Pancreatic cystic lesions (PCLs) pose a diagnostic challenge due to their increasing incidence and the limitations of cross-sectional imaging and endoscopic-ultrasound-guided fine-needle aspiration (EUS-FNA). EUS-guided through the needle biopsy (EUS-TTNB) has emerged as a promising tool for improving the accuracy of cyst type determination and neoplastic risk stratification. EUS-TTNB demonstrates superior diagnostic performance over EUS-FNA, providing critical preoperative information that can significantly influence patient management and reduce unnecessary surgeries. However, the procedure has risks, with an overall adverse event rate of approximately 9%. Preventive measures and further prospective studies are essential to optimize its safety and efficacy. This review highlights the potential of EUS-TTNB to enhance the diagnostic and management approaches for patients with PCLs. It examines the current state of EUS-TTNB, including available devices, indications, procedural techniques, specimen handling, diagnostic yield, clinical impact, and associated adverse events.

Due to their aspecific macroscopic appearance, uncommon pancreatic cystic lesions (PCLs) are often misdiagnosed as mucinous lesions and improperly resected. We aimed to evaluate the endoscopic ultrasound (EUS)-guided through-the-needle biopsy (TTNB) capacity of the preoperative diagnosis of uncommon PCLs. Overall, 136 patients with PCLs who underwent EUS-TTNB between 2016 and 2022 were retrospectively identified. Common histotypes (e.g., IPMN, serous cystadenoma, and mucinous cystadenoma) were excluded and 26 (19.1%) patients (15 female, mean age 52.9 ± 10.4) were analyzed. The EUS findings, adverse events (AEs), and TTNB outcomes in uncommon PCLs were evaluated. The cysts histotype was accurately diagnosed by TTNB in 24/26 (92.3%) cases (seven cystic neuroendocrine tumors, four squamoid cysts, three acinar cells cystadenomas, two lymphoepithelial cysts, two mucinous non-neoplastic cysts, two bronchogenic cysts, two cystic lymphangiomas, one solid-pseudopapillary neoplasm, and one schwannoma). In the remaining two cases, lymphangioma was eventually diagnosed after resection. Surgery was performed in 15/26 (57.7%) patients. The mean follow-up of non-surgical patients was 32.5 months. One severe acute case of pancreatitis (3.8%) that required surgery occurred after EUS-TTNB. Uncommon pancreatic/peripancreatic lesions represent the 19.1% of PCLs in our series, with mainly benign histotypes. TTNB demonstrated a high diagnostic performance with a low rate of AEs in this setting, representing a reliable tool with which to avoid useless surgery.

Background: IgG4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory disorder characterized by lymphoplasmacytic infiltrates enriched in IgG4-positive plasma cells, storiform fibrosis, and frequently elevated serum IgG4 levels. Classic forms, such as pancreaticobiliary or retroperitoneal involvement, are often recognized early, whereas atypical manifestations mimic malignancy or inflammatory conditions, leading to delayed or inappropriate treatment. Case Series: A 30-year-old man presented with hyperemesis, proptosis, and gait instability. He was found to have colonic stenosis, stomach thickening, pachymeningitis, and polyserositis. Gastroenteric histology and serology confirmed IgG4-RD. Steroids were ineffective, but rituximab produced sustained clinical and radiologic improvement. A 35-year-old woman developed jaundice and cholestasis with a perihilar mass highly suggestive of cholangiocarcinoma. Histopathology revealed IgG4-RD, and rituximab therapy led to marked clinical and serological improvement. A 64-year-old woman with a submandibular mass underwent sialoadenectomy, with histology confirming IgG4-RD; she remained asymptomatic without systemic treatment. Literature Review: A literature review highlighted the diagnostic challenges of atypical IgG4-RD. Gastrointestinal involvement is rare and often misclassified as inflammatory bowel disease. Isolated biliary disease frequently mimics cholangiocarcinoma, while salivary gland involvement may be misdiagnosed as neoplasia. Serum IgG4 levels >135 mg/dL and IgG4/IgG ratio >0.21 may support clinical suspicion, but histopathology remains indispensable for definitive diagnosis and for excluding malignancy. Steroid responsiveness is a hallmark, though relapses after tapering are common, often necessitating B-cell-directed therapy. Conclusions: IgG4-RD should be considered in patients with unexplained, relapsing, or steroid-responsive conditions. Early recognition, multidisciplinary collaboration, and integration of histopathology with clinical features are essential to avoid misdiagnosis and optimize management.

