Sinonasal Adenocarcinoma: Clinicopathological Characterization and Prognostic Factors.

Sinonasal (SN) malignancies are rare. Within SN adenocarcinomas, the most frequent are intestinal-type adenocarcinomas (ITACs). ITAC has been associated with wood and leather dust occupational exposure and TP53 mutations. Not much information is available regarding its characterization and treatment. The aim of this study is to characterize the clinicopathologic and prognostic factors of patients with sinonasal adenocarcinomas (SNACs) treated in our tertiary-level hospital. A retrospective, consecutive study including SNAC patients diagnosed between 2004-2023 was conducted. Clinicopathological data was collected, and p53 status was assessed in the tumor specimens. The association between p53 status and clinicopathological variables, as well as their impact on survival, was evaluated. In total, 35 were included, most of them having ITAC (91.4%) with papillary subtype (37.5%); the majority were subjected to occupational risk exposure (82.9%). Overexpression of p53 was identified in 48.6% of the tumors. Papillary and colonic subtypes were associated with higher median progression-free survival (mPFS) than mucinous and solid subtypes (mPFS 37 months, 95% CI, 20.0-54.0, vs. 9 months, 95% CI, 7.15-10.85, p=0.01); the former was also associated with higher median overall survival (mOS) (mOS 64 months, 95% CI, 37.18-90.81 vs. 14 months, 95% CI, 0-41.58, p=0.02). Histologic grade 1-2 and macroscopic complete resection were associated with higher PFS (PFS of five months of 90.9% vs. 33.3%, p=0.01; mPFS of 37 months, 95% CI, 4.93-69.07 vs. 10 months, 95% CI, 6.43-13.57, p=0.04, respectively). Disease recurrence with distant metastases was associated with lower OS (11 months, 95% CI, 6.1-15.9 vs. 53 months, 95% CI, 22.70-83.30, p=0.04). This study reinforces the importance of protective occupational measures. Future studies will be important to validate the best treatment strategy in the advanced stages of this disease and also to identify new prognostic and/or therapeutic target biomarkers in SNAC.

Lessons from Four Decades of Systemic Amyloidosis with Renal Involvement.

BACKGROUND: Apart from ATTR amyloidosis, the epidemiology and outcomes of the most common subtypes of systemic amyloidosis in Portugal remain primarily unknown. METHODS: This retrospective cohort study evaluated patients with renal biopsy-proven amyloidosis, diagnosed from January 1978 to December 2019. Follow-up started at kidney disease presentation and ended at death or August 2020. Clinical presentation, survival, and prognostic factors were analysed. RESULTS: Of 123 patients with amyloid nephropathy, 111 had definite amyloid typing and were analysed. AA amyloidosis was the most frequent type (56.1%) and was related mainly to chronic infection (47.8%) and chronic inflammatory arthritis (29.0%). AL amyloidosis was present in 25.2% of patients and hereditary forms in 6.5% (4.1% AFibE526V, 2.4% ATTRV30M). During follow-up, 73.9% of AA and 54.8% of AL patients progressed to end-stage renal disease, and 79.7% of AA and 77.4% of AL died; median overall survival was 66.0 (95% CI, 33.0-99.0) and 18.0 (95% CI, 9.3-26.7) months (p = 0.025), respectively. There were no significant differences in renal outcome and survival on dialysis between these two types. In multivariate analysis, cardiac involvement at presentation (HR 6.26 [95% CI, 2.89-13.56]) and estimated glomerular filtration rate <30 mL/min/1.73 m2 (HR 2.05 [95% CI, 1.06-3.99]) independently influenced AA and AL amyloidosis survival. Cardiac involvement at presentation was an independent predictor of death (HR 9.65 [95% CI, 2.91-31.95]) and early mortality in AL amyloidosis. CONCLUSIONS: In Portugal, AA amyloidosis and related chronic infections are still relevant. Regarding AL amyloidosis, the low incidence and advanced disease at presentation result from missed and erroneous diagnoses, leading to delayed referrals and poor outcomes in these patients.

Review of 175 Cases of Tuberculosis Infections Affecting the Urogenital System.

