A Rare Case of Subcutaneous Amyloidoma Associated with Localized Lymphoplasmacytic Lymphoma: Diagnostic Challenges and Treatment Considerations.

BACKGROUND AL amyloidomas are solitary, localized, tumor-like deposits of immunoglobulin light-chain-derived amyloid fibrils in the absence of systemic amyloidosis. A rare entity, they have been described in various anatomical sites, typically in spatial association with a sparse lymphoplasmacytic infiltrate, ultimately corresponding to a clonal, malignant, lymphomatous disorder accounting for the amyloidogenic activity. Most frequently, the amyloidoma-associated hematological disorder corresponds to either a solitary plasmacytoma or an extranodal marginal zone lymphoma of MALT. Much rarer is the association with lymphoplasmacytic lymphoma, which by itself is usually a bone marrow-bound disorder with systemic burden. The almost anecdotic combination of an amyloidoma and a localized lymphoplasmacytic lymphoma deserves attention, as it entails a thorough diagnostic workup to exclude systemic involvement and a proportionate therapeutic approach to avoid overtreatment. A review of the literature provides an insight on pathogenesis and prognosis, and can assist both pathologists and clinicians in establishing optimal patient management strategies. CASE REPORT We herein report the incidental finding of a subcutaneous amyloidoma caused by a spatially related, similarly localized lymphoplasmacytic lymphoma diagnosed in a 54-year-old female patient with no other disease localizations and a complete remission following 2 subsequent surgical excisions. CONCLUSIONS Whatever the specific combination of an amyloidoma and the related hematological neoplasm, a multidisciplinary collaboration and a comprehensive clinical-pathological staging are warranted to exclude systemic involvement and identify patients with localized diseases who would benefit from local active treatment and close follow-up.

Patient-reported Outcomes and Disability Are Associated with Histological Disease Activity in Patients with Ulcerative Colitis: Results from the APOLLO Study.

BACKGROUND AND AIMS: Treating beyond endoscopic remission, aiming for histological remission, is an emerging target in ulcerative colitis [UC]. Patient-reported outcome measurements [PROMs] become increasingly important, but their association with histology is unclear. METHODS: Multiple PROMs were prospectively collected in UC patients undergoing colonoscopy. Mayo endoscopic sub-score [MES] and ulcerative colitis endoscopic index of severity [UCEIS] were determined, as well as the Nancy histological index [NHI] of the most affected area. Endoscopic remission was defined as MES and UCEIS 0, histological remission as NHI 0, and histo-endoscopic mucosal remission [HEMR] as a combination of both. RESULTS: A total of 109 assessments were collected in 80 patients with endoscopic and HEMR remission rates of 24.8% and 16.5%, respectively. Patients with HEMR had a significantly lower overall inflammatory bowel disease [IBD] disability [p <0.001] and disease activity score [p <0.001] as compared with patients without. In line, NHI correlated with the overall IBD-disk [r = 0.36, p <0.001] and simple clinical colitis activity index [SCCAI] score [r = 0.44, p <0.001]. Many individual components of both differed significantly between patients with and without HEMR. Although the overall accuracy of the IBD-disk [0.78] or SCCAI score [0.83] for HEMR is lower [p <0.005] than the MES or UCEIS [0.95], a cumulative IBD-disk score >35.5 and an SSCAI score >3.5 have a high negative predictive value [98.6% and 100.0%, respectively] to exclude HEMR. CONCLUSION: Histo-endoscopic inactive disease is associated with reduced IBD disability, but not with complete absence thereof. PROMs for disability and clinical disease activity cannot fully replace histo-endoscopic findings, and should be considered complementary in patient-centred endpoint discussions. Nevertheless, PROMs have a high negative predictive value to rule out HEMR.

68Ga-DOTATATE PET/CT Distinguishes Neuroendocrine Tumor Mesenteric Lymph Node Metastasis From an Extensive IgG4-Positive Fibrosis Surrounding It.

ABSTRACT: A 56-year-old woman presented with right iliac fossa pain. Abdominal CT showed a mesenteric mass in the right iliac fossa, adjacent to the vena cava inferior and right ureter. Biopsy of the mass revealed a well-differentiated neuroendocrine tumor. 68Ga-DOTATATE PET/CT showed strong somatostatin receptor expression only within in a small, central area of this mesenteric mass, with faint 68Ga-DOTATATE uptake in the majority of this mesenteric mass. Pathology revealed an IgG4-positive storiform fibrosis surrounding a mesenteric adenopathy. 68Ga-DOTATATE PET/CT discriminates between neuroendocrine tumor lymph node metastases and fibrosis, hereby avoiding potential sampling error of tumor biopsies and guiding surgical approach.

