Diffuse Hyperplasia Research Articles

PDGFRA-mutant syndrome

Germline PDGFRA mutations cause multiple heterogeneous gastrointestinal mesenchymal tumors. In its familial form this disease, which was formerly termed intestinal neurofibromatosis/neurofibromatosis 3b (INF/NF3b), has been included among familial gastrointestinal stromal tumors (GISTs) because of its genotype, described when GIST was the only known PDGFRA-mutant gastrointestinal tumor. Shortly afterwards, however, inflammatory fibroid polyps also revealed PDGFRA mutations. Subsequently, gastrointestinal CD34+ ‘fibrous tumors’ of uncertain classification were described in a germline PDGFRA-mutant context. Our aim was to characterize the syndrome produced by germline PDGFRA mutations and establish diagnostic criteria and management strategies for this hitherto puzzling disease. We studied a kindred displaying multiple gastrointestinal mesenchymal tumors, comparing it with published families/individuals with possible analogous conditions. We identified a novel inherited PDGFRA mutation (P653L), constituting the third reported example of familial PDGFRA mutation. In adult mutants we detected inflammatory fibroid polyps, gastric GISTs and gastrointestinal fibrous tumors of uncertain nosology. We demonstrate that the syndrome formerly defined as INF/NF3b (exemplified by the family reported herein) is simplistically considered a form of familial GIST, because inflammatory fibroid polyps often prevail. Fibrous tumors appear variants of inflammatory fibroid polyps. ‘INF/NF3b’ and ‘familial GIST’ are misleading terms which we propose changing to ‘PDGFRA-mutant syndrome’. In this condition, unlike KIT-dependent familial GIST syndromes, if present, GISTs are stomach-restricted and diffuse Cajal cell hyperplasia is not observed. This restriction of GISTs to the stomach in PDGFRA-mutant syndrome: (i) focuses oncological concern on gastric masses, as inflammatory fibroid polyps are benign; (ii) supports a selective role of gastric environment for PDGFRA mutations to elicit GISTs, justifying the known predilection for stomach of sporadic PDGFRA-mutant GISTs. An awareness that inflammatory fibroid polyps, relatively common among gastrointestinal mesenchymal tumors, may be the prevailing tumor in PDGFRA-mutant syndrome could eventually reveal an unsuspected prevalence of this condition.

Gut wall replacing type of gastrointestinal stromal tumor presenting as a perforation of the ileal diverticulum

Gastrointestinal stromal tumors (GISTs) usually form a well-circumscribed mass. Very rarely, however, sporadic GISTs show gut-wall replacing growth, similar to the diffuse hyperplasia of interstitial cells of Cajal (ICC) observed in patients with neurofibromatosis type 1 (NF1) and hereditary GIST. Here we describe a patient with ileal perforation caused by this unusual type of GIST. An 82-year-old man was admitted to the emergency department with sudden abdominal pain. Following a provisional diagnosis of perforation of Meckel's diverticulum, he underwent segmental resection of the small intestine. Macroscopic examination revealed a diverticulum-like structure 2.5cm in size near the site of mesenteric attachment of the ileum. Histological examination showed diffuse and nodular proliferation of spindle cells positive for c-KIT and CD34 that had replaced the muscularis propria of the small intestine. Mutational analyses of the lesions revealed monoclonality of proliferating cells with a somatic mutation in c-kit exon 11 (p.Leu576Pro). Gut-wall replacing type of GIST should be recognized as a specific type of GIST causing diverticulum-like structures of the gastrointestinal tract.

Bilateral diffuse pseudoangiomatous stromal hyperplasia (PASH) causing gigantomastia in a 33-year-old pregnant woman: case report

Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferation of mammary stroma mostly described as incidental microscopic finding. It can clinically manifest as a palpable, well circumscribed breast mass or in rare cases as a diffuse bilateral process causing massive breast enlargement. The most postulated theory for aetiology of this condition is hormonal stimulation of mammary miofibroblast, particularly by progesterone. The definite diagnosis of PASH is based on typical pathological findings like stromal hyperplasia and empty slitlike channels positive for myofibroblastic and negative for endothelial markers. The main clinical differential diagnosis is a fibroadedoma or phylloid tumour and histologically a low grade angiosarcoma. There are less than 200 cases of tumorous PASH and less than 20 of diffuse PASH reported so far. Here we present a case report of huge diffuse PASH, that is, to our knowledge, first one in a pregnant woman.

