Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disorder, ultimately leading to respiratory failure and death. Despite great research advances in understanding the mechanisms underlying the disease, its diagnosis, and its treatment, IPF still remains idiopathic without known biological or histological markers able to predict disease progression or response to treatment. The histologic hallmark of IPF is usual interstitial pneumonia (UIP), with its intricate architectural distortion and temporal inhomogeneity. We hypothesize that normal lung alveolar architecture can be compared to fractals, such as the Pythagoras tree with its fractal dimension (D_f), and every pathological insult, distorting the normal lung structure, could result in D_f variations. In this study, we aimed to assess the UIP histologic fractal dimension in relationship to other morphometric parameters in newly diagnosed IPF patients and its possible role in the prognostic stratification of the disease. Clinical data and lung tissue specimens were obtained from twelve patients with IPF, twelve patients with non-specific interstitial pneumonia (NSIP), and age-matched “healthy” control lung tissue from patients undergoing lung surgery for other causes. Histology and histomorphometry were performed to evaluate D_f and lacunarity measures, using the box counting method on the FracLac ImageJ plugin. The results showed that D_f was significantly higher in IPF patients compared to controls and fibrotic NSIP patients, indicating greater architectural distortion in IPF. Additionally, high D_f values were associated with higher fibroblastic foci density and worse prognostic outcomes in IPF, suggesting that D_f may serve as a potential novel prognostic marker for IPF. The scalability of D_f measurements was demonstrated through repeated measurements on smaller portions from the same surgical biopsies, which were selected to mimic a cryobiopsy. Our study provides further evidence to support the use of fractal morphometry as a tool for quantifying and determining lung tissue remodeling in IPF, and we demonstrated a significant correlation between histological and radiological D_f in UIP pattern, as well as a significant association between D_f and FF density. Furthermore, our study demonstrates the scalability and self-similarity of D_f measurements across different biopsy types, including surgical and smaller specimens.

Background/Objectives: Acute Fibrinous and Organizing Pneumonia (AFOP) is a rare pulmonary condition histologically characterized by intra-alveolar fibrin deposition and organizing pneumonia without hyaline membranes. This study aims to describe the clinicopathologic and radiologic features of isolated AFOP nodules presenting as solitary pulmonary nodules (SPNs) mimicking malignancy in patients with recent COVID-19 infection. Methods: We retrospectively analyzed consecutive cases of histologically confirmed AFOP (n = 20) and organizing pneumonia (OP; n = 119) presenting radiologically as SPNs suspicious for malignancy from January 2021 to December 2023. Clinical data, COVID-19 status, radiologic features (including nodular characteristics, ground-glass opacity [GGO], and consolidation), and histopathological findings were collected and analyzed. Digital image analysis quantified the intra-alveolar fibrin content. Results: AFOP nodules showed a significant association with previous COVID-19 infection compared to OP (55% vs. 0.8%, p < 0.001). Radiologically, AFOP lesions were predominantly located in the upper lobes, frequently exhibiting a mixed pattern of GGO and consolidation within solitary nodules (8–28 mm diameter), distinctly differing from the predominantly lower-lobe homogeneous consolidations in OP. Histologically, AFOP was defined by prominent intra-alveolar fibrin “balls,” correlating significantly with radiological consolidation patterns (r = 0.991, p < 0.05). Regions of consolidation demonstrated higher fibrin contents compared to areas of predominant GGO. Conclusions: Isolated AFOP nodules presenting as SPNs post-COVID-19 infection strongly mimic malignancy radiologically, highlighting the necessity for multidisciplinary diagnostic approaches integrating radiological and histopathological data to avoid unnecessary interventions. Recognition of this rare but distinctive clinical entity is essential for appropriate patient management.

Background. Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is an autosomal dominant autoinflammatory disorder stemming from mutations in the TNFRSF1A gene affecting the tumor necrosis factor receptor (TNFR)-1. These mutations lead to dysregulated inflammatory responses, primarily mediated by augmented interleukin (IL)-1β release. Case Presentation. We present the case of a 29-year-old woman with a history of recurrent febrile episodes, abdominal pain, and joint manifestations, eventually diagnosed with TRAPS following genetic testing revealing a heterozygous R92Q mutation in TNFRSF1A. Further genetic examinations unveiled additional clinically significant mutations, complicating the clinical picture. Our patient exhibited delayed colonic transit time and right colonic amyloidosis, a rare complication. Surgical intervention was required for overwhelming intestinal obstruction, revealing mucosal atrophy and dense lymphocytic infiltrates on histological examination. Discussion. Gastrointestinal involvement in TRAPS is common but can present diagnostic challenges. Following colon resection, histological examination revealed amyloid deposition, underscoring the importance of a comprehensive evaluation of these patients. Isolated colic amyloidosis has significant diagnostic and prognostic implications, warranting cautious monitoring and tailored management strategies. Treatment of TRAPS typically involves anti-inflammatory agents such as IL-1 inhibitors, with our patient experiencing clinical improvement on anakinra and canakinumab. Conclusion. This case report emphasizes the diverse manifestations of TRAPS and the importance of recognizing gastrointestinal complications, particularly isolated colic amyloidosis. Comprehensive evaluation, including histological examination, is crucial for identifying atypical disease presentations and guiding management decisions. Continued research is needed to elucidate the underlying mechanisms and optimize treatment strategies for TRAPS and its associated complications.