Progastrin production transitions from Bmi1+/Prox1+ to Lgr5high cells during early intestinal tumorigenesis.

Progastrin is an unprocessed soluble peptide precursor with a well-described tumor-promoting role in colorectal cancer. It is expressed at small levels in the healthy intestinal mucosa, and its expression is enhanced at early stages of intestinal tumor development, with high levels of this peptide in hyperplastic intestinal polyps being associated with poor neoplasm-free survival in patients. Yet, the precise type of progastrin-producing cells in the healthy intestinal mucosa and in early adenomas remains unclear. Here, we used a combination of immunostaining, RNAscope labelling and retrospective analysis of single cell RNAseq results to demonstrate that progastrin is produced within intestinal crypts by a subset of Bmi1+/Prox1+/LGR5low endocrine cells, previously shown to act as replacement stem cells in case of mucosal injury. In contrast, our findings indicate that intestinal stem cells, specified by expression of the Wnt signaling target LGR5, become the main source of progastrin production in early mouse and human intestinal adenomas. Collectively our results suggest that the previously identified feed-forward mechanisms between progastrin and Wnt signaling is a hallmark of early neoplastic transformation in mouse and human colonic adenomas.

[The lymph node of Mondor: myth or reality?]. / Le ganglion de Mondor : mythe ou réalité ?

AIM OF THE STUDY: Lymph node involvement is one of the most significant prognostic factors of patients with rectal cancer. Despite major advances in our understanding of the propagation of the rectal cancer, the lymphatic drainage of the rectum remains unclear. This study was designed to assess the number of lymph nodes located around the superior rectal artery and to assess the frequency of Mondor's lymph nodes. PATIENTS AND METHODS: Twenty-five anatomic subjects were studied. All resections were performed using total mesorectal excision. Lymph nodes were sought in the tissue surrounding the superior rectal artery up to 2 cm under the ending of the superior rectal artery by manual dissection and were submitted for histological examination. The correlation between the number of lymph nodes, and the volume and weight of the tissue surrounding the superior rectal artery was evaluated by non-parametric Spearman test. RESULTS: The mean number of lymph nodes per specimen was 2.7 +/- 1.4. The size of the lymph nodes varied between 1 and 7 mm. The lymph nodes were mostly smaller than 3 mm (56%). The number of lymph nodes in the superior rectal mesentery was independent of its volume and its weight. Seven subjects had a Mondor's lymph node. The mean size of Mondor's lymph node was 3.4 +/- 2.1 cm. CONCLUSIONS: The number of NL located around the superior rectal artery is small, varying between 1 and 5. The Mondor's lymph node is an inconstant rectal NL. Its only characteristic is its location in the bifurcation or trifurcation of the superior rectal artery.

Dissociated overexpression of cathepsin D and estrogen receptor alpha in preinvasive mammary tumors.

The role of estrogen as a promoter agent of sporadic breast cancer has been considered by assaying, in benign breast disease (BBD) and in situ carcinomas (CIS), 2 markers, the estrogen receptor alpha (ERalpha) and cathepsin D (cath-D) involved in estrogen action on mammary tissue. ERalpha and cath-D were assayed by quantitative immunohistochemistry using an image analyzer in 170 lesions of varying histological risk (94 BBD and 76 CIS), and in "normal" glands close to these lesions. The ERalpha level increased significantly in proliferative BBD with atypia (P < .001), in non-high-grade CIS (P < .001), and in adjacent "normal" glands. ERalpha level was decreased in high-grade ductal CIS (DCIS) and also in adjacent "normal" glands. Cath-D level increased in ductal proliferative BBD (P < or = .01) and in high-grade DCIS (P < or = .003), but not in the other lesions. After menopause, ERalpha level was increased (P = .012) but not cath-D level. According to Mac Neman test, the high-grade DCIS were predominantly ERalpha negative and cath-D positive (P = .0017), and the other CIS were predominantly ERalpha positive and cath-D negative (P = .0002). The 2 markers are overexpressed early in premalignant lesions, but independently. This dissociation suggests a branched model of mammary carcinogenesis involving 1 estrogen-independent pathway with high cath-D and low ERalpha levels (including high-grade DCIS) and 1 estrogen-dependent pathway, with high ERalpha level (including proliferative BBD with atypia and low-grade DCIS). We propose that ERalpha-negative breast cancers may develop directly from high-grade DCIS and that ERalpha assay in preinvasive lesions should be considered in prevention trials with antiestrogens.

Small carcinomas of the pancreas with associated chronic pancreatitis: two case reports.