OBJECTIVE: Urogenital tuberculosis and disseminated tuberculosis affecting urogenital system are more fre quent in developing countries but are often overlooked in developed ones. We aimed to compare clinical characteristics and outcomes of urogenital tuberculosis and disseminated tuberculosis affecting the urogeni tal system. MATERIAL AND METHODS: We retrospectively reviewed data from patients with tuberculosis in the urogenital system, diagnosed in a tertiary center in a European country, from 2008 to 2018. Cases were divided into urogenital tuberculosis and disseminated tuberculosis affecting the urogenital system and compared. RESULTS: We included 172 patients, 31 with urogenital tuberculosis and 141 with disseminated tuberculosis affecting urogenital system. Patients with disseminated tuberculosis affecting the urogenital system were younger (median 45 vs. 64 years, P=.001), more likely to be male (80 vs. 55%, P=.005), or having risk fac tors for the disease (84 vs. 23%, P=.005) than patients with urogenital tuberculosis. Patients with urogenital tuberculosis presented most commonly with symptoms related to the urinary tract, with 52% complaining of lower urinary tract symptoms attributed to urinary tract infections and 48% of dysuria, while patients with disseminated tuberculosis affecting the urogenital system presented mainly with systemic symptoms, with 89% complaining of malaise, 62% of fever, and 57% of anorexia. Patients with urogenital tuberculosis were more likely to need urological surgery as part of their treatment (71 vs. 5%, P < .001) and patients with dis seminated tuberculosis affecting the urogenital system were more likely to die due to tuberculosis (10 vs. 21%, P < .001). CONCLUSION: Tuberculosis of the urogenital system can have multiple clinical presentations, and a simple diagnostic algorithm does not exist. In the presence of urogenital tuberculosis in injected drug users, immu nosuppressed individuals, or patients with systemic symptoms, we should think of disseminated tuberculosis affecting the urogenital system and remember these patients less frequently need surgery but entail a worst outcome.

Cardiac Amyloidosis Associated with Apolipoprotein A-IV Deposition Diagnosed by Mass Spectrometry-Based Proteomic Analysis.

Amyloidosis is a group of disorders characterised by the accumulation of extracellular deposits of insoluble protein aggregates. Clinical management depends on the accurate identification of the amyloid precursor and underlying cause. We describe a rare case of apolipoprotein A-IV cardiac amyloidosis, the diagnosis of which required mass spectrometry-based proteomic analysis. LEARNING POINTS: To be able to perform the differential diagnosis of cardiac amyloidosis subtypes using imaging methods, analytical results and tissue analysis.To recognise the added value of mass spectrometry (MS)-based proteomic analysis.

Azathioprine-induced interstitial nephritis in an anti-neutrophil cytoplasmic antibody (ANCA) myeloperoxidase (MPO) vasculitis patient.

Azathioprine (AZA) is used in a wide array of autoimmune diseases, still corresponding to the mainstay maintenance therapy in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Although generally well-tolerated, several side effects are recognized. We report the case of a 50-year-old Caucasian man with kidney-limited ANCA myeloperoxidase (MPO) vasculitis who presented with general malaise, fever, worsening renal function, and elevated inflammatory markers 2 weeks after the initiation of therapy with oral AZA. Although a disease relapse was suspected, renal biopsy revealed an eosinophilic infiltrate, suggestive of acute interstitial nephritis. After suspension of AZA, a sustained improvement of renal function and normalization of inflammatory markers was observed. A diagnosis of allergic interstitial nephritis secondary to AZA was established, corresponding to the first biopsy-proven case described in an ANCA MPO vasculitis patient. Although rare, renal toxicity of AZA must be present in the clinician's mind, avoiding the straightforward assumption of disease relapse in the case of worsening renal function.

Multinodular Goiter Progression Toward Malignancy in a Case of DICER1 Syndrome: Histologic and Molecular Alterations.