Adrenocortical tumor in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Adrenocortical tumour have been described in patients with 21-hydroxylase deficiency. These tumours are usually considered to be ACTH – dependent, as diffuse adrenal cortical hyperplasia is commonly seen. We report adrenal cortical tissue tumours developed in three patients with untreated congenital adrenal hyperplasia due to 21-hydroxylase deficiency. All of them had symptoms of adrenogenital vililizing syndrome. A diagnosis of adrenocortical tumour was established by the symptoms, hormonal profile, ultrasonography, and adrenal CT scan. Two of the tumours were located in the right side, all the patients were performed surgery before hormonal replacement therapy because of evidence of secreated adrenal tumors, and the histological diagnosis indicated an adrenocortical adenoma. After removal of tumours, the size of adrenal gland was monitored by serial ultrasonography, and the congenital adrenal hyperplasia was confirmed by extremely high levels of basal serum testosterone, 17-OHP levels, increasing virilizing syndrome after surgery, diffuse hyperplasia of adrenal gland and identified mutations in CYP21A2 gene.

A Randomized Trial of External Stenting for Saphenous Vein Grafts in Coronary Artery Bypass Grafting

External stents inhibit saphenous vein graft (SVG) intimal hyperplasia in animal studies. We investigated whether external stenting inhibits SVG diffuse intimal hyperplasia 1 year after coronary artery bypass graft surgery. Thirty patients with multivessel disease undergoing coronary artery bypass graft surgery were enrolled. In addition to an internal mammary artery graft, each patient received one external stent to a single SVG randomly allocated to either the right or left coronary territories; and one or more nonstented SVG served as the control. Graft patency was confirmed at the end of surgery in all patients. The primary endpoint was SVG intimal hyperplasia (mean area) assessed by intravascular ultrasonography at 1 year. Secondary endpoints were SVG failure, ectasia (>50% initial diameter), and overall uniformity as judged by Fitzgibbon classification. One-year follow-up angiography was completed in 29 patients (96.6%). All internal mammary artery grafts were patent. Overall SVG failure rates did not differ significantly between the two groups (30% stented versus 28.2% nonstented SVG, p= 0.55). The SVG mean intimal hyperplasia area, assessed in 43 SVGs, was significantly reduced in the stented group (4.37 ± 1.40 mm(2)) versus nonstented group (5.12 ± 1.35 mm(2), p= 0.04). In addition, stented SVGs demonstrated marginally significant improvement in lumen uniformity (p= 0.08) and less ectasia (6.7% versus 28.2%, p= 0.05). There was some evidence that ligation of side branches with metallic clips increased SVG failure in the stented group. External stenting has the potential to improve SVG lumen uniformity and reduce diffuse intimal hyperplasia 1 year after coronary artery bypass graft surgery.

Chronic Toxicity and Carcinogenicity Studies of the Long-Acting GLP-1 Receptor Agonist Dulaglutide in Rodents.

The tumorigenic potential of dulaglutide was evaluated in rats and transgenic mice. Rats were injected sc twice weekly for 93 weeks with dulaglutide 0, 0.05, 0.5, 1.5, or 5 mg/kg corresponding to 0, 0.5, 7, 20, and 58 times, respectively, the maximum recommended human dose based on plasma area under the curve. Transgenic mice were dosed sc twice weekly with dulaglutide 0, 0.3, 1, or 3 mg/kg for 26 weeks. Dulaglutide effects were limited to the thyroid C-cells. In rats, diffuse C-cell hyperplasia and adenomas were statistically increased at 0.5 mg/kg or greater (P ≤ .01 at 5 mg/kg), and C-cell carcinomas were numerically increased at 5 mg/kg. Focal C-cell hyperplasia was higher compared with controls in females given 0.5, 1.5, and 5 mg/kg. In transgenic mice, no dulaglutide-related C-cell hyperplasia or neoplasia was observed at any dose; however, minimal cytoplasmic hypertrophy of C cells was observed in all dulaglutide groups. Systemic exposures decreased over time in mice, possibly due to an antidrug antibody response. In a 52-week study designed to quantitate C-cell mass and plasma calcitonin responses, rats received twice-weekly sc injections of dulaglutide 0 or 5 mg/kg. Dulaglutide increased focal C-cell hyperplasia; however, quantitative increases in C-cell mass did not occur. Consistent with the lack of morphometric changes in C-cell mass, dulaglutide did not affect the incidence of diffuse C-cell hyperplasia or basal or calcium-stimulated plasma calcitonin, suggesting that diffuse increases in C-cell mass did not occur during the initial 52 weeks of the rat carcinogenicity study.

