Aggressive maxillary squamous odontogenic tumour in a child: histological dilemma and adaptative surgical behaviour.

A case of a maxillary osteolytic tumour is described in a 9-year-old boy. Histological analysis led to an initial diagnosis of benign squamous odontogenic tumour, although this was not straightforward due to swelling, and cellular pseudo-malignant and non-specific signs. Because of the young age of the patient, a local surgical tumourectomy was first chosen with respect to the mixed dentition. For 10 months, the evolution was satisfactory. Then, a very aggressive tumoural recurrence with lip and palate infiltration led to doubts as to the histologic nature of the tumour. Efficient collaboration between several specialized pathologist teams finally confirmed that this was a squamous odontogenic tumour but in a very aggressive form. Radical surgery was then carried out.

Ductal cyst formation in collagen-embedded adult human islet preparations. A means to the reproduction of nesidioblastosis in vitro.

Neogenesis of endocrine islets from ductal epithelium termed nesidioblastosis has been described in vivo after various experimental conditions (90% pancreatectomy or pancreas wrapping in the rodent) and in clinical pathologies. In the adult regenerating pancreas, a proliferation and organization of ductal epithelium into tubular structures precedes its differentiation into endocrine cells. Reproduction of nesidioblastosis in vitro may provide a novel approach to human islet propagation in vitro. With this aim, adult human islet preparations were cultured in diverse three-dimensional (3D) gels in the presence of serum. After 3-5 days in rat tail collagen gels, proliferating (bromodeoxyuridine-positive) cystic structures appeared associated with islets and as isolated spheres. Percentage labeling indexes of the cysts were 4.1, 18.7, 15.4, and 13.3% after 3, 5, 7, and 10 days of culture, respectively. Immunohistochemistry confirmed the ductal (carbohydrate antigen 19-9) and epithelial (keratin-1) nature of the cysts. No cysts were formed in agarose gels or Vitrogen 100, whereas the cyst number was increased by the quantity of serum (20% > 10%) and gels rich in extracellular matrix components and growth factors (Matrigel). The latter lead to tubular networks. Single endocrine islet cells were observed in the ductal cysts after 7 (2.8%) to 10 (5.6%) days in rat tail collagen. Our observations paralleled the changes characteristic of the regenerating pancreas in vivo. 3D culture may permit the identification of matrix and media constituents promoting the neogenesis of islets and may be the means to increase the mass of endocrine tissue obtained from adult cadaveric pancreases for transplantation.

Adult human cytokeratin 19-positive cells reexpress insulin promoter factor 1 in vitro: further evidence for pluripotent pancreatic stem cells in humans.

Human pancreatic cells with a typical ductal phenotype and potential to proliferate can be obtained in vitro, but the differentiation capacity of these putative human pancreatic stem cells remains to be documented. We investigated the protein and mRNA expression of insulin promoter factor 1 (IPF-1) (or pancreas/duodenal homeobox 1), a transcription factor critical for pancreatic development and endocrine cell neogenesis, in human pancreatic ductal cells derived from cultured exocrine tissue. In vitro, exocrine cells rapidly adhered (within 12 h) and were de-/transdifferentiated to ductal cells after 3 days with a dramatic loss of amylase protein (n = 4, 92 +/- 3.3%, P < 0.05 vs. day 1) and a simultaneous increase of ductal cytokeratin 19 protein (n = 4, 3.4-fold on day 3 and 7-fold on day 9, P < 0.05 vs. day 1). IPF-1 protein and mRNA levels were low to undetectable in exocrine preparations before culture. After 2 days of culture, a 3.2-fold increase in IPF-1 protein was observed, corresponding to the characteristic 46-kDa protein in Western blots. Reverse transcriptase-polymerase chain reaction confirmed a 10.5-fold increase in IPF-1 mRNA levels after 3 days of culture (n = 5, P < 0.001 vs. day 1). Double immunocytochemistry showed direct evidence that IPF-1 appeared during culture in these exocrine-derived ductal cells (cytokeratin 7-positive) and was not merely in contaminating endocrine cells (chromogranin A-positive). In conclusion, we describe herein the first converging evidence on both the molecular and protein level that human cells with a typical ductal phenotype derived ex vivo from pancreatic exocrine tissue (obtained from healthy donors) can reexpress IPF-1 in culture, suggesting their pancreatic precursor/stem cell potential.

A novel 9-base pair duplication in RET exon 8 in familial medullary thyroid carcinoma.

