Beyond diagnosis: exploring the significance of IgG4+ plasma cell count through immunostaining in IgG4-related disease.

OBJECTIVES: To evaluate whether the grade of IgG4+ plasma cell infiltration in biopsies is associated with clinical or serologic outcomes in IgG4-RD. METHODS: We included 57 patients with biopsy proven IgG4-RD according to the Comprehensive Diagnostic Criteria and/or the 2019 ACR/EULAR Classification Criteria. We collected histological, clinical (disease duration, phenotype, remission and relapses) and serological variables. RESULTS: 29 (50.9%) patients were men, mean age 49.9 years, with a median disease duration of 22 months. The distribution among clinical phenotypes were 14% pancreato-hepato-biliary, 12.3% retroperitoneal/aortic, 29.8% head and neck-limited, 29.8% Mikulicz/systemic and 14% undefined. Thirty-nine patients had a proliferative and 18 a fibrotic phenotype. Most biopsies were from lacrimal gland, lymph node, pancreas, orbit, kidney, retroperitoneum and thyroid gland. Thirty-nine (68.4%) patients had <100 IgG4+ plasma cells/HPF and 18 (31.6%) ≥100 IgG4+ plasma cells/HPF. Patients with ≥100 IgG4+ plasma cells/HPF were more likely to belong to the pancreato-hepato-biliary and the proliferative phenotypes, had fewer relapses and a higher remission rate. On multivariate analysis, the OR for remission at last follow-up was 6.7, 95% CI 1.1-4.42, p=0.03. The log-rank test showed a difference in relapse-free survival between the two groups (HR 2.6, 95% CI 1.2-5.6, p=0.01). According to the ROC analysis, patients with more than 61 IgG4+ plasma cells were less likely to relapse. CONCLUSIONS: A count of ≥100 IgG4+ plasma cells/HPF may identify patients with a proliferative phenotype, fewer relapses and a higher remission rate.

Major salivary gland enlargement in IgG4-related disease is associated with multiorgan involvement and higher basal disease activity.

Objective: To evaluate if major salivary gland enlargement in patients with IgG4-related disease (IgG4-RD) is associated with systemic involvement.Methods: We included 47 patients with diagnosis of IgG4-RD. We retrospectively collected demographics, organ involvement, disease activity and damage assessed by the IgG4-RD Responder Index (IgG4-RD RI) and treatment.Results: 25 patients (53%) were men, mean age 50.8 years and median disease duration 27 months. Most frequently anatomic sites affected were lymph nodes 55%, pancreas 51% and lacrimal glands 43%. We observed major salivary gland involvement in 22 (46.8%) patients. When we compared patients with (n = 22) vs. without (n = 25) salivary gland enlargement, the first group had a higher number of affected organs, a higher prevalence of lacrimal glands, lymph nodes, and lung involvement, rheumatoid factor positivity, azathioprine and prednisone use, as well as a higher baseline IgG4-RD RI and a longer delay in diagnosis. At logistic regression analysis we found an association of major salivary gland enlargement with the basal IgG4-RD RI (OR 1.37, 95%CI 1.09-1.61, p = .001) and with lacrimal gland involvement (OR 34.7, 95%CI 4.6-258, p = .001).Conclusion: Our study highlights the systemic nature of IgG4-RD. Patients with major salivary gland enlargement should be routinely screened for multi-organ disease.

Phosphaturic mesenchymal tumors. Survey of 8 cases from a single Mexican medical institution.

Phosphaturic mesenchymal tumor (PMT) is a morphologically heterogeneous soft tissue and bone neoplasm, producing a paraneoplastic syndrome due to phosphate wasting. These tumors produce fibroblast growth factor 23, which is implicated in renal tubule phosphate loss. Medical records of patients seen from 1999 to 2013 with osteomalacia associated or not with a tumor were reviewed. Clinical and laboratory data, radiographic studies, and follow-up of 8 patients were tabulated. Histologic features and the immunoprofile of the tumors were analyzed. There were 208 patients with osteomalacia, but only 8 (3.84%) had osteomalacia associated with a tumor. The median age of the patients was 40 years. The tumor size ranged from 1.5 to 4 cm. Five were located in soft tissues and skin; and 3, in bones. Osteomalacia symptoms lasted from 2 to 14 years with a median of 6 years. Laboratory data showed hypophosphatemia and phosphaturia in all patients. All tumors were histologically benign. Histologically, the salient features were a hemangiopericytoid pattern, chronic hemorrhage, and microcystic areas. All neoplasms were diffusely positive for vimentin and focally positive for epithelial membrane antigen, CD34, and S-100 protein. Ki-67 was positive in approximately 10% of neoplastic cells in 2 cases and less than 1% in the remainder. We report 8 cases of PMTs producing osteomalacia, from a single third-level Mexican medical institution. These tumors occurred in soft tissues, skin, and bones. All tumors were benign, small, not easily detected by physical examination and diagnosed due to the metabolic abnormalities.

