Result of the implementation of multidisciplinary teams in rectal cancer.

AIM: In 2003 colorectal multidisciplinary teams (MDTs) were established in all major Danish hospitals treating colorectal cancer. The aim was to improve the prognosis by multidisciplinary evaluation and decision about surgical and oncological treatment, based on medical history, clinical examination, imaging, histology and comorbidity. The present study evaluates the effect of the introduction of colorectal MDTs on 1 August 2004 in two Danish hospitals. METHOD: A retrospective cohort study was conducted comparing the outcome during the last 3 years before introduction of MDTs with the first 2 years after (the MDT cohort). The national colorectal cancer database, with follow-up recorded by the National Patient Registry in September 2010 was used. The end-points included the incidence of preoperative radiochemotherapy offered according to the national guidelines, R0/R1/R2 resection, postoperative mortality, local recurrence, distant recurrence and over-all and disease-free survival. RESULTS: Eight hundred and eleven patients were diagnosed with primary rectal cancer in Hvidovre and Bispebjerg hospitals between 1 May 2001 and 31 August 2006. The frequency of preoperative MRI scans increased in the MDT cohort and perioperative mortality decreased. More metachronous distant metastases were found in the MDT cohort but there was no difference in overall survival. CONCLUSION: There was an improved postoperative mortality but no other potential benefits for the patients were seen after the implementation of colorectal MDTs.

Sessile serrated polyps of the colorectum are rare in patients with Lynch syndrome and in familial colorectal cancer families.

Whereas the generally accepted carcinogenesis pathway of the microsatellite instabile high (MSI-H) colorectal carcinoma (CRC) involves the traditional adenoma in patients with Lynch syndrome, a serrate pathway involving serrate adenomas (SA) and sessile serrate polyps (SSP) characterize the sporadic MSI-H counterpart. Recent studies have, however, challenged such simple one-pathway models, inviting the consideration of alternative, unexpected pathways. Here, the issue as to the possible role of SSP, primarily in the context of Lynch syndrome, but also in subjects from familial CRC families (FCF) is addressed. Polyps coded as hyperplastic polyps (HP) from subjects with Lynch syndrome and FCF enrolled in the HNPCC-register at the Hvidovre University Hospital as well as adenomas from this population were retrieved and reviewed for features of SSP. Ninety-eight polyps coded as HP and 41 polyps coded as adenoma from 14 individuals with Lynch syndrome as well as 17 individuals from FCF constituted the study material. Seven of the 98 polyps coded as HP displayed histological features that, to varying extent, deviated from the traditional HP (THP), yet, merely two of these, both from the FCF, were considered examples of probable SSP. None of the 41 cases coded as adenoma possessed a morphology that qualified as SSP. The prevalence of SSP was not increased as compared to the background population and thus, this serrated lesion does not appear to play a tumorigenic role in Lynch syndrome, nor in FCF.

Colorectal carcinoma with dome-like phenotype: an under-recognised subset of colorectal carcinoma?

BACKGROUND: The term dome carcinoma has been applied to a variant of colorectal carcinoma, thought to derive from M-cells of the gut-associated lymphoid tissue. Its distinguishing morphological features include a non-polypoid plaque-like lesion composed of closely apposed cystically dilated glands lined by a single layer of non-mucinous cells, intensely PAS-positive intraluminal material, and a close spatial relation to lymphoid stroma. AIMS AND METHODS: A search in the literature for such cases and the authors' experience with carcinomas sharing morphological details with dome carcinoma are presented to direct focus on this unique phenotype of colorectal carcinoma and to expand on its morphology. RESULTS: Four such examples, all stage pT1, pN0 have been previously reported. Here two additional cases, with several features of dome carcinoma, stage pT1 and pT2, respectively, are added. An extensive intramucosal component, unassociated with adenomatous growth, a pink quality of the lesional cells, low grade budding, absence of cytoplasmic pseudofragments, and absence of necrosis characterised the present cases as well as intact MMR-proteins and loss of APC. As opposed to two of the previously reported cases, intraepithelial lymphocytes were unapparent in these cases and the lymphoid stroma was effaced along with tumour progression in one of the present cases. Hence, a range of appearances is encompassed by the dome carcinoma. The uncommon reporting of dome carcinoma may be due to lack of awareness of this particular subset of colorectal carcinoma. Indeed, one of the current cases was signed out as a conventional carcinoma, despite the comment in the pathology report of an unusual morphology. CONCLUSION: Dome carcinoma may be more under-recognised than rare. The reporting of variants of colorectal carcinoma, displaying histological features suggestive of dome carcinoma, is encouraged in order to obtain more exact knowledge on its putative clinical significance.

Syncytin is involved in breast cancer-endothelial cell fusions.

Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to express ASCT-2, a receptor for syncytin. Syncytin antisense treatment decreases syncytin expression and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions.

False-negative frozen section of sentinel lymph node biopsy for breast cancer.

A prospective study is presented of frozen section examinations (FS) performed in parallel with 265 consecutive sentinel lymph node procedures (SLNP) over a 20-month period. The final pathological study included immunohistochemistry (IHC) for keratin if the haematoxylin-eosin (HE)-stained section was tumour free. FS correctly identified node-positive or node-negative axillae in 235 cases. In 28 SLNPs the final examination gave a positive result not detected in the FS, resulting in reoperation. In 21 of these false-negative (FN) cases micrometastases (MIM) were present. There were no false-positive cases, but in two cases of lobular carcinoma the findings in the FS were equivocal, the final reports recording metastases in one but not in the other. Lobular carcinoma and other less common subtypes of carcinoma were overrepresented, ductal carcinoma not otherwise specified (NOS) being less likely to affect the FN findings.

Ossifying fibromyxoid tumour of soft parts, with focus on unusual clinicopathological features.

AIMS: Ossifying fibromyxoid tumour is a rare lesion that generally occurs in the soft tissues of proximal limbs/girdle, or head and neck. Histologically, it usually consists of bland, mitotically inactive, S100+ cells in a fibromyxoid matrix with a characteristic peripheral ossification. However, we present two cases that deviated from this pattern. MATERIAL AND METHODS: One tumour, which was removed from the axilla of a 55-year-old female, was unusual in its large size (120 mm in diameter) and in its restriction of bone formation to its central zones. The other tumour, which occurred in a 62-year-old female, was remarkable in its acral location on the hand and high mitotic activity (four mitoses per high-power field). These features caused concern and follow-up of the patients was recommended. So far there have been no recurrences (25 and 18 months after surgery, respectively). An additional previously undescribed feature was the presence of fibronexus-like structures by electron microscopy in the second case. However, a myofibroblastic phenotype was not supported by the immunohistochemical findings. CONCLUSION: Though a distinct entity, ossifying fibromyxoid tumour may exhibit a wider clinicopathological spectrum than generally recognized.

Gastric mucosal cytokine responses in Helicobacter pylori-infected patients with gastritis and peptic ulcers. Association with inflammatory parameters and bacteria load.

Helicobacter pylori is an important pathogen in gastroduodenal inflammation and ulceration. Several mechanisms have been proposed to explain its role. We studied the cytokine production patterns in situ in gastric mucosal biopsies from H. pylori-positive and H. pylori-negative patients with dyspepsia. Immunohistochemistry with monoclonal antibodies was used. The study showed enhanced expression of interleukin (IL) -8, IL-10 and interferon-gamma (IFN-gamma) in H. pylori infection and a significant association was found between these cytokines and the following parameters: bacteria load, chronic inflammation and activity. These parameters were significantly correlated with the cell markers CD19 and CD56. The study indicates a dual effect of H. pylori on the Th1 response, i.e. a stimulation of the response verified by increased IFN-gamma and a feed-back verified by an increase of the counterinflammatory IL-10, which may dampen the inflammatory and cytotoxic effect of the Th1 response. Furthermore, the study confirms the connection between increase of IL-8 and inflammatory activity in gastric mucosa in H. pylori infection.

Different patterns of Helicobacter pylori adherence to gastric mucosa cells in children and adults. An ultrastructural study.

BACKGROUND: Infection with Helicobacter pylori in childhood may be the initiation of a lifelong coexistence between microorganisms and epithelial cells resulting in chronic inflammation. The adhesion pattern of H. pylori found in antral biopsies from a group of H. pylori-infected children with recurrent abdominal pain was compared with a group of H. pylori-infected adults suffering from dyspepsia, in an attempt to reveal differences in the type of adhesion. METHODS: The histology of antrum biopsies and the ultrastructure of adherent H. pylori in biopsies from 26 children (median age, 10.1 years) were compared with organisms in biopsies from 19 adults (median age, 54.4 years). RESULTS: More than 1000 adherent H. pylori were studied and divided into four types of adhesion: 1) contact to microvilli; 2) connection to the plasma membrane via filamentous material; 3) adhesive pedestal formation; and 4) abutting or making a depression in the plasma membrane. Contact to microvilli was significantly higher (69% versus 39%; P = 0.002) in children compared with adults and comprised two-thirds of all adherent organisms in children. The more intimate adhesion types as abutting or adhesive pedestals dominated in adults. CONCLUSIONS: These results indicate a change in contact types between H. pylori and gastric epithelial cells in adults compared with children and this may be a natural development in the lifelong infection of humans.