Successful living-donor liver transplantation after treatment of sinus aspergillosis by endoscopic mycetoma removal and sinus drainage

A 47-year-old female was admitted to our hospital for treatment of end-stage liver disease due to primary biliary cirrhosis. Preoperative routine nasal sinus magnetic resonance imaging revealed diffuse inflammatory mucosal hyperplasia of the right maxillary sinus and mycetoma without invasive fungal sinusitis. Aspergillus antigen was positive. With a diagnosis of sinus aspergillosis, endoscopic sinus drainage and removal of mycetoma were performed. After endoscopic treatment, the right maxillary sinus was irrigated using amphotericin B for 2 weeks and then treated by iodine with gentamicin and ketoconazole for 6 weeks. At 1 month after endoscopic treatment, the mycetoma had disappeared. At 3 months after the endoscopic treatment, the patient underwent living-donor liver transplantation using the left and caudate lobe of her daughter. The patient made a satisfactory recovery and was discharged on 19 days after transplant. As of 44 months after transplant, she remains well without recurrence of aspergillosis.

Brunner's glands hyperplasia: diagnosis with EUS-FNA for suspected pancreatic tumor involving the duodenum.

Brunner's gland hyperplasia is a rare, benign, proliferative disorder of the duodenum. Large masses may cause obstructive and compressive symptoms which may depend upon the location of the tumour. Owing to its rarity, these lesions can be mistaken for malignancy on radiological and endoscopic examinations. Symptomatic Brunner's gland hyperplasia associated with pancreatitis is very rare and the literature is limited to a few case reports endoscopic ultrasound may be useful to obtain a correct diagnosis. We describe an unusual case of diffuse Brunner's gland hyperplasia of duodenum mimicking a malignancy involving the pancreas, in which EUS-FNA avoided a possible major surgery. Brunner's gland hyperplasia imaging is very similar to malignant pancreatic mass; EUS with FNA is mandatory to reach a correct diagnosis, avoiding surgery.

The Clinical Course of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

Current understanding of the clinical course of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is poor and based predominantly on small case series. In our clinical experience, we have found that the diagnosis of DIPNECH is frequently delayed because respiratory symptoms are ascribed to other lung conditions. The objectives of this study were to collect and analyze longitudinal clinical data on pulmonary physiology, chest high-resolution CT (HRCT) imaging, and therapies to better delineate the course of disease. We established a cohort of patients (N = 30) with DIPNECH seen at our institution. We used descriptive statistics to summarize cohort characteristics and longitudinal analytic techniques to model FEV1 % predicted (FEV1%) over time. All subjects were women who presented with long-standing cough and dyspnea. The majority had an FEV1% < 50% at the time of diagnosis. Forty percent were given a diagnosis of asthma as the cause for physiologic obstruction. The mean FEV1% for the entire cohort showed no statistically significant decline over time, but 26% of the subjects experienced a 10% decline in FEV1 within 2 years. Among the pathology samples available for review, 28% (five of 18) had typical carcinoids and 44% had associated constrictive bronchiolitis. We propose clinical diagnostic criteria for DIPNECH that incorporate demographic, pulmonary physiology, HRCT imaging, and transbronchial and surgical lung biopsy data. DIPNECH is a female-predominant lung disease manifested by dyspnea and cough, physiologic obstruction, and nodules on HRCT imaging. Additional research is needed to understand the natural history of this disease and validate the proposed diagnostic criteria.