OBJECTIVES: Multinodular goiter (MNG) and well-differentiated thyroid carcinoma (WDTC) are emerging phenotypes of DICER1 syndrome. METHODS: Histologic and molecular findings of botryoid-type embryonal rhabdomyosarcoma (bERMS) and thyroid nodules from a 12-year-old DICER1 mutation carrier (p.Arg1060Ilefs*7) were investigated, providing interesting clues for understanding thyroid carcinogenesis. RESULTS: The patient had bERMS at age 7 years. The thyroid was enlarged and multinodular (61 g). Histologically, some nodules were classified as adenomatous and others as tumors with "intermediate" nuclei. One displayed vascular invasion and was classified as WDTC not otherwise specified (NOS). Somatic DICER1 mutations were identified in bERMS, two tumors with "intermediate" nuclei and WDTC. No somatic DICER1 mutations were found in adenomatous nodules. No molecular alterations were detected in BRAF600, NRAS61, HRAS12/61, KRAS12/61, TERT promoter, RET/PTC1, RET/PTC3, and PAX8/PPARγ. CONCLUSIONS: The findings obtained from this single case support the assumption that DICER1 syndrome-related WDTC NOS may develop on a background of MNG, via a stepwise process, involving DICER1 somatic mutations and additional molecular events, distinct from the classic pathways of papillary/follicular carcinoma.

Pigmented lesion of the nipple - a clinicopathological challenge.

Differential diagnoses of pigmented lesions of the nipple include melanocytic nevus, melanosis of the nipple, seborrheic keratosis, pigmented basal cell carcinoma, melanoma and Paget disease. The histologic exam with appropriate immunohistochemistry is a fundamental tool to achieve a correct diagnosis. We present a patient with a pigmented lesion of her right nipple revealing mammary Paget disease and elucidate diagnostic obstacles and prognostic importance of early breast cancer detection.

Morphometric study (macroscopic and microscopic) of the lower abdominal wall.

BACKGROUND: Abdominoplasty using a more superficial plane of dissection has several advantages. Previous studies described a trilaminar structure (superficial and deep fat compartments separated by the Scarpa fascia) in the lower abdominal wall. This study aimed to gain a clearer understanding of compartment dominance and changes with increasing adiposity. METHODS: The study was performed on the surgical specimens of 41 female patients submitted to a full abdominoplasty. A morphometric study was performed on 82 sides to evaluate the thickness of the fat layers at predetermined locations (point A over the external oblique muscle and point B over the rectus abdominis muscle). A histologic study was performed in 31 samples to analyze the structure of the fat compartments and Scarpa fascia. RESULTS: A trilaminar structure was always present, and the Scarpa fascia did not become vestigial with increasing adiposity. Total thickness at point B was significantly higher than that at point A; this difference was mainly attributable to the superficial compartment. The deep fat compartment was always thinner than the superficial, corresponding to 25 percent of total thickness in point A and 23 percent in point B. It was less susceptible to an increase in thickness in cases of obesity. Histologic analysis demonstrated constant morphology, with an average Scarpa fascia thickness of 0.29 mm (point A) and 0.28 mm (point B). CONCLUSIONS: This study demonstrates a trilaminar structure with superficial compartment dominance and Scarpa fascia presence irrespective of adiposity in the lower abdominal wall. The deep fat compartment has a minor contribution to the lower abdominal wall thickness.

Large myocardial infarction with myocardium calcium deposits associated with reperfusion injury.

The clinical and autopsy findings of a 66-year-old man with myocardial infarction complicated by reperfusion injury are described, highlighting the presence of large myocardium calcium deposits.

The "PIP problem": clinical and histologic characteristics.

Implants from Poly Implant Prothése (PIP), the French manufacturer, showed increased risk of implant rupture and silicone leakage through the shell. Concerns also exist about the potential irritant behavior of silicone gel filler in these implants. This report presents the clinical, histologic, and microbiologic characteristics of a capsule and a siliconoma from a patient with a ruptured PIP implant. A 41-year-old woman submitted to breast augmentation in 2005 with PIP silicone gel implants presented with a recent history of progressive asymmetric breast enlargement and an enlarged lymph node on her right axilla. No capsular contracture was observed. A breast ultrasonography showed intra- and extracapsular ruptures of the right implant. The woman underwent explantation. Histologic analysis of the breast capsules showed a thin capsule with a chronic, mild inflammatory response. Microbiologic analysis showed no bacterial agent. The irritant behavior of the PIP silicone gel previously described was not able to produce capsular contracture or an exuberant inflammatory reaction. Studies to evaluate the potential risks of the silicone gel and to define the hazards for women implanted with those prostheses are urgently needed.

Churg-Strauss syndrome presenting with eosinophilic myocarditis: a diagnostic challenge.