Two cases of pancreatitis associated with papillary atypical hyperplastic lesions and micro-invasive cancers are reported. They are interesting from an etiopathogenic and diagnostic point of view by again illustrating the problem of transmission between hyperplastic lesions and cancer, together with the difficulties encountered in asserting the certainty of diagnosis. In each observation the association of pancreatic lesions, of all stages of hyperplasia, and of cancer can be observed. This suggests that transmission occurs between those different lesions. In such cases diagnosis of benignity or malignancy is always difficult to assert. No clinical, biological, morphological or even cytological criterion allows one to make a ruling. For this reason excision is recommended by the authors whenever the etiology of pancreatitis remains obscure and especially in the presence of important dystrophic lesions.

Ultrasonic and histopathological correlations of deep focal hepatic lesions induced by stereotaxic Nd-YAG laser applications.

Thirty six deep focal hepatic lesions were induced in eleven piglets by means of an Nd-YAG laser. Laser shots of 80 W power and 10 s duration were used, the beam being transmitted through an echoguided stereotaxic handpiece. From day 0 to day 120, the animals underwent ultrasonographic and morphological controls. At lasering time an hyperechoic image--12-18 mm in diameter--appeared due to boiling of tissue water. During the twenty postoperative days the lesion core was an echo-free area due to tissue vaporization, surrounded by an hyperechoic ring of increasing fibrosis, containing neovascularization and biliary ductules, while the hypoechoic outer area represented the peripheral halo of edema. In the long term, hyperechoic structures--swollen fibrotic septa of homogeneous fibrotic network--invaded the lesion site confirming good healing.

[Undifferentiated small cell carcinoma and diffuse endocrine system (author's transl)]. / Epithélioma anaplasique à petites cellules et système endocrien diffus.

Oat cell carcinomas of the lung are sometimes associated with endocrine secretion. Resulting syndromes, first regarded as "paraneoplasic", are in fact imputable to secretory activity of the tumoral cells, as demonstrated by electron microscopy and immunofluorescence studies. Such ascertainments are explained by the existence in the bronchial tree of a diffuse endocrine system sector, from which carcinoid and oat cell carcinoma originate. However, the authors consider other histogenetic hypotheses and rapidly survey the extra-pulmonary oat cell carcinomas.

Primary sinusoidal lymphoma of the liver revealed by autoimmune hemolytic anemia.

Primary liver lymphomas usually present with the clinical picture of a liver tumor, and are characterized by a predominantly portal invasion by lymphoid cells of the B-cell phenotype. We report a case of primary sinusoidal lymphoma of the liver, in a 36 year-old male patient, revealed by homogeneous hepatosplenomegaly and infiltration of liver sinusoids by morphologically normal lymphocytes, without destruction of the parenchyma. Immunohistochemistry in paraffin-embedded tissue sections was positive for the pan T-cell marker MTI, weakly positive for UCHLI, and negative for CD3, and B-cell markers were negative; these findings were consistent with the diagnosis of T-cell lymphoma. The clinical, histological and immunological presentation of this lymphoma was similar to that of hepatosplenic gamma delta T-cell lymphoma. Autoimmune hemolytic anaemia preceded the lymphoma. Despite chemotherapy, the patient died 24 months after the initial presentation in the leukemic phase. A better understanding of this exceptional but characteristic entity is required for an accurate and early diagnosis.

[Neurologic involvement in malignant mid-face granuloma]. / Atteintes neurologiques dans les granulomes malins centro-faciaux.

We report 4 cases with neurological disorders due to lethal centrofacial granulomas of unknown origin, and we review the relevant literature. This puzzling disease is characterized by a relentless ulceration of the nose progressing toward the base of the skull, and frequently involving the cranial nerves, the meninges and later the central nervous system. The main clinical point in such situations is to ascertain that no microorganism, no cancer, no specific disease is responsible for the centrofacial lesions, since the microscopic findings may be non-specific. When the entire work-up to exclude all differential diagnoses is completed, the clinician has to deal with lethal centrofacial granuloma. This seems to be a heterogeneous disease, in most of the cases close to malignant T lymphomas. Management is based on radiotherapy, chemotherapy and renutrition with treatment of frequent infectious complications. The prognosis is poor.

[Cytometric profiles of DNA content in cervical intraepithelial neoplasia (CIN)]. / Profils cytométriques du contenu en ADN dans les néoplasies intra-épithéliales cervicales (CIN).

The cervical cytologic screening is responsible for the overall decline in the incidence of cervical cancer. Despite this apparent success, the cytologic assessment by light microscopy of cervical smear has recently been shown to have deficiencies particularly in cervical intraepithelial neoplasia (CIN). Now, this pathology of the uterine cervix is increasingly becoming recognized as a major health problem in young women because of its high frequency and its association with the development of cervical carcinoma. Flow cytometry (FCM) is widely used as a rapid method to analyse DNA content of a great number of cells on a cell by cell basis. The authors have applied FCM to CIN in order to reinforce the cytologic screening of cervical smears. Three abnormal DNA patterns have been observed: increased and heterogeneous DNA pattern; increased S and G2+M phases; abnormal DNA content. The statistical calculation has emphasized the significant relation linking these DNA patterns with the cytologic diagnosis and the severity of CIN. Therefore, FCM is a powerful complementary tool in cervical pathology.