Curious Residents of the Thyroid Gland: Two Case Reports of Colorectal Carcinoma Metastasis by Fine-Needle Aspiration Diagnosis.

BACKGROUND: The most frequent metastases to the thyroid originate in the kidney, lung or breast. Colorectal adenocarcinoma represents less than 4% of metastases to the thyroid gland. Solitary metastases of colorectal cancer with no other manifestation of disseminated cancer disease are exceedingly rare. Within the Bethesda Classification for Reporting -Thyroid Cytopathology, metastases are included in Diagnostic Categories "Suspicious for Malignancy" and "Malignant." CASES: We present 2 cases of colorectal adenocarcinoma metastatic to the thyroid gland, diagnosed by fine-needle aspiration (FNA). One metastasis occurred in normal thyroid parenchyma; the other was a tumour-to-tumour metastasis into a follicular carcinoma of the thyroid. The latter is the first published tumour-to-tumour metastasis of a colorectal carcinoma in the thyroid from which both components were diagnosed by FNA. CONCLUSION: Diagnosing a metastasis to the thyroid is challenging. On FNA, a dual cell population should raise suspicion. Immunocytochemical and molecular analysis may be helpful. Clinical information is essential in guiding specific ancillary technique panels in scant cellular material.

In vivo activation of gelatinase B/MMP-9 by trypsin in acute pancreatitis is a permissive factor in streptozotocin-induced diabetes.

Matrix metalloproteinases, in particular gelatinase B/MMP-9, are key mediators in autoimmune diseases like multiple sclerosis and rheumatoid arthritis, but their pathogenic roles in diabetes are not well established. Gelatinase B has previously been shown to be upregulated in pancreas tissue from patients with acute and chronic pancreatitis and was suggested to exacerbate diabetes by cleaving insulin. In this study, the role of gelatinase B in diabetes was investigated using two streptozotocin-induced animal models of type I diabetes. In both a hyperacute and a subacute model, gelatinase B upregulation was found to be associated with disease activity. However, gelatinase B deficiency did not significantly protect against diabetes development, and wild-type and gelatinase B-deficient animals behaved similarly in terms of beta-cell apoptosis or necrosis. The fact that gelatinase B was found almost exclusively as the inactive pro-enzyme in most of the streptozotocin-induced diabetic animals may explain the lack of a gelatinase B effect. On the contrary, gelatinase B was completely activated in a minority (15%) of wild-type animals. This coincided with exocrine pancreatic inflammation, as revealed by the presence of active trypsin. The discovery of in vivo activation of progelatinase B by trypsin in acute pancreatitis is extended in a model of caerulein-induced pancreatitis. In the latter model, trypsinogen activation is systematically achieved and gelatinase B is found in its active form. In conclusion, gelatinase B itself is not a causative factor but, when activated by endogenous trypsin, is a permissive factor for insulin degradation and diabetes.

Gelatinase B is diabetogenic in acute and chronic pancreatitis by cleaving insulin.

Genetic, endocrine, and environmental factors contribute to the development of diabetes. Much information has been gathered on the homeostasis mechanisms of glucose regulation by insulin-producing pancreatic beta cells. Here we demonstrate high expression levels of gelatinase B (matrix metalloproteinase-9, MMP-9) by neutrophils in acute pancreatitis and by ductular epithelial cells in chronic pancreatitis. Because gelatinase B processes cytokines and chemokines, we investigated whether and how gelatinase B cleaves insulin. Pure human neutrophil gelatinase B was found to destroy insulin by cleavage at 10 sites. Pancreatic islet and ductular cells are relatively spared in comparison with the complete destruction of acinar cells of the exocrine pancreas in chronic pancreatitis. High expression levels of gelatinase B are maintained in the immediate proximity of insulin-secreting beta cells. Consequently, diabetes may be worsened by enzymatic degradation of insulin by gelatinase B and by the consequent enhancement of the autoimmune process. Gelatinase B is diabetogenic in acute and chronic pancreatitis by cleaving insulin.