Hyperthyroidism As a Complication Following Myloablative Therapy and Stem Cell Transplantation for Childhood Diseases

Thyroid dysfunction is a known complication following hematopoietic stem cell transplantation (HSCT) in children. Most reports in children describe hypothyroidism related to pre-transplant conditioning regimens, especially total body irradiation (TBI). We now report the development of post-transplant thyroid dysfunction on 8 children that developed hyperthyroidism following HSCT. Three patients were transplanted for metabolic diseases (two with Sanfilippo Syndrome and one with Adrenal Leukodystrophy, one for Acute Myelogenous Leukemia, one for Kostman’s Syndrome, one for Purine Nucleotide Phosphorylase Deficiency (PNP), one for Paroxysmal Nocturnal Hemoglobinuria (PNH) and one for Chronic Granulomatous Disease (CGD). Five children were transplanted with Unrelated Umbilical Cord Blood (URCB), one with matched sibling transplant and two with adult Matched Unrelated Donor (MUD) transplant. Four of the five patients receiving cord blood transplants received myloablative therapy with Busulfan, Cytoxan and ATG; one of the URCB patients and one MUD transplant patient received Fludarabine, Busulfan, Cytoxan and ATG and the other MUD transplant received Fludarabine, Cytoxan and two doses of TBI for conditioning. The patient that received the matched sibling transplant was prepared for transplant with Busulfan and Melphalan. The onset of hyperthyroidism ranged between 9 months and 5 years post transplant. Five patients were off of immunosuppression when hyperthyroidism was diagnosed and 2 were being treated for chronic GvHD; one with Etanercept, Cyclosporine and Solumedrol and one with Orapred and Imuran. One patient was still on prophylactic Tacrolimus when hyperthyroidism was diagnosed 9 months after transplant. All patients required a form of ablative therapy. Two received radioactive iodine as treatment. Three patients received Methimazole alone. One patient failed Methimazole, received radioactive iodine and then underwent thyroidectomy revealing follicular carcinoma. One of the patients did not receive any therapy; he had Hoshimoto’s thyroidits and went on to develop hypothyroidism. Another patient had a total thyroidectomy that revealed diffuse hyperplasia. All patients are surviving 1 to 9 years after diagnosis of thyroid disease.

Outcome of surgical treatment of primary aldosteronism.

The aim of this retrospective study was to analyze the early and long-term outcomes of the surgical treatment of primary aldosteronism (PA), the most common surgically correctable cause of endocrine hypertension. Serum Potassium levels, blood pressure values, and aldosterone/renin ratio (ARR) were assessed in 128 patients undergoing unilateral adrenalectomy for PA, before and after surgery. The role of lateralizing techniques and the relationship between outcome and histopathology findings were also evaluated. Biochemical cure of PA (ARR and kalemia normalization) was achieved in 95 % of patients, at early follow-up. Single aldosterone-producing adenoma, multinodular hyperplasia, and diffuse hyperplasia were found in 46, 45, and 9 % of the patients, respectively. No relationship between histopathology and persistence or recurrence of PA was found. The use of further lateralizing techniques in addition to computed tomography or magnetic resonance was the main predictor of PA cure (p = 0.02); adrenal venous sampling (AVS) was more accurate than scintigraphy in PA lateralization (p < 0.05). After surgery, hypertension was cured in 55 % and improved in 36 % of patients. Female gender, a lower number of antihypertensive drugs, and a shorter duration of hypertension were the main predictors of hypertension cure. At long-term, recurrent PA occurred in 3.7 % of cases. Early diagnosis and correct lateralization of hyperaldosteronism by means of AVS are keys to achieve surgical cure of PA and PA-related hypertension. PA may be also caused by unilateral hyperplasia, which may be cured by unilateral adrenalectomy. Recurrences of PA are rare, although a prolonged follow-up is required.