Indolent T-cell Lymphoproliferative Disorder of the Gastrointestinal Tract Mimicking Crohn's Disease.

Indolent clonal T-cell lymphoproliferative disorder (iCTLD-GI)/indolent T-cell lymphoma of the gastrointestinal tract (iTLP-GI) poses diagnostic challenges, and despite its rarity, accurate diagnosis is crucial for appropriate management. We report the case of 34-year-old female with a 19-year history of gastrointestinal symptoms suggestive of inflammatory bowel disease (IBD). Subsequent evaluation revealed iCTLD-GI/iTLP-GI with extensive Crohn's disease-like morphological alterations, previously unreported. These macroscopic and microscopic aspects underscore the need for a comprehensive evaluation to avoid misdiagnosis with IBD. Additionally, molecular studies have identified potential therapeutic targets, highlighting the evolving management strategies. This case underscores the diagnostic complexity of iCTLD-GI/iTLP-GI, especially when the condition mimicks IBD such as Crohn's disease.

Spindle epithelial tumor with thymus-like differentiation of the thyroid (SETTLE): Report of two cases (one associated with a parathyroid adenoma).

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare tumor usually localized in the thyroid gland and perithyroid tissues. It is considered to arise from ectopic thymic tissue or branchial pouch remnants. It occurs more frequently in children and adolescents. We report 2 cases of spindle epithelial tumor with thymus-like differentiation localized in the thyroid gland, and 1 of them was associated with a parathyroid adenoma. We emphasize the need for a close and long-term follow-up in these patients.

Inflammatory myofibroblastic tumor of the liver.

 Hepatic inflammatory myofibroblastic tumors are uncommon low grade malignant neoplasms. They can be confused clinically and by imaging studies with abscess.

Thyroid-like cholangiocarcinoma of the liver: an unusual morphologic variant with follicular, trabecular and insular patterns.

We report the case of a 26-year-old woman with a 19 cm malignant hepatic neoplasm with morphological features that closely resembled a follicular thyroid carcinoma. Despite this, it was interpreted as a cholangiocarcinoma due to the absence of a primary thyroid tumor and the lack of thyroglobulin and TTF-1 immunoreactivity by the hepatic tumor. The left hepatic lobectomy specimen showed an encapsulated and multinodular gray-white mass with cystic and hemorrhagic areas. Microscopically, it displayed predominant macro and microfolicullar patterns with focal solid, trabecular and insular areas. The small and distended follicles contained a colloid-like secretion and were lined by low cuboidal cells with scant cytoplasm, round or oval hyperchromatic nuclei with fine chromatin. The solid areas, trabecular and insular structures were similar to those of follicular or papillary thyroid carcinomas. In addition, some of the neoplastic cells had clear nuclei with occasional grooves. The tumor was positive for cytokeratin (CK) 7, CK 19 and CD138, and negative for TTF-1, thyroglobulin, Hepar-1, Glypican-3, alpha-fetoprotein and neuroendocrine markers. A thyroid neoplasm was excluded clinically and by ultrasound and computed tomography. Although, the residual hepatic parenchyma was initially not cirrhotic, the patient eventually developed cryptogenic cirrhosis. The patient received adjuvant chemotherapy and died of metastatic disease 18 months after surgery. The thyroid-like pattern broadens the morphologic spectrum of cholangiocarcinoma.

Multiple venous and arterial thromboses of the gallbladder causing acute cholecystitis. A previously undescribed complication of essential thrombocythemia.

Well established complications of essential thrombocythemia are multiple thrombohemorrhagic phenomena in various abdominal organs. We describe the case of a 22 year old man with essential thrombocythemia and thrombosis of the mesenteric and splenic veins as well as cavernomatous transformation of the portal vein. The patient also had a splenic infarction and a subphrenic hematoma. Additionally, he developed signs and symptoms of acute cholecystitis which in turn led to an open cholecystectomy. The gallbladder had a markedly thickened wall due to multiple recent and recanalized thrombi predominantly in subserosal veins. Only a few arteries were occluded by thrombi. A marked vascular proliferation in the subserosal connective tissue mimicking a hemangioma was most likely the result of collateral circulation. There was also a mild acute and chronic inflammatory infiltrate and edema in the lamina propria of the gallbladder. Hyperplasia of interstitial cells of Cajal in the lamina propria and between smooth muscle cells and proliferation of nerve trunks in the subserosal connective tissue adjacent to the thrombosed veins and arteries was also noted. To our knowledge this unique gallbladder thrombotic complication of essential thrombocythemia has not been previously reported.

Unusual metastases of papillary thyroid carcinoma: report of 2 cases.

