Vascular pseudoinvasion in laparoscopic hysterectomy specimens for endometrial carcinoma: a grossing artifact?

Over several years, it has been a matter of debate whether or not the use of a uterine balloon manipulator during laparoscopic hysterectomies for endometrial carcinoma (EC) may cause tumor disruption resulting in a positive peritoneal cytology. More recently, this procedure has been associated with vascular pseudoinvasion in cases of low-risk EC. In this study, we evaluated a series of 21 cases of low-risk EC treated by laparoscopic hysterectomy (LH) to determine the incidence of this finding and to better characterize its histopathologic features. In addition, we reviewed 28 cases of low-risk EC treated by total abdominal hysterectomy (TAH) for comparison. Clinical information was obtained from patients' charts. Hematoxylin and eosin-stained slides were retrospectively reviewed in all cases. The following information was recorded: tumor grade and tumor stage according to the International Federation of Gynecology and Obstetrics, tumor shape (polypoid versus flat), presence or absence of vascular space involvement (VSI), size and location of the vessels with tumor involvement, concomitant presence of artifactual clefts in the myometrium with tumor involvement if applicable, presence or absence of lymph node sampling and the presence or absence of involvement at this site, and results of peritoneal cytology. Seven of 21 (33%) cases of low-risk EC treated by LH in this study showed VSI. None of the cases treated by TAH had VSI (P=0.001). In all of the cases of LH with VSI, the endometrial tumor was polypoid. VSI was detected only in large, thick-walled vessels in the outer myometrium or in ectatic vessels anywhere in the myometrium; no tumor fragments were seen in small vessels. The tumor in the VSI consisted of conspicuous fragments of tumors detached from the vascular wall. The VSI also lacked the inflammatory perivascular infiltrate seen in many cases of bona fide lymphovascular invasion. In addition, all of the cases with VSI also showed fragments of tumor in artifactual clefts in the myometrium. None of the cases of LH in which lymph node sampling and/or peritoneal cytology were obtained showed tumor at this site. In summary, our study confirms that LH is indeed associated with a higher rate of vascular pseudoinvasion when compared with TAH. However, we cannot attribute this phenomenon to mechanical disruption, displacement, and transport of tumor tissue into vascular spaces by the use of a uterine manipulator alone. Instead, we propose that pathologists may be generating postoperative pseudoinvasion by mechanically transporting tumor into vascular spaces during the grossing process. Proper recognition of this artifact is of utmost importance to avoid the overtreatment of patients undergoing LH for low-risk EC.     

Histologic variants of renal cell carcinoma: does tumor type influence outcome?

Each histologic type of renal cell carcinoma (RCC) has different pathologic and clinical parameters; however, the independent role of histologic type in outcome prediction remains contested. Most studies show relevance for outcome of each histologic type when correlated with survival by univariate analysis, whereas few studies show differences in outcome once other key prognostic factors, such as stage and grade, are considered. These studies highlight the challenges to prove outcome relevance. Despite the contested independent value of type for outcome prediction, separation of RCC into types is well accepted and can be substantiated on clinical, pathologic, molecular, and general outcome differences.     

Mifepristone as luteal phase endometrial contraceptive

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Hürthle cell carcinoma and "insular" carcinoma: uncommon varieties of thyroid carcinoma

The Hürthle cell carcinoma and "insular" carcinoma are two uncommon types of thyroid carcinoma. These neoplasms do not present accurate characteristics as to incidence, natural history, pathophysiology and therapies. Two cases are presented: the first was submitted to near-total thyroidectomy for Hürthle cell carcinoma, the second to total thyroidectomy for "insular" carcinoma with bone and lung metastases. Some literature previous studies on pathophysiology and natural history of both tumors are discussed. At the end, personal trend on the surgical treatment of these two thyroid neoplasms is presented: total thyroidectomy for CCh and "insular" carcinoma, and near-total thyroidectomy for Hürthle cell adenoma.     

Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity?