[Portal hypertension and hypervitaminosis A. Apropos of 2 cases and review of the literature]. / Hypertension portale et hypervitaminose A. A propos de deux cas et revue de la littérature.

Portal hypertension consecutive to hypervitaminosis A has seldom been well documented. Two cases are reported here. The first case concerns a 39-year old woman who had taken meladinine (8-methoxypsoralen) for the purpose of tanning. In the second case, a 43-year old woman had absorbed Plethoryl (a combination of tiratricol, cyclovalone and retinol) in order to lose weight. Both patients had histological hepatic lesions, such as hypertrophic Ito cells, perisinusoidal cirrhosis and spontaneous autofluorescence, suggestive of vitamin A overload, associated with a hepatic vein pressure gradient of 10 mmHg or more and high liver concentrations of vitamin A. The responsibility of Plethoryl in case 2 is beyond any doubt, but the mechanism of hypervitaminosis in case 1 is controverted. A review of the literature has provided detailed information on the signs of vitamin A overload, the frequency of which is probably underestimated. Patients with portal hypertension of unknown origin should be investigated for hypervitaminosis A.

[Carcinoid tumor of the larynx. Ultrastructural and immunofluorescence study]. / Carcinoïde du Larynx. Etude ultrastructurale et immunofluorescence.

Report of a 54 year-old man with a carcinoid tumor in the larynx and cervical lymph node metastasis. This left sided and dum-bell shaped tumor was spreading from the vocal cord to the piriform sinus. It was smooth, reddish and rubbery. Microscopic study showed, near by the mucosa, the tumor cells arranged in a trabecular pattern, but more disseminated and infiltrating in the deepness. Grimelius stain was positive, Masson Fontana stain negative. Electron microscopy showed neuro-secretory type granules. Immuno-histo-chemical study revealed irregularly scattered cells which were positive for ACTH, but negative for somatostatin, calcitonin and gastrin. Review of literature for this extremely rare tumor.

[Morphological aspects of parathyroid hyperplasia in patients with chronic renal insufficiency on dialysis]. / Aspects morphologiques de l'hyperplasie parathyroïdienne des insuffisants rénaux chroniques dialysés.

The authors present an anatomic study of parathyroid hyperplasia in 15 patients presenting chronic renal failure treated by hemodialysis (mean time 6 years). The light microscopic examination (n = 56) confirms diffuse hyperplasia so occur in patients submitted to dialysis for a period inferior to 4 years while nodular hyperplasia occurs in patients submitted to dialysis for longer a time. Mixed hyperplasia may be considered a transitional form between diffuse and nodular hyperplasia. Electron microscopic examination (n = 31) reveals the secretory ability of chief cells containing lots of secretory granules, and the energetic power of oxyphil cells filled with mitochondria. The great amount of oxyphil and of vacuolized cells after long periods of dialysis means degenerative transformation of ancient chiefs cells. The authors emphasize the interest of per-operative identification of the type of hyperplasia in order to choose the fitting procedure of parathyroidectomy.

[Association of a secreting oncocytic tumor of the kidney and a parathyroid adenoma]. / Association d'une tumeur oncocytaire sécrétante du rein et d'un adénome parathyroïdien.

An unusual association of a secreting renal oncocytoma and a parathyroid adenoma is described. The high level of hypercalcemia and of blood parathormone (PTH 44-68), partially reduced by nephrectomy and totally normalized by parathyroidectomy, as well as the renal tumor PTH evaluation and the ultrastructural features showing secretory granules in oncocytic cells of kidney, advocate for a double site of PTH secretion. Removal of both tumors permits a complete recovering.

[Carcinoma of the pancreas with amyloid stroma and calcitonin secretion : ultrastructural study (author's transl)]. / Carcinome pancréatique à stroma amyloïde avec sécrétion de calcitonine. Etude ultrastructurale.

The authors report a case of anaplastic carcinoma with amyloid stroma, accompanied by the secretion of calcitonin, detected in a cervical lymph node and initially interpreted as being a metastasis from a medullary carcinoma of the thyroid. The actual pancreatic origin of the malignant tumour was proved only during the advanced stages. Ultrastructural study confirmed the endocrine nature of the tumour (neurosecretory granules). Despite its exceptional character, the existence of such a tumour is not surprising, if one accepts the concept of a diffuse endocrine system.