Familial medullary thyroid carcinoma (FMTC) and multiple endocrine neoplasia type 2A syndromes are dominantly inherited diseases caused by activating germline mutations of the RET protooncogene. The majority of these patients carry a germline point mutation affecting one of five cysteine residues encoded by exon 10 (codon 609, 611, 618, or 620) or 11 (codon 634). In a few FMTC families, point mutations involving noncysteine codons in exon 13 (codons 768, 790, and 791), 14 (codon 804), or 15 (codon 891) have been reported. Hirschsprung's disease is a nonneoplastic disorder associated with RET mutations leading to a loss of function effect. Mutations are identified in 50% of the familial cases and are scattered along the gene. We now report the study of a FMTC family with four affected members and a history of fatal neonatal intestinal obstruction in the sister of the proband. Genetic analysis demonstrated the absence of an usual FMTC mutation and the presence of a germline 9-bp duplication in RET exon 8 in the heterozygous state in all patients with MTC. This new mutation creates an additional cysteine residue in the extracellular cysteine-rich domain of RET. Further studies are warranted to confirm whether this new mutation is causing MTC only or could be associated with Hirschsprung's disease.

Negative immunohistochemical detection of CD103 (alphaEbeta7 integrin) in the infiltrates of acute rejection in liver and kidney transplantation.

BACKGROUND: The infiltration of epithelium by CD8+ T lymphocytes in human renal or liver allografts is a critical feature of acute rejection. CD103 expression can be acquired in vitro by CD8+ cytotoxic T lymphocytes in response to allogeneic renal epithelial cells and promotes their adhesion to epithelium and subsequent lysis of epithelial cells. We investigated the expression of CD103 in T-cell infiltrates during acute renal or liver rejection (grade < III). METHODS: Immunohistochemical detection of CD103 in 11 liver and 10 kidney transplant biopsies with histopathological diagnosis of acute rejection. RESULTS: None of the infiltrates expressed detectable CD103, although positive controls were stained under our conditions. CONCLUSIONS: Failure to detect CD103 in renal biopsies can be related to the early posttransplantation interval (<6 months) corresponding to a first rejection episode. In our hands, immunohistological detection of CD103 was not possible in the infiltrates of acute rejection in liver or kidney transplantation.

Medullary thyroid microcarcinoma: a clinicopathologic retrospective study of 38 patients with no prior familial disease.

Thirty-eight patients (25 women, 13 men; mean age, 57.8 [32 to 91]) showing one or more medullary thyroid microcarcinomas (ie, < 1 cm), with no prior MEN II or medullary thyroid carcinoma history in their family, were reviewed. Follow-up was available for 29 patients (mean, 53.6 months [1 to 147]). 21 patients (72.4%) are alive and free of disease, four patients (13.8%) died during follow-up without disease, 2 patients are alive with disease (local recurrence and persistent hypercalcitoninemia) after 80 and 99 months, respectively, and 2 patients died of disease after 24 and 46 months. Most tumors were incidental pathological findings (19 of 38) or were discovered by systematic blood calcitonin measurement for a nodular thyroid disease (15 of 38). Only the four patients who had an unfavorable outcome were symptomatic cases (palpable micro-MTC, diarrhea, cervical lymph node metastasis and pulmonary metastatic disease). The two patients with metastatic disease at diagnosis died during follow-up. In univariate analysis, a symptomatic medullary thyroid carcinoma was a strong predictor of an unfavourable outcome (p < .00008), as were the preoperative calcitonin level (P = .007) and an elevated postoperative calcitonin level (P = .004). Among 30 histopathological criteria, only the presence of amyloid correlated with an unfavorable outcome (P = .018).

Resection for advanced cancer of the thoracic esophagus: cervical or thoracic anastomosis? Late results of a prospective randomized study.

During a 2 1/2-year period, 60 consecutive patients with cancer of the thoracic esophagus were randomized to undergo a cervical or thoracic anastomosis. The tumors were staged postoperatively (stage I, n = 2; stage II, n = 19; stage III, n = 9; and stage IV, n = 30) and were almost equally distributed between the two groups. The upper limit of three tumors was above the convexity of the aortic arch. The esophageal specimens were studied with regard to measurements of the tumor and of the resected esophagus. The microscopic aspects were evaluated by serial sections after vital staining. The prevalence of ignored plurifocal cancers, of submucosal infiltrations, and of distant areas of dysplasia in both groups was confirmed. Malignant invasions of esophageal sections were more frequent in patients undergoing thoracic anastomosis (10 versus 3), and diseased upper mediastinal lymph nodes were more frequent in those undergoing cervical anastomosis (17 versus 7). Mortality was equally divided between the two groups. Respiratory complications and recurrent laryngeal trauma were more frequent in patients having cervical anastomosis. Long-term survivors had stage N0 disease, with a healthy esophageal section. Even though subtotal esophagectomy reduces the prevalence of microscopic esophageal wall invasion above the tumor and allows more complete unilateral exploration and resection of invaded lymph nodes, it offers no significant benefit concerning survival of patients with advanced cancer and malignant lymphadenopathy.