Although small cell carcinoma of the gastrointestinal (GI) tract is well-recognized, nonsmall cell type high-grade neuroendocrine carcinoma (HGNEC) of this site remains undefined. At the current time, neither the World Health Organization nor American Joint Committee on Cancer includes this condition in the histologic classifications, and consequently it is being diagnosed and treated inconsistently. In this study, we aimed at delineating the histologic and immunophenotypical spectrum of HGNECs of the GI tract with emphasis on histologic subtypes. Guided primarily by the World Health Organization/International Association for the Study of Lung Cancer criteria for pulmonary neuroendocrine tumors, we were able to classify 87 high-grade GI tract tumors that initially carried a diagnosis of either poorly differentiated carcinoma with or without any neuroendocrine characteristics, small cell carcinoma, or combined adenocarcinoma-neuroendocrine carcinoma into the following 4 categories. The first was small cell carcinoma (n=23), which had features typical of pulmonary small cell carcinoma, although the cells tended to have a more round nuclear contour. The second was large cell neuroendocrine carcinoma (n=31), which had a morphology similar to its pulmonary counterpart and showed positive immunoreactivity for either chromogranin (71%) or synaptophysin (94%) or both. The third was mixed neuroendocrine carcinoma (n=11), which had intermediate histologic features (eg, cells with an increased nuclear/cytoplasmic ratio but with apparent nucleoli), and positive immunoreactivity for at least 1 neuroendocrine marker. The fourth was poorly differentiated adenocarcinoma (n=17). In addition, 5 of the 87 tumors showed either nonsmall cell type neuroendocrine morphology (n=3) or immunohistochemical reactivity for neuroendocrine markers (n=2), but not both. Further analysis showed that most HGNECs arising in the squamous lined parts (esophagus and anal canal) were small cell type (78%), whereas most involving the glandular mucosa were large cell (53%) or mixed (82%) type; associated adenocarcinomas were more frequent in large cell (61%) or mixed (36%) type than in small cell type (26%); and focal intracytoplasmic mucin was seen only in large cell or mixed type. As a group, the 2-year disease-specific survival for patients with HGNEC was 25.4% (median follow-up time, 11.3 mo). No significant survival difference was observed among the different histologic subtypes. In conclusion, our study demonstrates the existence of both small cell and nonsmall cell types of HGNEC in the GI tract, and provides a detailed illustration of their morphologic spectrum. There are differences in certain pathologic features between small cell and nonsmall cell types, whereas the differences between the subtypes of nonsmall cell category (large cell versus mixed) are less distinct. Given the current uncertainty as to whether large cell neuroendocrine carcinoma is as chemosensitive as small cell carcinoma even in the lung, our data provide further evidence in favor of a dichotomous classification scheme (small cell vs. nonsmall cell) for HGNEC of the GI tract. Separation of nonsmall cell type into large cell and mixed subtypes may not be necessary. These tumors are clinically aggressive. Prospective studies using defined diagnostic criteria are needed to determine their biologic characteristics and optimal management.     

When is medullary thyroid carcinoma “medullary thyroid carcinoma”?

Medullary thyroid carcinoma (MTC) is thought to develop from the parafollicular or C cells within the thyroid gland and, therefore, should not take up radioactive iodine. Recently, however,¹³¹I uptake has been reported in metastases of medullary carcinoma and, consequently, some authors have suggested that these tumors can be treated with radioactive iodine. On the basis of observations in 5 patients out of 11 with MTC, we would like to comment regarding this situation. In our 5 patients who were treated by total thyroidectomy, the diagnosis of medullary carcinoma was made by experienced pathologists using immunohistochemical staining methods (calcitonin and/or thyroglobulin), peroxidase-antiperoxidase techniques, and electron microscopy. Evaluation of serum concentrations of calcitonin and serum thyroglobulin by radioimmunoassay was also performed. Data from our 5 patients provide evidence that patients with histopathological and immunohistochemical criteria for medullary thyroid carcinoma, and with high serum calcitonin levels, can take up¹³¹I. It is possible that these tumors represent poorly differentiated thyroid carcinomas with C-cell metaplasia or mixed tumors originating from both follicular and parafollicular cells. Other neoplasms classified as medullary cancer seem to be unspecified thyroid cancers with C-cell hyperplasia in the periphery of the tumor.