Extraorbital giant cell angiofibroma.

A number of intriguing fibrovascular mesenchymal proliferations with benign or low grade malignant potential have recently been described. Giant cell angiofibroma was introduced as an entity by Dei Tos et al. in 1995 and initially considered to be a lesion of the orbit. We describe an extraorbital example, indicating that giant cell angiofibroma is not confined to the orbit. Immunologically, giant cell angiofibroma is positive for CD 34, bcl-2 and vimentin, and negative for epithelial and muscle markers, and S-100. The tumor shares several morphological and immunological properties with giant cell fibroblastoma and solitary fibrous tumor, yet it features a histology sufficiently characteristic to allow its categorization as a separate entity. The recommended treatment is complete but conservative excision. Metastases have not been reported.

Endothelial cell nitric oxide synthase in peritumoral microvessels is a favorable prognostic indicator in premenopausal breast cancer patients.

Nitric oxide (NO) is involved in tumor cell apoptosis and has additional effects on tumor blood flow, immune responses, and angiogenesis. We, therefore, studied endothelial cell NO synthase (ecNOS) protein expression in a retrospective series of 118 patients with primary invasive breast cancer. Immunocytochemically stained paraffin sections were used for determining the frequency of (a) tumor cells, (b) intratumoral microvessels, and (c) peritumoral microvessels that were positive for ecNOS. A high density of ecNOS positive microvessels in the normal tissue surrounding the tumor (measured by the variable PEMVD) was associated with significantly better recurrence-free and overall survival. The prognostic significance was observed in a representative series of premenopausal patients and was independent of other factors, including lymph node status. The counting procedure was highly reproducible and correlated to stereological measurements but was influenced by heterogeneity of the tissue samples. Analyzing two sections per patient improved the discriminative power by reducing the influence of tissue heterogeneity and produced highly significant results (recurrence-free survival, P < 0.001; overall survival, P < 0.0001). Immunoreactive ecNOS in microvessels is an independent prognostic factor in breast cancer and may reflect a mechanism of endothelial defense against invasion by tumor cells. Individual variations in ecNOS may be related to environmental, hormonal, and genetic factors and could represent a therapeutic target.

Characterization of a culturable "Gastrospirillum hominis" (Helicobacter heilmannii) strain isolated from human gastric mucosa.

Spiral organisms were isolated from an antral gastric mucosal biopsy specimen from a dyspeptic patient with gastritis. Only corkscrew-shaped organisms resembling "Gastrospirillum hominis" ("Helicobacter heilmannii") but no Helicobacter pylori-like organisms were seen in histological sections. H. pylori was not cultured from specimens from this patient. On the basis of biochemical reactions, morphology, ultrastructure, and 16S DNA sequencing, the isolated "G. hominis" was shown to be a true Helicobacter sp. very similar to Helicobacter felis and the "Gastrospirillum" but was separate from H. pylori. "G. hominis" is a pleomorphic gram-negative cork-screw-shaped, motile rod with 3 to 8 coils and a wavelength of about 1 micrometer. In contrast to H. pylori, it has up to 14 sheathed flagellar uni- or bipolar fibrils but no periplasmic fibrils. "G. hominis" grows under microaerobic conditions at 36 and 41 degrees C on 7% lysed, defibrinated horse blood agar plates within 3 to 7 days and can be subcultured under microaerobic but not under anaerobic conditions on media similar to those used for H. pylori and H. felis. The small translucent colonies were, in contrast to those of H. felis, indistinguishable from those of H. pylori. "G. hominis" is, like H. pylori and H. felis, motile, is oxidase, catalase, nitrite, nitrate, and urease positive, and produces alkaline phosphatase and arginine arylamidase. Like H. pylori and H. felis, it is sensitive to cephalothin (30-microgram disc), resistant to nalidixic acid (30-microgram disc), and sensitive to most other antibiotics. The 16S DNA sequence clusters "G. hominis" together with "Gastrospirillum," H. felis, Helicobacter bizzozeronii, Helicobacter salmonii, Helicobacter nemestrinae, Helicobacter acinonychis, and H. pylori.

Quantification of microvessel density of breast carcinoma: an assessment of the inter- and intraobserver variation.