Churg-Strauss syndrome (CSS) is an unusual disease that presents as systemic vasculitis and peripheral eosinophilia in patients with an atopic constitution. Cardiac involvement is unusual and often not prominent on initial presentation, but is an important cause of morbidity and mortality in patients with CSS. We report the case of a young woman with severe acute myocarditis. Coronary arteriography demonstrated extensive focal vasculopathy, consistent with coronary vasculitis, and myocardial biopsy showed eosinophilic myocarditis. This presentation led to an initial diagnosis of CSS in this patient and appropriate therapy resulted in a spectacular remission of disease activity.

The impact of triamcinolone acetonide in early breast capsule formation in a rabbit model.

BACKGROUND: The etiology and clinical treatment of capsular contracture remain unresolved as the causes may be multifactorial. Triamcinolone acetonide applied in the pocket during surgery was reported to be ineffective in prevention of capsular contracture. However, if injected 4-6 weeks after surgery or as a treatment for capsular contracture, decreased applanation tonometry measurements and pain were observed. It was assumed that intraoperative application of triamcinolone was not effective because its effect does not last long enough. However, betadine, antibiotics, and fibrin were found to be effective in preventing capsular contracture with intraoperative applications and are more effective in the early phases of wound healing than in later stages. The role of triamcinolone acetonide in capsule formation is unknown. The purpose of this study was to determine if triamcinolone acetonide modulates breast capsule formation or capsular contracture in the early phases of wound healing in a rabbit model. METHODS: Rabbits (n=19) were implanted with one tissue expander and two breast implants and were killed at 4 weeks. Implant pocket groups were (1) Control (n=10) and (2) Triamcinolone (n=9). Pressure/volume curves and histological, immunological, and microbiological evaluations were performed. Operating room air samples and contact skin samples were collected for microbiological evaluation. RESULTS: In the triamcinolone group, a decreased capsular thickness, mild and mononuclear inflammation, and negative or mild angiogenesis were observed. There were no significant differences in intracapsular pressure, fusiform cell density, connective tissue, organization of collagen fibers, and microbiological results between the groups. There was no significant difference in the dialysate levels of IL-8 and TNF-α, but correlation between IL-8 and TNF-α was observed. CONCLUSION: Triamcinolone acetonide during breast implantation influences early capsule formation and may reduce capsular contracture. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

Animal model of implant capsular contracture: effects of chitosan.

BACKGROUND: The mechanism(s) responsible for breast capsular contracture (CC) remain unknown, but inflammatory pathways play a role. Various molecules have been attached to implant shells in the hope of modifying or preventing CC. The intrinsic antibacterial and antifungal activities of chitosan and related oligochitosan molecules lend themselves well to the study of the infectious hypothesis; chitosan's ability to bind to growth factors, its hemostatic action, and its ability to activate macrophages, cause cytokine stimulation, and increase the production of transforming growth factor (TGF)-ß1 allow study of the hypertrophic scar hypothesis. OBJECTIVE: The authors perform a comprehensive evaluation, in a rabbit model, of the relationship between CC and histological, microbiological, and immunological characteristics in the presence of a chitooligosaccharide (COS) mixture and a low molecular weight chitosan (LMWC). METHODS: Eleven adult New Zealand rabbits were each implanted with three silicone implants: a control implant, one impregnated with COS, and one impregnated with LMWC. At four-week sacrifice, microdialysates were obtained in the capsule-implant interfaces for tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) level assessment. Histological and microbiological analyses were performed. RESULTS: Baker grade III/IV contractures were observed in the LMWC group, with thick capsules, dense connective tissue, and decreased IL-8 levels (p < .05) compared to control and COS groups. Capsule tissue bacterial types and microdialysate TNF-α levels were similar among all groups. CONCLUSIONS: Chitosan-associated silicone implantation in a rabbit model resulted in Baker grade III/IV CC. This preclinical study may provide a model to test various mechanistic hypotheses of breast capsule formation and subsequent CC.

Effects of coagulase-negative staphylococci and fibrin on breast capsule formation in a rabbit model.