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Resumen Se considera que el carcinoma medular de tiroides (CMT) se desarrolla a partir de las células parafoliculares o células C de la glándula tiroidea y, por lo tanto, no debe captar yodo radioactivo. Sinembargo, recientemente se ha informado captación de¹³¹ I por parte de metástasis de carcinoma medular y como consecuencia algunos autores han sugerido que estos tumores pueden ser tratados con yodo radioactivo. Fundamentados en la observación de 5 pacientes entre 11 con CMT, procedemos a comentar esta situación. En 5 pacientes tratados con tiroidectomía total, el diagnosis de carcinoma medular fue hecho por patólogos expertos mediante métodos de coloraciön inmunohistoquímica (calcitonina y/o tiroglobulina), técnicas de peroxidasa-antiperoxidasa y microscopía electrónica. También se realizó la evaluación de las concentraciones séricas de calcitonina y de tiroglobulina sérica por RIA. Los datos obtenidos en nuestros 5 pacientes proveen evidencia de que pacientes con criterios histopatológicos e inmunohistoquímicos para sustentar el diagnosis de carcinoma medular de tiroides y con niveles elevados de calcitonina sérica pueden captar¹³¹I. Es posible que estos tumores representen carcinomas tiroideos pobremente diferenciados con metaplasia de células C o tumores mixtos de origen tanto en células foliculares como parafoliculares. Otros neoplasmas clasificados como carcinoma medular parecen ser cánceres tiroideos no especificados con hiperplasia de células C en la periferia del tumor.

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Résumé Le carcinome médullaire thyroïdien (MTC) est considéré comme se développant à partir des parafollicules ou des cellules C depuis l'intérieur de la glande thyroïde et ne capterait pas, par conséquent, l'iode radioactif. Par contre, récemment, la captation de¹³¹I a été décrite dans les métastases des carcinomes médullaires. Quelques auteurs ont suggéré que ces tumeurs seraient curables par l'iode radioactif. A partir de l'observation de 5 patients parmi 11 ayant un MTC, les auteurs souhaiteraient commenter les constatations précédentes. Ces 5 patients ayant subit une thyroïdectomie totale, le diagnostic de carcinome médullaire a été établi par des anatomopathologistes expérimentés, utilisant des méthodes de colorations immunohistochimiques (calcitonine et/ou thyroglobuline), des techniques de peroxydase-antiperoxydase et de microscopic électronique. Les concentrations sériques de calcitonine et de thyroglobuline sont dosées par RIA. Les données obtenues montrent à l'évidence que les patients ayant des critères histopathologiques et immunohistologiques de carcinome médullaire thyroïdien avec un taux sérique élevé de calcitonine peuvent capter¹³¹I. Il est possible que ces tumeurs représentent des carcinomes thyroïdiens peus différentiés avec métaplasie des cellules C ou des tumeurs mixtes ayant pour origine à la fois les cellules folliculaires et parafolliculaires. Les autres néoplasmes classés comme cancers médullaires semblent être des cancers thyroïdiens non spécifiques avec hyperplasie des cellules C en périphérie de la tumeur.

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Presented at the International Association of Endocrine Surgeons in Paris, September 1985.     

Determination of pyruvate kinase type tumor M2 in human renal cell carcinoma: a suitable tumor marker?

Renal cell carcinoma (RCC) expresses an isoform of the glycolytic enzyme pyruvate kinase (type M2). The dimeric form (TuM2-PK) is over expressed in tumor cells and is detectable in blood with a sensitive enzyme-linked immunosorbent assay (ELISA). The aim of the present study was to evaluate the clinical value of TuM2-PK as a tumor marker for RCC. The TuM2-PK concentration in EDTA-plasma was determined quantitatively and immunologically using an ELISA. We measured the TuM2-PK plasma levels of 83 patients before and after surgery. Ninety-seven patients with various non-malignant diseases were also recruited as a control group. The control group displayed mean levels of 11.37 U/ml of TuM2-PK. Values were elevated in patients with RCC prior to surgery (mean 21.88 U/ml). The plasma levels increased after surgery until day 5 (mean 53.97 U/ml). At day 10, marker levels started to decrease without reaching preoperative values (mean 43.5 U/ml). Plasma levels in the renal vein (obtained during surgery) were not different from those in the peripheral blood. Follow-ups after 2-6 months showed a decrease to below preoperative levels (mean 16.3 U/ml). A significant difference was obtained by comparing the patients according to their Robson score. We found a significant difference (P < 0.01, Wilcoxon's two-sample test) in TuM2-PK levels between patients with RCC and the control group. Nevertheless, using the manufacturer's recommended cut-off value (15 U/ml), sensitivity was only 50.6% and specificity was 80.4%. Our results suggest that TuM2-PK is not a suitable tumor marker for RCC.     