Nesidioblastosis (diagnosis, surgical treatment)

Nesidioblastosis (NB) is rare disease with organic hyperinsulinism syndrome and caused by diffuse hyperplasia and/or hypertrophy of pancreatic islands of Langerhans. The results of surgical treatment of 3 patients with NB are presented. In all patients the diagnosis was suspected at the preoperative stage and confirmed by histological examination later. Herewith in 2 patients NB was combined with insulinoma. All patients underwent corpora-caudal pancreatectomy. In postoperative period one patient hadn't episodes of hypoglycemia for the entire follow-up period (5 months), in another patient hypoglycemic states occurred at 1.5 months after surgery. The third patient required pancreatic head extirpation at 11 days after surgery due to persistent severe course of organic hyperinsulinism. In immediate postoperative period in the same patient hyperinsular hypoglycemia was observed that pointed on extrapancreatic source of insulin secretion. However contrast-enhanced CT did not reveal any formations. Thus, corpora-caudal pancreatectomy is preferable as surgical treatment. Results of surgical management can provide a complete regression of the symptoms, but do not guarantee absence of recurrence and even any changes in frequency and severity of hypoglycemic states.

Colorectal microcarcinoids in association with long-term exposure to urinary content: a case report and review of the literature.

Long-term exposure of colonic mucosa to urinary content and its association with increased risk of infection, mechanical and biochemical irritation, and malignancy have been described in the literature. Existing case reports and studies depict the low but distinct risk of malignancy in gastrointestinal segments which come in contact with urinary content as a result of surgical correction of urinary tract abnormalities. However, these reports are largely limited to colonic adenocarcinoma and urothelial cell carcinoma. Late urointestinal carcinoma in patients with ileal incorporation into the urinary tract has also been reported. To the best of our knowledge, however, there is only one case report documenting neuroendocrine (NE) cell hyperplasia in colonic mucosa after long-term cystoplasty. Our case is the first to describe microcarcinoids and diffuse NE hyperplasia occurring in a patient with congenital anorectal anomalies, resulting in long-term exposure of colonic mucosa to fecal stream and urinary content. This case, in conjunction with the reported cases in the literature, raises the distinct possibility of an association between exposure of colonic mucosa to urine and long-term development of malignancy, including NE neoplasms.

Thyroid Hemiagenesis Associated with Hyperthyroidism.

Thyroid hemiagenesis (TH), very rare congenital anomaly, is generally asymptomatic. We report two cases of TH with hyperthyroidism. Case One. The patient presented with signs and symptoms of thyrotoxicosis. Physical examination revealed asymmetric nodular goitre at right lobe. Biochemical analysis revealed the diagnosis of hyperthyroidism. Ultrasound showed multinodular hypertrophy in the right lobe and absence of the left lobe. Nuclear scan, confirming absence of the left lobe, showed hot nodules in the right one. The diagnosis was toxic multinodular goitre. Case Two. The thyroid was not palpable in this patient presented with signs and symptoms of thyrotoxicosis. Biochemical analysis revealed the diagnosis of autoimmune thyrotoxicosis. Ultrasound showed mild diffuse hyperplasia of the right lobe and agenesis of the left lobe. Nuclear scan, confirming absence of the left lobe, showed increasing diffuse uptake of radiotracer in the right one. The diagnosis was Graves' disease in this patient. After antithyroid medication, the patients were surgically treated with total excision of the thyroid tissue. TH is sometimes associated with disorders of the thyroid. Hyperthyroidism makes TH cases symptomatic. During evaluation of patients, ultrasound and nuclear scan usually report agenesis of one lobe and establish the diagnosis of TH. The surgical treatment is total removal of hyperactive tissue and total excision of the remaining lobe.

Prostate hyperplasia caused by long‐term obesity is characterized by high deposition of extracellular matrix and increased content of MMP‐9 and VEGF

Recent studies have shown a positive association of cancer and obesity, but the morphological and molecular mechanisms involved in this relationship are still unknown. This study analysed the impact of long-term obesity on rat prostate, focusing on stromal changes. Male adult Wistar rats were treated with high-fat diet to induce obesity, while the control group received a balanced diet. After 30 weeks of feeding, the ventral prostate was analysed by immunohistochemistry for cell proliferation, smooth muscle α-actin, vimentin, chondroitin sulphate and metalloproteinases (MMP-2 and 9). The content of androgen receptor (AR), oestrogen receptors (ERs) and vascular endothelial growth factor (VEGF) was measured by Western blotting, and activity of catalase and Glutathione-S-Transferase (GST) were quantified by enzymatic assay. Long-term obesity decreased testosterone plasma levels by 70% and resulted in stromal prostate hyperplasia, as evidenced by increased collagen fibres. Such stromal hyperplasia was associated with increased number of blood vessels and raised VEGF content, and increased expression of chondroitin sulphate, vimentin, α-actin and MMP-9. In spite of the high cell density in prostate, the proliferative activity was lower in the prostates of obese rats, indicating that hyperplasia was established during the early phases in this obesity model. AR levels increased significantly, whereas the ERα decreased in this group. Moreover, the levels of catalase and GST were changed considerably. These findings indicate that long-term obesity, besides disturbing the antioxidant control, causes intense stromal remodelling and release of factors that create an environment that can promote proliferative disorders in the gland, culminating with diffuse hyperplasia.