The density profile of microvessels (MVD) has recently emerged as a prognostically independent morphological marker of various malignancies, including carcinoma of the breast. MVD-scoring may thus afford the pathologist the opportunity to identify subsets of early stage breast cancer patients, which may benefit from adjuvant therapy. Reproducibility studies are, however, mandatory. Fifty sections of invasive breast carcinoma, immunolabelled for Factor VIII-related antigen, were scored independently by two observers for the number of vessel-profiles (v-p) in the following manner: 1) 250 randomly selected high power fields (HPF) were scored by two analysts to evaluate the agreement of the counting per se; and 2) the hot spot(s), i.e. the zones considered the most vessel rich, in the 50 sections were identified and scored twice to evaluate the agreement on selecting hot spots. When the observers evaluated MVD in the very same 250 HPF a median deviation of 2 v-p (10%) was produced. The interobserver disparity was further accentuated when the participants independently had to identify the hot spots with a median deviation of 6 v-p (13%). Intraobserver variation was approximately equal to the interobserver discordance. Divergences were most conspicuous in fields with a complex vasculature. In conclusion the v-p scoring resulted in substantial inter- and intraobserver variation both in selecting hot spots and in performing the scoring per se. Alternative-scoring techniques, including strict stereological principles, should be considered in the morphological evaluation of angiogenesis.

The histopathology of human gastric mucosa inhabited by Helicobacter heilmannii-like (Gastrospirillum hominis) organisms, including the first culturable case.

The aim was to determine the prevalence of Helicobacter heilmannii-like organisms in human gastric biopsies and the associated histology compared with that of Helicobacter pylori-bearing gastric biopsies. Furthermore, the feasibility of culturing H. heilmannii was examined. A consecutive series of 727 gastric biopsies from 650 patients were prospectively scrutinized for H. heilmannii. Their distribution pattern was recorded as well as the affiliated morphology of the gastric mucosa. Additional biopsies from some of the patients were examined microbiologically. Four cases (0.6%)(95% confidence intervals: 0.01-1.2%) of the examined material harboured H. heilmannii. The bacterial burden was graded as sparse in three cases, moderate in one case. The distribution pattern was patchy; thus, in no case did all biopsies from one endoscopy comprise H. heilmannii. Adhesion to epithelial cells was infrequent. A mild gastritis, active in three cases, characterized all biopsies. Lymphoid aggregates occurred in biopsies from three patients. Micropapillary tufting of the epithelial layer and intestinal metaplasia were not apparent. Culture studies proved successful in the one of the four cases assayed. In conclusion the morphology of H. heilmannii-bearing mucosa deviates from that of H. pylori-associated mucosa by the absence of epithelial damage in the former. This observation can in part be explained by the predominant location of H. heilmannii at a distance from the epithelium in contrast to the conspicuous H. pylori adhesion to epithelial cells, coupled with a usually low bacterial burden and patchy occurrence of H. heilmannii as opposed to the generally more heavy infestation with H. pylori.

Radiation-associated angiosarcoma of the small bowel. A case of multiploidy and a fulminant clinical course. Case report.

Angiosarcoma developing in unusual sites such as the gastrointestinal tract is not uncommonly associated with a known eliciting factor. Thus, among hitherto reported cases of angiosarcoma of the small bowel, five were radiation-associated. One additional example of ileal angiosarcoma induced by therapeutic irradiation of endometrial carcinoma is herein reported as a reminder of this causal association. DNA analyses of the primary growth as well as the metastatic deposits showed at least four aneuploid cell clones indicating genetic instability. This observation corresponds to the consistently poor prognosis of radiation-associated angiosarcoma of the small bowel.

Specific neutrophil hyporesponsiveness in chronic Helicobacter pylori infection.

The release from mucosal neutrophils of reactive oxygen species (ROS) is believed to be an important part of the pathogenesis of Helicobacter pylori-associated gastritis and duodenal ulcer. In this study, bacterial sonicates prepared from 1 reference and 29 patient strains were used to stimulate ROS release from peripheral blood neutrophils. In 29 H. pylori-positive patients, the neutrophil response toward the homologous strain was absent. In contrast, a significant response was observed toward the reference strain. In addition, on stimulation of neutrophils from 29 patients without H. pylori infection, ROS release was significant. The stimulatory effect on neutrophils by FMLP was comparable in the 2 groups. It is concluded that a specific neutrophil hyporesponsiveness in ROS release toward the homologous R. pylori strain exists. This feature has, to our knowledge, not been described previously for neutrophil responses to any human pathogen.

Solid glomus tumor presenting as an axillary mass: report of a case with morphologic study, including cytologic characteristics.

BACKGROUND: Glomus tumors are usually small, painful, subungual nodules causing no diagnostic difficulties. Less obvious is the characterization of the solid, deep-seated variant. CASE: A 32-year-old female presented with a solid, painless tumor in the right axillary region. A fine needle aspirate was initially interpreted as ectopic breast tissue. Subsequent morphologic studies on the lumpectomy specimen revealed a solid glomus tumor. CONCLUSION: The cytologic appearance of glomus tumors is at most suggestive. Whenever the diagnosis is considered, appropriate immunohistochemical studies should be added to consolidate it.