Why do frozen sections have limited value in encapsulated or minimally invasive follicular carcinoma of the thyroid?

The diagnosis of encapsulated or minimally invasive follicular carcinoma of the thyroid requires the proof of vascular or capsular invasion. The aim of the present study was to evaluate the relationship between intraoperative diagnosis (benign, suggestive of carcinoma, or malignant) and the final histopathologic criteria for encapsulated or minimally invasive follicular carcinoma (tumor size, capsular invasion, vascular invasion, and differentiation). This was a retrospective study of 63 cases of encapsulated or minimally invasive carcinomas, with the final histopathologic diagnosis taken as the "gold standard." The sensitivity of frozen sections for the diagnosis of malignant neoplasm was 17%. The median number of vascular invasions was 1, identified with a mean number of 9 paraffin-blocks of the tumor. In most cases, intraoperative frozen sections are unable to establish the proof of malignant neoplasm. Intraoperative study of tumor differentiation is useful to select follicular tumors that require a rapid definitive diagnosis and a completion thyroidectomy within 48 to 72 hours (73% of the cases in our study).

Multiglandular disease in seemingly sporadic primary hyperparathyroidism revisited: where are we in the early 1990s? A plea against unilateral parathyroid exploration.

BACKGROUND: Most of the available data on multiglandular disease (MGD) originate from long-term series. The spectrum of the disease has changed now because of earlier diagnosis. We decided to assess the current frequency of MGD in seemingly sporadic primary hyperparathyroidism. METHODS: MGD was defined as the finding that more than one grossly enlarged gland weighed more than 50 mg and the rim of normal parathyroid tissue was diagnostic of adenoma. Nine hundred eight consecutive neck explorations for hyperparathyroidism were performed, 624 before 1989 and 284 between 1989 and 1991, and studied retrospectively. Since 1989, oil Red O staining has been done to assess hyperfunction. RESULTS: When multiple endocrine neoplasia and non-multiple endocrine neoplasia familial cases of hyperparathyroidism are excluded, the frequency of MGD in seemingly sporadic primary hyperparathyroidism, 17.7% before 1989, is still 14% since then, including a 3% frequency of true multiple adenomas. With more restrictive criteria, which exclude the second enlarged gland if it weighed less than 100 mg, if it had no rim, and if oil Red O staining was negative, the frequency of MGD in sporadic hyperparathyroidism has remained 11% since 1989. Unilateral exploration had missed 78% of second enlarged glands, and preoperative imaging studies, when performed, showed more than one gland in only two of 22 cases. CONCLUSIONS: Routine bilateral neck exploration is recommended in primary hyperparathyroidism because of a current frequency of MGD of at least 11%.

Essential hypertension: first reason for persistent hypertension after unilateral adrenalectomy for primary aldosteronism?

BACKGROUND: Despite cure of primary aldosteronism by surgical resection, hypertension persists postoperatively in 30% to 50% of patients. The aim of this study was to determine factors influencing long-term outcome of blood pressure after unilateral adrenalectomy for primary aldosteronism. METHODS: Records of 100 patients who underwent unilateral adrenalectomy for primary aldosteronism from 1970 through 1997 were reviewed. Patients were distributed in 2 groups according to whether blood pressure was normal (criteria of World Health Organization). Clinical, biochemical, and pathologic data were compared. RESULTS: All patients were biochemically cured. Blood pressure was normal in 56 patients and improved in 44 (mean follow-up, 69 and 59 months). Persistent hypertension correlated with age, known duration and seriousness of preoperative hypertension, family history of hypertension, no preoperative response to spironolactone, and contralateral adrenal hypertrophy. Gender, surgical approach, and pathologic findings were not predictive factors of blood pressure outcome. The prevalence of hypertension was almost the same in these postoperative patients as the prevalence of essential hypertension in a random population of the same age. CONCLUSIONS: Early unilateral adrenalectomy allows cure or improvement of hypertension in all patients with primary aldosteronism induced by unilateral excessive source of aldosterone secretion regardless of the pathologic findings. Persistent hypertension suggests that coexisting essential hypertension is present.