Pathology and diagnosis of proliferative and ulcerative dermatitis associated with Tunga penetrans infestation in cattle.

Tunga penetrans is the smallest biting flea known. In cattle, infestation by T. penetrans (tungiasis) typically affects the skin of the distal legs, udder, prepuce, and perianal area. A detailed clinical and pathologic description of bovine tungiasis, together with electron microscopy and molecular diagnostics to establish the identity of the parasite are described. Ninety percent of the cows and heifers and 80% of the bulls in a herd in northwest Argentina had proliferative and ulcerative skin lesions affecting the coronary band, interdigital space, heels, and rudimentary toes of the fore and/or rear limbs, teats, and/or prepuce. These proliferative lesions had multiple large cavities filled with hemorrhagic fluid, necrotic debris, and Tunga spp. parasites. Histologically, the skin showed diffuse papillary epithelial hyperplasia with severe orthokeratotic hyperkeratosis, and it was multifocally ulcerated and inflamed. Multifocally, sections of arthropod parasites were observed embedded in the epidermis and dermis with the posterior end toward the surface. Images of wet mounts and scanning electron microscopy of the parasite showed morphologic characteristics compatible with Tunga spp. Polymerase chain reaction followed by sequencing of the cytochrome c oxidase subunit II and the internal transcribed spacer region indicated 99% homology to published T. penetrans sequences. Tungiasis should be considered as a differential diagnosis for proliferative lesions in skin of cattle.

Imaging appearances of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia

ObjectiveThe objective of the study was to describe the imaging appearances of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) on computed tomography (CT). Materials and methodsElectronic medical records were searched for patients with pathology-proven DIPNECH who had a CT available for review. Eleven patients were included. ResultsThe most common finding on CT was small pulmonary nodules which were present in all patients and were multiple (≥5) in 7/11 patients. Other CT findings included mosaic pattern attenuation and bronchial wall thickening/bronchiectasis. ConclusionDIPNECH should be considered as a diagnostic possibility when multiple small pulmonary nodules are identified on CT, particularly if there is an associated carcinoid tumor.

Thyroid carcinoma in patients with Graves' disease: an institutional experience.

Graves' disease (GD) is an autoimmune disorder characterized by diffuse hyperplasia and excessive production of thyroid hormone. The association between thyroid carcinoma and GD is controversial. The prevalence of thyroid carcinoma was investigated in patients with GD who underwent thyroidectomy for thyroid nodular lesions or GD from 1994 to 2013 at our institution. Three hundred and forty-seven patients were placed into two groups: Graves' disease with nodular lesions group (group GN) included 85 patients who had thyroidectomy for nodular lesion, and Graves' disease group (group G) included 262 patients who had thyroidectomy for hyperthyroidism. There were 59 patients with thyroid carcinomas in the 85 patients (69 %) of group GN, including 3 follicular carcinomas (5 %), 1 poorly differentiated carcinoma (2 %), and 55 papillary thyroid carcinomas (93 %). Among the 55 papillary thyroid carcinomas, 19 cases were papillary thyroid microcarcinomas (34 %); and 5 cases of tall cell variant (9 %) were identified. There were 8 cases with lymph node metastasis (14 %), 6 cases with lymphovascular invasion (10 %), and 12 cases with extrathyroidal invasion (20 %). In addition, 24 carcinomas showed multiple foci of tumor (41 %). In contrast, 51 patients (19 %) of 262 patients in group G had carcinoma, including 2 follicular carcinomas (4 %) and 49 papillary thyroid carcinomas (96 %). In the 49 cases of papillary thyroid carcinomas, 47 cases were microcarcinomas (96 %); and 2 cases of tall cell variant (4 %) were found. There were no lymph node metastasis or lymphovascular and extrathyroidal invasion, but 11 cases (22 %) demonstrated multiple carcinoma foci. In conclusion, thyroid nodular lesions in patients with GD should raise a high suspicion of carcinoma, and these lesions are frequently clinically significant tumors. Incidental thyroid carcinomas in patients with GD are not uncommon, but most of them are low-risk papillary thyroid microcarcinoma without lymph node metastasis or lymphovascular and extrathyroidal invasion.