We present 2 cases of papillary thyroid carcinoma (PTC) with conventional morphology that metastasized to unusual sites. The first neoplasm was a PTC whose initial clinical manifestation was a large metastasis in the pancreas which mimicked a primary neoplasm. The mediastinal location of the thyroid gland was responsible for the delay in identification of the primary tumor. Eventually, the patient, a 72-year-old man, developed brain and vertebral metastases. The second case was that of a 58-year-old woman with a PTC with initial metastases in cervical lymph nodes; subsequently, the tumor spread to axillary lymph nodes and finally to the breast. Transformation to anaplastic spindle and giant cell carcinoma within the breast metastasis occurred 20 years after the primary thyroid tumor had been diagnosed and surgically treated. The metastatic anaplastic spindle and giant cell carcinoma contained rhabdoid inclusions further complicating identification. To the best of our knowledge, only 3 cases of PTC metastatic to the breast have been reported, none of them with anaplastic transformation. On the other hand, only 3 cases of PTC metastatic to the pancreas have been published, 2 of them of the tall cell variant, and in none of these cases were the first symptoms attributable to the metastasis. Brief comments about the differential diagnosis are included.

Inverted urothelial papilloma of the urinary bladder with focal papillary pattern: a previously undescribed feature.

We report 2 examples of inverted urothelial papillomas with a focal papillary pattern. Both patients, a 43-year-old man and a 13-year-old adolescent boy, presented with hematuria. In addition to the characteristic trabecular endophytic growth pattern and bland cytologic features, the tumors showed focal papillary architecture in the endophytic component. Because of this feature, both tumors were misinterpreted as papillary urothelial carcinoma with inverted pattern. However, the papillary fronds were similar to those of exophytic urothelial papilloma. They were lined by 3 to 8 layers of normal-appearing urothelial cells often covered by a continuous or discontinuous layer of superficial (umbrella) cells. Although follow-up is limited, the 2 patients have remained asymptomatic. The recognition of papillary structures in urothelial inverted papilloma broadens the morphological spectrum of this unusual benign urothelial neoplasm and complicates the microscopic interpretation of urothelial lesions with inverted growth patterns. Surgical pathologists should be aware of this unusual feature of inverted urothelial papilloma of the urinary bladder to avoid misinterpretation with urothelial carcinoma with an inverted pattern.

Malignant Shamblin III Carotid Body Tumors Resected with Use of the Retrocarotid Dissection Technique in 2 Patients.

Carotid body tumors are rare neoplasms with malignant potential in 6% to 12.5% of cases, and surgical resection is the only cure. We present the cases of 2 female patients who had expanding, painless, right-sided neck masses; computed tomographic angiograms revealed Shamblin III tumors at the carotid bifurcation. Each patient underwent tumor resection with use of the retrocarotid dissection technique. The tumor specimens were histologically consistent with malignancy, and free margins were achieved. The patients remained free of symptoms, local recurrence, and metastasis 44 and 19 months after their respective procedures. These are the first malignant Shamblin III carotid body tumors that we have resected by means of retrocarotid dissection. In addition to our patients' cases, we discuss carotid body tumors and compare the retrocarotid and standard caudocranial resection techniques.

[Peutz-Jeghers syndrome]. / Síndrome de Peutz-Jeghers.

OBJECTIVE: To describe the demographic, clinical characteristics and associated diseases in eight patients with the Peutz-Jeghers syndrome seen at the INCMNSZ and literature review. SETTING: National Institute of Health. DESIGN: Description of eight cases of Peutz-Jeghers syndrome and literature review. MATERIAL AND METHODS: A retrospective review of all the discharge diagnosis was doing between January 1987 to February 2004. The diagnosis of Peutz-Jeghers syndrome was made on clinical and anatomical grounds. The clinical features, follow-up, treatment and last visit clinical status were analyzed in all the patients. PRESENTATION OF CASES: Eight patients with the Peutz-Jeghers syndrome were investigated, five women and three men. The median of time at diagnosis was 31 years-old (range, 26-37). All the patients had mucocutaneous pigmentation and hamartomatous polyps. The ileum and large bowel were the most frequent sites of the polyps, and there were generally sessile and pedunculated. The major abdominal symptoms were abdominal pain, GI bleeding, intestinal obstruction, weight loss and intussusception. One case of small-bowel cancer and one of serous cystadenoma of the ovary were detected. Surgical interventions were doing in five patients; the most frequent indication was polyp-induced bowel obstruction. All the patients are alive to date.

[Endocrine neoplasm of the stomach. Study of thirteen cases]. / Tumores endocrinos del estómago. Análisis de 13 casos.