Does type II nitric oxide synthase expression correlate with cellular proliferation in oral squamous cell carcinoma and dysplasia?

BACKGROUND: Nitric oxide (NO) has been implicated both in tumor progression and inhibition. This study investigated whether type II nitric oxide synthase (NOS2) expression correlated with cell proliferation in oral squamous cell carcinoma (OSCC) and dysplasia. METHODS: Paraffin-embedded tissue samples of normal oral mucosa, OSCC, and dysplasia were assessed immunohistochemically using monoclonal antibodies to NOS2 and Ki-67 antigen. We used Western blotting to confirm NOS2 antibody specificity and protein expression in select cases. RESULTS: NOS2 staining was increased in OSCC relative to normal oral mucosa, in which no expression was found. Both NOS2 expression and Ki-67 indices independently correlated with grade of dysplasia (p < .001) but not with the degree of tumor differentiation. A positive correlation was found between NOS2 expression and Ki-67 in cases of mild and moderate dysplasia (p < .001), but not in severe dysplasia and OSCC. CONCLUSIONS: No correlation exists between Ki-67 and NOS2 expression in severe dysplasia and OSCC. The findings suggest that the level of NO produced by NOS2 is insufficient to affect cellular proliferation in these conditions. The mechanism of NOS2 activation and the consequences of its expression remain to be fully explained.     

Lymphadenectomy in gastric carcinoma?

Lymphadenectomy in gastric carcinoma is still discussed. Based on non-randomised and randomised studies D2-lymphadenectomy is indicated only in R0-resections. D2-lymph-node dissection requires great experience with this technique as well as for the management of possible postoperative complications. Survival advantages can be expected in patients with a limited nodal involvement, a favorable lymph node ratio between resected and involved nodes and in stage II disease. Therefore, survival improvement can be expected in 15-20 % of all R0-resections. Despite these limited prognostic advantages D2-lymphadenectomy should be performed in all R0-procedures since only the pathologic data of the resected specimen supply reliable prognostic parameter. If in the future sentinel lymphadenectomy allows selection criteria for a balanced indication for D2-lymphadenectomy in gastric carcinoma, needs to be awaited.     

Intravesical bacille Calmette-Guérin in the treatment of carcinoma in situ or high-grade superficial bladder carcinoma after radiotherapy for bladder carcinoma

OBJECTIVE: To evaluate the effectiveness and tolerance of endovesical bacille Calmette-Guérin (BCG) after pelvic radiation therapy for bladder cancer in patients with recurrence as carcinoma in situ (CIS) and/or high-grade superficial bladder cancer. PATIENTS AND METHODS: In a prospective study, 13 patients were treated with weekly instillations of 81 mg BCG Connaught for 6 weeks. for CIS and/or high-grade superficial bladder carcinoma. All had been treated previously with radical radiation therapy for bladder carcinoma. RESULTS: Five patients had no recurrences and six patients retained their bladders, within a median follow-up of 74.5 months. Five patients progressed; two underwent radical surgery and are alive after 75 months of follow-up, and three died from the disease (two were high-risk surgical patients and one had metastatic disease). Another two patients died from intercurrent disease without bladder cancer. Eight patients were alive at a mean (SD range) follow-up of 85 (12, 65-97) months. CONCLUSION: Intravesical BCG is useful for controlling CIS and/or high-grade superficial bladder carcinoma in irradiated bladders and has an acceptable local tolerance: more than a third of patients were free of disease and preserved their bladders. This proportion is acceptable in patients currently scheduled for cystectomy.     

Is it transitional cell carcinoma or renal cell carcinoma on computed tomography image?

We report on a 58-year-old female patient with renal cell carcinoma simulating transitional cell carcinoma on computed tomography. The computed tomography scan showed an enhancing 2.5-cm left renal pelvic mass without renal parenchymal mass. Urinalysis revealed microscopic hematuria. Cystoscopy and urine cytology was negative for transitional cell carcinoma. Laparoscopic nephroureterectomy was done under the preoperative diagnosis of localized transitional cell carcinoma of the renal pelvis according to the computed tomography findings. The histologic result, however, was a clear cell renal cell carcinoma.     

Anal metastasis of colonic carcinoma?