Thyroid carcinomas involving follicular and parafollicular C cells: seventeen cases with characterization of RET oncogenic activation.

Recent studies have focused on the occurrence of concomitant medullary-papillary thyroid carcinomas (MTC-PTC). The aims of this report were to compare the frequency of occult PTC in a population with MTC versus a control population that had undergone thyroidectomies and to check whether differences could be related to particular phenotype or genotype. To achieve these goals, we determined the frequency of occult PTC among patients operated for MTC (n = 82) or undergoing total thyroidectomy mainly for goiter and/or nodules (n = 7313) between 1994-2001. We then examined the clinical, histologic, and genetic characteristics (using a bio-chemical family inquiry and screening for RET germline mutations) of patients with associated PTC-MTC. Results show a significantly higher frequency of occult PTC in MTC (14.7%) than in total thyroidectomy (6.8%; p < 0.01). Seventeen cases of MTC or bilateral C-cell hyperplasia (CCH) and separate occult PTC were identified from 16 different families. Although common RET mutations providing evidence of familial forms of MTC were identified in only 3 of 16 families, clinical and histologic features usually seen in inherited forms of MTC such as young age of occurrence, bilateral CCH or associated case in family were found in 11 of the remaining 14 patients. In conclusion, results suggest that the association of MTC-PTC is not only a coincidence. Surprisingly, 11 of 17 MTC-PTC patients exhibited clinical, histologic, and/or family features usually encountered in familial forms despite the fact that no RET defect were present. This suggests the possible involvement of another gene or uncommon abnormality of RET gene.

Aggressiveness and quantification of epithelial proliferation of middle ear cholesteatoma by MIB1.

OBJECTIVE: To assess an easy method that predicts cholesteatoma aggressiveness. STUDY DESIGN: An experimental prospective study. METHODS: Monoclonal antibody MIB1 was used to determine epithelium proliferation in 91 cholesteatomatous ears. Clinical and surgical parameters were compared with proliferation activity to determine pathological and clinical correlation. RESULTS: Statistical correlations were established between hyperproliferation of the cholesteatoma and severe bone erosion (leading to major cholesteatoma complications) and between hyperproliferation and middle ear inflammation (associated with more surgical difficulties and a higher risk of recurrence). A high proliferation index was also found in children's cholesteatoma, which is known to have more aggressive behavior. CONCLUSION: Immunohistochemical use of the MIB1 antibody is a simple technique that can help to determine the aggressiveness of a cholesteatoma.

Mixed ductal-endocrine carcinoma of the pancreas: a possible pathogenic mechanism for arrhythmogenic right ventricular cardiomyopathy.

We describe herein a case of a mixed ductal-endocrine pancreatic carcinoma. Rare cases of mixed pancreatic tumors have been described, with endocrine and exocrine components each making up a significant proportion of the neoplasm; to our knowledge, only one case has been reported with a mixed liver metastasis. In our case, ductal and endocrine cells were intimately admixed in the primary tumor and in a peripancreatic lymph node metastasis, diagnosed by standard light microscopy and double immunostaining for cytokeratin 19 and synaptophysin. The endocrine component was immunoreactive for somatostatin. Tumors with admixed endocrine and exocrine components support the hypothesis of a common endodermal histogenesis for the ductal and endocrine cells in the human pancreas.

[Malignant synovial "chondromatosis" or chondrosarcomatous transformation of synovial chondromatosis of the knee?]. / "Chondromatose" synoviale maligne d'emblée ou évolution chondrosarcomateuse d'une chondromatose synoviale du genou?

A case of chondrosarcoma of the knee with clinical and histopathological features of malignant chondromatosis in a 40-year-old white man is reported. Malignant transformation of true chondromatosis is uncommon and has important implication of diagnosis and surgical treatment.

[Atypical decubitus fibroplasia: a recent entity. Apropos of a case of an adolescent girl]. / La fibroplasie atypique de décubitus: une entité récente. A propos d'un cas chez une adolescente.