A Thirteen patients with primary endocrine neoplasm of the stomach were studied for 20 years. Six patients were male and 7 female with an age range of 33 to 77, mean age 57 years. Nine cases corresponded to well differentiated carcinoids and four to neuroendocrine carcinomas. Of the former, three were sporadic and six were associated with atrophic gastritis. These two forms of neoplasm showed important differences: those associated with atrophic gastritis had hypergastrinemia, all of the multiple small tumors confined to the corpus and fundus were well differentiated carcinoids associated with intestinal metaplasia and G cell hyperplasia in antrum and ECL cell hyperplasia in corpus and fundus. Tumors were clinically benign, with an excellent prognosis. All patients are currently alive with no evidence of neoplasm. In only one of these cases, antiparietal cell antibodies were documented; in three of them, extensive intestinal metaplasia probably due to Helicobacter pylori infection was found. In contrast, sporadic carcinoids were large isolated tumors originating in the antrum or corpus. Two patients died as a consequence of the neoplasm; all of them were moderately differentiated and in none of the cases we found evidence of endocrine hyperplasia. All were positive for generic endocrine markers and were focally positive to some of the specific hormone markers. Al four neuroendocrine carcinomas had a clinical course similar to that of gastric adenocarcinomas and were poorly differentiated large tumors. We conclude that gastric carcinoids associated with atrophic gastritis have an excellent prognosis. On the other hand, neuroendocrine carcinomas have a very poor prognosis with fatal outcome of patients. Sporadic carcinoids have an intermediate prognosis.

[Role of laparoscopy with ultrasound in the staging process of pancreatic and ampullary tumors]. / Utilidad de la laparoscopía con ultrasonido en la evaluación de resecabilidad de los tumores pancreáticos y ampulares.

Computarized tomography allows proper identification and evaluation of stage in the majority patients with periampullary tumors. However, 30% of peritoneal metastases cannot be seen in image studies. The aim of the present study was to evaluate the role of laparoscopy with laparoscopic ultrasound in the staging process of pancreatic and ampullary tumor. Diagnostic laparoscopy was performed on 20 patients included in the study Mean age was 58.35 +/- 13.4 years. Twelve were males and eight females. In two patients, laparoscopy showed peritoneal metastases and ultrasound did not show extrapancreatic involvement. In five patients, there was vascular invasion without metastases. In three patients, both peritoneal metastases and vascular invasion were found, and in five there was neither vascular invasion nor metastasis. Laparoscopic findings were confirmed in a but one patient. In 14 of the 16 patients In whom peritoneal lavage was performed, microscopic exam showed a sufficient number of cells to make a diagnosis. We concluded that laparoscopy with ultrasound is useful in staging of patients with duodeno-bilio-pancreatic malignancies.

Clinical and Immunopathologic Profile of Mexican Patients with IgG4 Autoimmune Pancreatitis.

Autoimmune pancreatitis is part of the spectrum of IgG4-associated diseases. Its diagnostic criteria and histological subtypes have been formally proposed recently and although based on current data it has been suggested that there are differences in clinical presentation among populations, more research is needed to properly establish if this heterogeneity exists. In this paper, we describe 15 cases of autoimmune pancreatitis diagnosed at a Mexican centre of reference, all of them associated to the lymphoplasmocytic sclerosing pancreatitis variant. The mean age at the onset of symptoms was 47.5 ± 14.4 years, and 53% of patients were male. The main manifestations were weight loss (87%), obstructive jaundice (53%), and acute (27%) and chronic (27%) pancreatitis. Only 20% of patients had high IgG4 serum levels at the time of diagnosis. All patients receiving prednisone responded favourably, both in their pancreatic and extrapancreatic manifestations. Clinical manifestations of Mexican patients showed certain differences with respect to those usually reported.

Polypoid Brenner tumor of the uterus.

Extraovarian Brenner tumors (BT) are very rare. We report such a tumor that was an intracavitary polyp in the uterus of a 63-year-old woman. The differential diagnosis included a pure transitional cell tumor, a mixed mullerian tumor, and a uterine tumor resembling an ovarian sex cord tumor. The histogenesis of BT remains controversial; in this particular case the location of the BT suggests a mullerian origin.

Adenomatoid Tumor of the Right Adrenal Gland in a Patient with AIDS.

An autopsy case with an incidentally discovered adenomatoid tumor (AT) arising in the right adrenal gland of a 34-yr-old man with AIDS is presented. The immediate cause of death was disseminated coccidioidomycosis. The affected right adrenal gland was partially substituted by a firm 3.O cm nodule enclosed by cortical adrenal tissue. Histologically, the tumor had the typical appearance of those adenomatoid neoplasms described in the genital tract. The mesothelial origin of the neoplasm was confirmed by immunopositive cells for low weight cytokeratin and vimentin. Uncommon neoplasms in the adrenal glands of AIDS patients include leiomyosarcomas, leiomyomas, and malignant nerve sheath tumors. This report may represent the first case of an adrenal gland AT in a patient with AIDS, and probably the third well-documented histologically and immunohistochemically adrenal gland AT.