Primary localized nodular cutaneous amyloidosis (PLCNA) is the rarest form of cutaneous amyloidosis caused by immunoglobulin light-chain amyloid protein deposition in the dermis, subcutis, and blood vessels.[1] A 49-year-old Caucasian woman, affected by a form of undifferentiated connective tissue disease since the age of 22 years, presented to our clinic with a two-month history of ulcerated nodule of the scalp. Although the patient complained daily Raynaud’s phenomenon, puffy hands, xerophthalmia and xerostomia, she was not receiving any pharmacological treatment. Clinical examination revealed a 20-mm painful, ulcerated, and crusted alopecic nodule in the vertex. The nodule was orange-pink in color and firm in consistence. Two satellite lesions were noticed at the periphery. Dermoscopy revealed short ectatic vessels and shiny whitish fibrotic areas on a yellow-orange background. Histology showed an extensive deposition of eosinophilic amorphous material in the dermis, subcutis, and blood vessels. Focal areas of calcification, rare plasma cells, and neovascularization within the dermis were observed. At polarized microscope, Congo red staining revealed apple green birefringence indicating amyloid protein deposition. The patient had anemia (hemoglobin 9.9 g/dL) and mild increase of erythrocyte sedimentation rate (23 mm/h). C-reactive protein, complement (C3, C4 and CH50), and blood urea nitrogen levels were within the normal range, as well as urinalysis and 24-h urine testing for creatinine clearance and protein excretion. Serum and protein electrophoresis and urinary BenceJones protein were negative for monoclonal components. Complete metabolic panel and liver function tests were within the normal range. Serum antinuclear antibodies (ANA) were present at title of 1/1280 (centromeric pattern), as well as anti-double-stranded deoxyribonucleic acid (anti-dsDNA) (41 UI/mL). Among anti-extractable nuclear antigen, antiSSA (Ro60 and Ro52), and anti-SSB were positive, at title of 1/1375, 1/1685 and 1/154 respectively. Capillaroscopy showed elongated loops and pericapillary edema. A salivary gland biopsy excluded Sjögren syndrome and amyloidosis deposits. Calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome was also ruled out, as there was no evidence of esophageal dysmotility, sclerodactyly, and cutaneous telangiectasias. Total body computed tomography scan and laboratory results excluded systemic manifestations of amyloidosis. A concomitant diagnosis of systemic erythematosus lupus was finally made. The nodules were treated with electrodessication and cryosurgery; however, four months later, the primary lesion relapsed. The patient underwent radical surgical excision and full-thickness skin graft. Meanwhile, she was treated with hydroxychloroquine 200 mg twice/day and a four-month systemic corticosteroid course (prednisone 1 mg/kg/day). No clinical and dermoscopic relapse was detectable at two years of follow-up, after a maintenance treatment with hydroxychloroquine 200 mg a day. A written informed consent was obtained from the patient. Primary localized nodular cutaneous amyloidosis is the rarest form of primary localized cutaneous amyloidosis, accounting for 1.5% of all cases, and differentiates fromthe other forms (lichen amyloidosis and macular amyloidosis), since amyloid deposits are not cytokeratin-derived, but originate from immunoglobulin light chains produced by dermal plasma cell infiltrates.[1,2] In general, PLCNA presents as waxy, skin-colored or orange nodules, usually located on the acral extremities.[3] In case of scalp involvement, the differential diagnosis may include cutaneous metastasis, non-melanoma skin cancer, Merkel cell carcinoma, and primary cutaneous B-cell lymphoma.[2] It also shares dermoscopic features of granulomatous disorders including orange background and teleangectasic vessels. Reddish structureless and whitish area and ulcerations were also reported.[4] Different reports have described that PLCNA is frequently associated with autoimmune disease, particularly Sjögren syndrome. A plasma cell dyscrasia, possibly elicited by autoimmune disease, may induce the local production and deposition of immunoglobulin light chains. Although most PLCNA cases are limited to the skin, progression to systemic disease has been reported and clinical monitoring may be recommended.[5] Cryosurgery, electrodessication, carbon dioxide and pulsed-dye, as well as surgical excision laser have been employed, although relapse is not rare.[1]

Objectives: This article aims to define the clinical, radiological, and pathological characteristics of non-resorbed oxidised cellulose-induced pseudotumours to raise awareness among surgeons and radiologists, to prevent misdiagnosis, and avoid unnecessary invasive procedures and delays in adjuvant oncological treatments. Methods: A systematic review of oxidised resorbable cellulose (ORC)-induced pseudotumours of the head and neck was conducted following PRISMA 2020 guidelines. Articles were retrieved from PubMed, Scopus, Cochrane, and Web of Science. Two ORC-induced pseudotumour cases from the Maxillofacial Surgery Department of Verona are also presented. Results: In most cases, pseudotumours were monitored using ultrasound. Further investigations included CT, MRI, PET-CT, and scintigraphy. Ultrasound images showed stable, elongated, and non-homogeneous masses. In CT scans, pseudotumours showed a liquefied core, and none or only peripheral enhancement. In MRI, pseudotumours presented none or only peripheral enhancement, and a heterogeneous pattern in T2-weighted images. 18-FDG PET scans demonstrated an FDG-avid mass (SUV 7.5). Scintigraphy was inconclusive. Cytology indicated a granulomatous reaction without neoplastic cells. Where surgical excision was performed, a granulomatous reaction with the presence of oxidised cellulose fibres was confirmed. Conclusions: Surgeons should consider artifacts from retained oxidised absorbable haemostatic material when suspecting tumour recurrence or metastasis on postoperative imaging, especially if certain features are present. Fine-needle aspiration cytology (FNAC) is a useful diagnostic tool, but surgical excision may be needed if FNAC is inconclusive or impractical. Collaboration between surgeons and radiologists is essential to avoid misdiagnosis and delays in treatment. Documenting the use and location of haemostatic material in operative reports would aid future understanding of these phenomena.