Atypical decubital fibroplasia (FAD) occurs especially in elderly and physically debilited or immobilized patients. We report one observation which is peculiar due to the patient's young age and its circumstances. The painless mass is situated in hyperpressure areas (shoulder, posterior or lateral chest wall, sacrum). The lesion is situated in the deep subcutis and has ill defined limits; it is characterized by zones of fibrinoid necrosis and fibrosis and a prominent myxoid stroma. The differential diagnoses includes mesenchymatous malignant tumors and non neoplastic fibroblastic proliferations such as proliferative fasciitis and decubitus ulcer. The prominent underlying factor and the initial event contributing to its pathogenesis seems to be ischemia. Although some recurrent cases have been reported, FAD is a benign lesion whose treatment is surgical removal.

[Gastric metastasis of a malignant melanoma of the choroid]. / Métastase gastrique d'un mélanome malin de la choroïde.

Gastric metastases of choroid malignant melanoma seem to be exceptional since less than 10 cases have been previously published. We report the case of a 71 year old patient with a gastric melanosarcoma secondary to a choroid malignant melanoma. Gastric metastasis was revealed by digestive bleeding occurring 18 years after right eye enucleation. Gastroscopy showed black ulcerated tumors. Histology confirmed the diagnosis portraying typical melanic pigments within the gastric mucosa. Laser photocoagulation of the gastric lesion was used for the first time in this indication. As a result, hemorrhage decreased and the patient's comfort was improved.

[Cholesterol embolism: unusual cause of small intestine occlusion]. / Embolie de cholestérol: une cause rare d'occlusion de l'intestin grêle.

We describe a case of small bowel obstruction secondary to cholesterol crystal embolism in a 83-year-old man. Clinical symptoms were dominated by weight loss and vomiting. Small bowel barrium X-ray displayed a short and unique stricture of the jejunum. Atheromatous embolism was suspected in the presence of an aortic aneurysm. At laparotomy, a 2 cm stricture of jejunum was identified and a 6 cm length segment of small bowel was resected. Pathological features were consistent with cholesterol crystal embolism. The patient did well 3 months after surgery. This observation points out the nonspecific clinical presentation of gastrointestinal cholesterol embolism.

[Lymphomas of the colon complicating hemorrhagic rectocolitis]. / Lymphomes du côlon compliquant une rectocolite hémorragique.

Colonic lymphoma is a rare complication of ulcerative colitis. We report two cases of B cell colonic lymphoma occurring in two patients who had a left-sided ulcerative colitis for 7 and 24 years respectively. The diagnosis was made during surgery in one case and at colonoscopy in the other. Complete remission was achieved after surgery and chemotherapy with a 8-year and 15-month follow-up respectively.

[Excluded rectum during Crohn's diseases: what is the risk of dysplasia?]. / Rectums exclus au cours de la maladie de Crohn: quel est le risque de dysplasie?

OBJECTIVES: An excluded rectum may be at risk of carcinoma in the course of Crohn's disease. Surveillance of patients requires detection of dysplasia. The aim of our study was to determine the frequency of dysplasia from secondary proctectomy specimens in active rectal Crohn's disease. METHODS: Twenty three patients (13 women and 10 men, median age 38 years) were studied. The median duration of rectal exclusion was four years. Detection of dysplasia relied upon histopathology. Immunohistochemistry with MIB-1 (Ki-67) and anti-p53 (clone DO7) antibodies was performed as well. RESULTS: Frequency of dysplasia was 30%. This was low grade dysplasia, focally observed in proctectomy specimens. MIB-1 was positive on 46% of dysplastic cells. There was no expression of p53 protein. CONCLUSIONS: These results must be taken into account for decision of secondary proctectomy, in patients having an excluded rectum for Crohn's disease, when ileorectal anastomosis is not possible. Rectal endoscopic surveillance is advisable with multiple biopsies according to focal distribution of dysplasia.

Paraneoplastic intestinal pseudo-obstruction as the presenting feature of small-cell lung cancer.

A previously healthy 50-year old man presented with acute small bowel obstruction. No etiology was found at laparotomy. Postoperatively, the patient remained symptomatic with nausea, vomiting and severe constipation. Gastroscopy revealed retained food in the stomach. Gastric emptying of solids and liquids was dramatically decreased at scintigraphy. The colon was dilated on X-ray study. Chest X-ray revealed a pneumopathy and a small-cell lung cancer was discovered at bronchoscopy. The patient died 5 months after onset. Histologic study of the gut showed widespread degeneration of the myenteric plexus with plasma cell infiltration, Schwann cell proliferation and a reduced number of neurons of which many were abnormal. Intestinal pseudo-obstruction can reveal a small-cell lung cancer; the mechanism of neuronal impairment leading to pseudo-obstruction remains unknown, but could be related to the pathophysiology of paraneoplastic syndromes.