[Vestigial retrorectal cyst in adults]. / Kyste vestigial rétrorectal de l'adulte.

STUDY AIM: The aim of this retrospective study was to report three cases of retrorectal vestigial cyst in adults. PATIENTS AND METHOD: From 1977 to 1999 retrorectal vestigial cyst (RVC) was diagnosed in our department in three women who were 28, 57 and 53 years of age, respectively. RVC was revealed by either pain (n = 2) that occurred in one case in a pregnant woman, or acute intestinal obstruction (n = 1). The patients were operated on using a perineal approach in two cases and an abdominal approach in one case. RESULTS: One epidermoid cyst and two mixed cysts without any sign of malignancy were observed. Postoperative follow-up was simple in two patients, while complications occurred in the third one via an uretero-vaginal fistula which required uretero-vesical reimplantation. The first two patients, reviewed after a 1-year follow-up, had no functional trouble and no sign of recurrence. CONCLUSION: Retrorectal vestigial cysts are very rare tumors with a risk for degeneration. Computerized tomography on nuclear magnetic resonance and endorectal ultrasonography allow detection of their structure and topography and help guide their surgical approach. In the absence of malignancy, wide excision, if possible without opening of the cystic wall, leads to good results.

[Subacute ischemia of the lower leg caused by a popliteal synovial cyst. Apropos of a case]. / Ischémie subaiguë du membre inférieur par kyste synovial poplité. A propos d'une observation.

Based on the observation of a cyst compressing the popiteal artery, the authors discuss the characteristic clinical picture and radiology of this benign neoformation. They emphasize two possible causes: cystic degeneration of the arterial median or a cyst of articular derivation. Histological data from this observation supports the second hypothesis.

[Pancreatic insulinoma. Peroperative topographical diagnosis]. / Insulinomes pancréatiques. Diagnostic topographique peropératoire.

Difficult problems may arise and place the surgeon in an uncomfortable position in cases where neither pre-operative investigations nor palpation of the pancreas have enabled pancreatic insulinomas to be localized. However, 3 examinations performed during the operation should help solve these problems, as shown by the case presented here. These examinations are insulin assays in the peripancreatic venous blood, blood glucose measurements under constant rate glucose infusion, and intra-operative ultrasonography. Pre-operative radioimmunological assays of insulin have been used for about 10 years, but owing to technical advances and shortening of the incubation time these assays can now be performed during surgery and, above all, with immediate results. Blood glucose measurements are good pointers, and this method has long been used in this type of surgery. Intra-operative ultrasonography has recently been introduced; it is very effective in diagnosing endocrine tumours of the pancreas, since the images it provides are quite characteristic. These 3 examinations combined should be used to localize pancreatic insulinomas; they may replace most of the pre-operative examinations that are still carried out.

[Contribution of immunologic technics to the characterization of lethal midline granuloma of unknown origin]. / Apport des techniques immunologiques au démembrement des granulomes malins centro-faciaux de cause inconnue.

The lethal midline granuloma is a clinical entity characterized by a relentless ulceration of the upper airway involving the nose, the palate and the face, without any demonstrable etiology. We have applied the cell membrane immunostaining techniques to twelve cases. According to the results, it seems that most of the cases are in fact T-cell lymphomas with membrane staining consistent with either precursor or mature lymphoid T-cells. Some cases, however, exhibit an immunostaining pattern compatible with other origins, the proliferating cells belonging either to the B lymphoid or to the histio-monocytic lineages. We conclude that the lethal midline granuloma is an heterogeneous group of neoplastic diseases, in the most part close to a T cell lymphoma, but with a remarkable clinical unity.

[Gastric duplications. A case report (author's transl)]. / Les duplications gastriques. A propos d'une observation personnelle.

The authors report an analysis of 154 true gastric duplications published up to now, and a personal case. This malformation occurs exceptionally and is generally discovered during the first year of life. Diagnosis is rarely performed before laparotomy, clinic signs being various. They insist on investigation by barium enema and fibroscopy. They try to oppose tubular to cystic forms, according to a different embryogenesis. Surgical treatment is specific to each case.

[Cystic dystrophy in an aberrant pancreas. Contribution of computerized tomography and MRI]. / Dystrophie kystique sur pancréas aberrant. Apport de la TDM et de l'IRM.

Case report of a cystic dystrophia appearing in an ectopic pancreas. The clinical diagnosis was preoperatively suspected by the findings of CT scan revealing a tumor located in the wall of the duodenum and by the data of MRI indicating its cystic and fibrotic structure. A focus of reacting pancreatitis was found in the vicinity of the cystic dystrophia while the remaining pancreas was normal. The surgical treatment was a duodenopancreatectomy, justified by the potential risks of complications.