cases are associated with systemic autoimmune disorders, including rheumatoid arthritis, chronic hepatitis, inflammatory bowel disease, paraproteinemias and hematological malignancies. A systematic search of literature for PG was carried out using the PubMed, Embase, and Google Scholar databases for the purpose of this review and 2780 articles were retrieved up to February 2017. Inflammation represents the predominant aspect of the disease, but its pathophysiological mechanisms are not completely clear yet, since there are many studies showing only one or more isolated findings of the disease. The goal of PG treatment is to reduce inflammation in order to promote ulcer healing by minimizing side effects of therapy. Several systemic and local treatments are available, but the lack of large randomized double-blind studies results in an absence of a uniform therapeutic standard: thus, more clinical studies are required in order to make head-to-head comparisons between combination and single-drug therapies and to identify specific combination therapies for distinctive clinical patterns of PG.

[A variant of the classic technique of ultrasound guided percutaneous renal biopsy: the perpendicular entry by longitudinal viewing planes with a perforated probe].

The percutaneous biopsy of native kidneys according to the classic methodology, takes place with the introduction of the needle and its guide with ultrasound sagittal viewing planes, with a 30-degree angle, up to the lower pole of the kidney. Since the longitudinal axis of the kidneys converges towards the spine with a sharp angle, we observed that starting from a longitudinal scan of the kidney (conducted along the posterior axillary line with the patient prone) you can drive the needle by a perforated probe through a shorter path perpendicular to the end section of the lower pole of the kidney where the front and rear rims of the cortex bearings without the renal sinus interposed so increasing the chance to obtain, even with a single pass, a good sample of cortical tissue while limiting the possibility to damage the lower chalices that may cause hematuria. We biopsied in that manner 26 patients and we compared the data with those reported in the literature performed with the same needle gauge and post-biopsy monitoring period. With a statistically lower number of needle passes, it is thus obtained the 100% of the sample validity for histological analysis, in absence of major complications and statistically hemoglobin variance when compared with a group of 44 patients biopsied with a significantly greater number of needle passes in the only work carried out with classical technique in the literature (Ori et al.) which is directly comparable to our for gauge of the needles and duration of monitoring.