Losartan ameliorates “upstream” pulmonary vein vasculopathy in a piglet model of pulmonary vein stenosis

Pulmonary vein stenosis (PVS) is a relentless disease with a poor prognosis. Although surgical repair can effectively treat "downstream" (near left atrial junction) PVS, residual "upstream" (deep in lung parenchyma) PVS commonly dictates long-term survival. Our initial studies revealed an association between PVS and transforming growth factor-β signaling, which led us to investigate the effect of losartan on upstream pulmonary vein vasculopathy in a piglet model of PVS. Neonatal Yorkshire piglets underwent sham surgical banding (sham, n = 6), staged bilateral pulmonary vein banding of all pulmonary veins except the right middle pulmonary vein (banded, n = 6), and staged pulmonary vein banding with losartan treatment (losartan, 1 mg/kg/d, n = 7). After 7 weeks, the hemodynamic data were obtained and the piglets killed. Pulmonary vein banding (compared with sham) was associated with continuous turbulent flow in banded pulmonary veins, pulmonary hypertension (pulmonary artery/systemic blood pressure ratio 0.51 ± 0.06 vs 0.23 ± 0.02, P < .001), and diffuse pulmonary vein intimal hyperplasia in the upstream pulmonary veins (P < .001). Losartan administration decreased the pulmonary artery/systemic blood pressure ratios compared with those in the banded piglets (0.36 ± 0.08 vs 0.51 ± 0.06, P = .007) but it remained greater than those in the sham group (P = .001). Losartan was also associated with diminished pulmonary vein intimal hyperplasia compared with that in the banded piglets (P < .001) but still remained more than that in the sham group (P = .035). Pulmonary vein banding reduced vascular endothelial-cadherin expression, indicative of diminished endothelial integrity, which was restored with losartan. Losartan treatment improved PVS-associated pulmonary hypertension and intimal hyperplasia and might be a beneficial prophylactic therapy for patients at high risk of developing PVS after pulmonary vein surgery.

Pseudoneoplastic glandular lesions of the uterine cervix: a selective review.

Pseudoneoplastic glandular lesions of the cervix continue to be diagnostically challenging for the surgical pathologist. This review covers a select number of these lesions that may be misinterpreted as premalignant or malignant, with an emphasis on those about which Dr Scully has advanced our knowledge. The topics covered include microglandular hyperplasia, mesonephric hyperplasia, diffuse laminar endocervical glandular hyperplasia, lobular endocervical glandular hyperplasia, and endocervical adenomyoma. The first listed entity has a greater diversity of morphology than the name might imply including, but not limited to solid growth and prominent hyaline stroma. The second entity may be remarkably diffuse within the cervical wall and reasonably result in consideration of diagnoses such as minimal deviation adenocarcinoma (adenoma malignum), but has nonmucinous epithelium and bland cytology. The third entity, one of the least common of those considered, represents a peculiar form of reactive hyperplasia of the endocervical epithelium. The fourth entity is the one about which knowledge is still fast advancing. In pure form with no atypia it is almost certainly a clinically benign process, but a subset of cases show cytologic atypia and an occasional association with adenocarcinoma is seen. Finally, adenomyomas of the uterus in general have received much attention in recent years, mostly in the corpus, but the less common endocervical variant may be particularly problematic because mucinous epithelium in abundant myogenic stroma may be potentially confused with an infiltrating differentiated mucinous adenocarcinoma. Although immunohistochemistry may play a role on occasion in evaluating benign endocervical glandular proliferations the mainstay of their interpretation remains conventional morphologic analysis of routinely stained slides.