Two cases of sigmoid and anal adenocarcinoma are reported. The two patients were treated by abdominoperineal resection of the rectum and resection of the sigmoid colon. The relationship between colonic adenocarcinoma and anal adenocarcinoma is not obvious but possible. The various mechanisms of tumoral spread are discussed and the most frequent mechanism seems to be cellular exfoliation.     

Acute endometrial bowel obstruction—A rare indication for colonic stenting

INTRODUCTIONPelvic endometriosis is an extremely rare cause of large bowel obstruction and the management can be challenging. Urgent surgery for acute colonic obstruction is known to carry high morbidity and mortality, and operation may be made more difficult in extensive pelvic endometriosis. Less invasive alternatives in the acute situation may need to be considered.PRESENTATION OF CASEPresented is the case of a 35-year-old lady with obstructive bowel symptoms caused by an endometriotic upper rectal stricture. She was initially treated using radiologically guided stent insertion, as an acute intervention, prior to an elective bowel resection and hysterectomy with bilateral salpingo-oophorectomy.DISCUSSIONColonic stenting is currently widely used in malignant obstruction. The use of self expanding metallic stents (SEMS) to treat benign conditions is controversial, however, due to associated long term complications. This case demonstrates that stenting can provide a bridge to major surgery in the rare event of acute endometriotic colonic obstruction. The initial acute treatment with stenting provides the advantage of time to involve the multi-disciplinary team, to medically optimise the patient and to better plan the definitive surgery.CONCLUSIONThe use of radiologically guided stents has a place in the treatment of benign recto-sigmoid obstruction due to endometriosis and therefore should be considered as a bridge to further surgical treatment.     

Thyroid carcinoma associated with squamous cell carcinoma of the head and neck: Which policy?

BACKGROUND: Thyroid carcinoma occurring as a second primary associated with head and neck squamous cell carcinoma (HNSCC) is unusual. The clinical management of thyroid cancer in such cases has been debated. METHODS: Between 1975 and 2004, we collected 33 cases. The associated thyroid carcinoma was diagnosed either during or as a consequence of surgery planned as head and neck cancer treatment. RESULTS: The associated thyroid carcinoma was never seen to recur. Five-year overall survival was 41%. Disease-free survival after 40 and 66 months was 11.1% and 5.6%, respectively. CONCLUSIONS: We consider the treatment of thyroid cancer to be complete when the thyroid gland, either with or without lymph nodes, has been included in the specimen obtained during surgery for HNSCC. In the group of cases in which associated thyroid carcinoma was only found within the neck lymph nodes and the thyroid gland has not been treated, we discourage further surgical treatment or radioactive iodine therapy.     

Diagnosing endometrial hyperplasia: why is it so difficult to agree?

Current World Health Organization classification of endometrial hyperplasia is problematic because of poor diagnostic reproducibility. We sought to determine factors that cause diagnostic disagreement in a review of 2601 endometrial specimens. Blinded random specimens of normal endometrium, hyperplasias, and carcinoma were reviewed by 2 pathologists, with review by a third pathologist in cases with disagreement. All cases of endometrial hyperplasia or carcinoma were scored for degree of glandular crowding, architectural complexity, and cytologic atypia. Sample adequacy, hyperplasia volume, presence of metaplasia, or endometrial polyp were also scored. The overall kappa for agreement was 0.71, with a lower kappa of 0.36 when cases called "no hyperplasia" were excluded. The percent specific agreement was 90.3% for no hyperplasia, 31.1% for simple hyperplasia, 51.1% for complex hyperplasia, 49.8% for atypical hyperplasia, and 57.5% for adenocarcinoma. Cases categorized as "low volume hyperplasia" had more diagnostic disagreement than "high volume," (62% vs. 39%, P=0.003). Similarly, cases called "scant" had more diagnostic disagreement than "not scant" (65% vs. 57%, P=0.013). The histologic feature associated with the most diagnostic disagreement was cytologic atypia (P<0.0001). Architectural crowding, architectural complexity, or the presence of a polyp were all associated with diagnostic disagreement (P<0.0001). High diagnostic disagreement in endometrial hyperplasia is related to both sample adequacy and interpretation of histologic features present. Although obtaining additional tissue may increase diagnostic reproducibility, differences in interpretation of key histologic features like cytologic atypia remain major factors contributing to diagnostic disagreement.