BACKGROUND: The etiology and ideal clinical treatment of capsular contracture (CC) remain unresolved. Bacteria, especially coagulase-negative staphylococci, have been previously shown to accelerate the onset of CC. The role of fibrin in capsule formation has also been controversial. OBJECTIVE: The authors investigate whether fibrin and coagulase-negative staphylococci (CoNS) modulate the histological, microbiological, and clinical outcomes of breast implant capsule formation in a rabbit model and evaluate contamination during the surgical procedure. METHODS: Thirty-one New Zealand white female rabbits were each implanted with one tissue expander and two breast implants. The rabbits received (1) untreated implants and expanders (control; n = 10), (2) two implants sprayed with 2 mL of fibrin and one expander sprayed with 0.5 mL of fibrin (fibrin; n = 11), or (3) two implants inoculated with 100 µL of a CoNS suspension (10(8)CFU/mL-0.5 density on the McFarland scale) and one expander inoculated with a CoNS suspension of 2.5 × 10(7) CFU/mL (CoNS; n = 10). Pressure/volume curves and histological and microbiological evaluations were performed. Operating room air samples and contact skin samples were collected for microbiological evaluation. The rabbits were euthanized at four weeks. RESULTS: In the fibrin group, significantly decreased intracapsular pressures, thinner capsules, loose/dense (<25%) connective tissue, and negative/mild angiogenesis were observed. In the CoNS group, increased capsular thicknesses and polymorph-type inflammatory cells were the most common findings. Similar bacteria in capsules, implants, and skin were cultured from all the study groups. One Baker grade IV contracture was observed in an implant infected with Micrococcus spp. CONCLUSIONS: Fibrin was associated with reduced capsule formation in this preclinical animal model, which makes fibrin an attractive potential therapeutic agent in women undergoing breast augmentation procedures. Clinical strategies for preventing bacterial contamination during surgery are crucial, as low pathogenic agents may promote CC.

Effects of fibrin, thrombin, and blood on breast capsule formation in a preclinical model.

BACKGROUND: The root cause of capsular contracture (CC) associated with breast implants is unknown. Recent evidence points to the possible role of fibrin and bacteria in CC formation. OBJECTIVES: The authors sought to determine whether fibrin, thrombin, and blood modulated the histological and microbiological outcomes of breast implant capsule formation in a rabbit model. METHODS: The authors carried out a case-control study to assess the influence of fibrin, thrombin, and blood on capsule wound healing in a rabbit model. Eighteen New Zealand white rabbits received four tissue expanders. One expander acted as a control, whereas the other expander pockets received one of the following: fibrin glue, rabbit blood, or thrombin sealant. Intracapsular pressure/volume curves were compared among the groups, and histological and microbiological evaluations were performed (capsules, tissue expanders, rabbit skin, and air). The rabbits were euthanized at two or four weeks. RESULTS: At four weeks, the fibrin and thrombin expanders demonstrated significantly decreased intracapsular pressure compared to the control group. In the control and fibrin groups, mixed inflammation correlated with decreased intracapsular pressure, whereas mononuclear inflammation correlated with increased intracapsular pressure. The predominant isolate in the capsules, tissue expanders, and rabbit skin was coagulase-negative staphylococci. For fibrin and thrombin, both cultures that showed an organism other than staphylococci and cultures that were negative were associated with decreased intracapsular pressure, whereas cultures positive for staphylococci were associated with increased intracapsular pressure. CONCLUSIONS: Fibrin application during breast implantation may reduce rates of CC, but the presence of staphylococci is associated with increased capsule pressure even in the presence of fibrin, so care should be taken to avoid bacterial contamination.

Cardiac metastasis of melanoma as first manifestation of disease.

BACKGROUND: Metastatic tumors of the heart are 20 to 40 times more common than primary tumors. Metastases originate mainly in carcinomas and melanomas, the latter having the greatest propensity for cardiac involvement. On rare occasions this type of tumor may first manifest itself as a cardiac metastasis. METHODS: The authors present clinical, laboratory and imaging data from a patient with a cardiac mass that was the first manifestation of a melanoma. No other tumor location was detected by imaging studies. RESULTS: The patient presented with exertional dyspnea and tachycardia and was found to have a large mass in the right atrium. He underwent surgical removal of the tumor, but curative excision was not possible. A diagnosis of cardiac metastasis from malignant melanoma was made. The patient died soon afterwards from disseminated metastatic disease. CONCLUSIONS: This case represents a rare manifestation of melanoma located in the right atrium, with unknown origin of the primary tumor. Although surgery may be useful to palliate symptoms and improve survival in certain patients, it may also be associated with dissemination of the disease.