External multicentre validation of pseudomyxoma peritonei PSOGI-Ki67 classification.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignant disease. Adding of the Ki67 proliferation index to the PSOGI PMP classification provided two different subcategories of the extensive HG-PMP group (HG-PMP ≤15% and HG-PMP >15%) with different survival in a previous unicentric study. This study aims to carry out an external and multicentre validation of this new proposed classification. METHOD: It was a prospective analysis of samples from a historical and international cohort of patients. A representative area with higher cellular density was used to determine the Ki67%. The Ki67 proliferation index (%) was determined in all the HG-PMP patients. A Cox proportional hazard models and multivariable COX models were used. The Kaplan-Meier method and the two-tailed log-rank test were used to analyse the effect of different PSOGI-Ki67 categories on OS and DFS. Its predictive accuracy was analysed using Harrel's C-index and the ROC curve. The calibration was performed using the calibration plots matching. RESULTS: After exclusions, 349 patients were available for analysis. The 5-years OS were 86% for LG-PMP, 59% for HG-PMP≤15, 38% for HG-PMP>15 and 42% for SRC-PMP (p = 0.0001). The 5-years DFS were 49% for LG-PMP, 35% for HG-PMP≤15, 16% for HG-PMP>15 and 18% SRC-PMP (p = 0.0001). The discrimination capability of PSOGI-Ki67 was validated. CONCLUSION: the PSOGI-Ki67 classification discriminates and predicts the OS and DFS in patients with PMP dividing the HG-PMP category into two well-defined sub-categories. The Ki67 proliferation index should be incorporated routinely in the pathology report for these patients.

The appendix "mucocoele" misnomer: radiological terminology of "likely appendix mucinous neoplasm" better reflects pathology findings.

AIM: To review the radiological terminology used to describe dilated mucin-containing appendiceal lesions with correlation to the histopathological diagnosis. MATERIALS AND METHODS: Radiology and histopathology reports for all patients with an abnormally dilated appendix referred to a tertiary peritoneal malignancy centre, between January 2021 and December 2021, were reviewed. RESULTS: Overall, 213 patients were included with a median appendiceal diameter of 25.5 mm (range 10-125 mm). Peritoneal disease was present in 109 patients, with the remaining 104 cases demonstrating a dilated appendix only. Local radiology reports were available for 201 cases with the appendix described in 168 cases as appendiceal mucocoele (n=104), appendiceal neoplasm (n=40), appendicitis (n=18), and dilated appendix (n=6). The appendix was not mentioned in 33/201 (15%), either misinterpreted as other pathology (n=15) or not reported (n=18). Peritoneal malignancy histopathology reports were available in 188 cases and reported as low-grade appendix mucinous neoplasm (LAMN, n=144), high-grade appendix mucinous neoplasm (HAMN, n=13), LAMN with foci of HAMN (n=2), LAMN with neuroendocrine tumour (n=2), LAMN with goblet cell adenocarcinoma (n=1), goblet cell adenocarcinoma (n=8), mucinous adenocarcinoma (n=14), non-mucinous adenocarcinoma (n=1), and benign histology (n=3). Only one case of a true inflammatory "mucocoele"/retention cyst was reported. CONCLUSION: In this cohort of patients, the overwhelming majority of dilated, mucin-filled appendices contained malignant cells and benign mucin-filled appendices were rare. The present authors advocate that the term "likely appendix mucinous neoplasm" should replace "appendix mucocoele" to represent the most likely pathology and facilitate less ambiguous interpretation in management decisions.

Not all abdominal masses after colorectal cancer surgery are malignant: intra-abdominal fibromatosis masquerading as recurrence.

AIM: Intra-abdominal fibromatosis is an unusual mesenchymal tumour that can be locally aggressive without any metastatic potential. Fibromatosis may simulate cancer recurrence on imaging surveillance for colorectal cancer follow-up. The optimal treatment of recurrent peritoneal malignancy is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Confirmatory biopsy of lesions suspicious for colorectal cancer recurrence may not be feasible, thereby rendering surgery the safest option. Our aim was to determine the incidence of fibromatosis in a cohort of patients undergoing CRS and HIPEC for suspected colorectal cancer recurrence. METHODS: One hundred and seventy-one CRS and HIPEC cases were performed at our Peritoneal Malignancy Institute between February 2007 and October 2018 for colorectal peritoneal metastases and were included in a prospectively maintained database. RESULTS: A total of 49 (29%) of 171 cases were performed for primary colorectal cancer with peritoneal metastases, whereas 122 (71%) of 171 cases were performed for suspected colorectal cancer recurrence detected on surveillance imaging after primary colorectal cancer resection. On histological analysis of the resected specimen, five (4.1%) of 122 cases undergoing CRS and HIPEC for colorectal recurrence had fibromatosis. CONCLUSION: Fibromatosis can masquerade as colorectal cancer recurrence. In this series it occurred with an incidence of 4.1% among a cohort of patients undergoing CRS and HIPEC for probable recurrence. Surgical resection may be the only option to confirm the diagnosis and rule out malignancy.

Primary cutaneous nodular amyloidosis associated with psoriasis.

Primary cutaneous nodular amyloidosis (PCNA) presents as solitary or multiple firm, waxy nodules with a predilection for acral areas. Histologically, PCNA can be identical to myeloma-associated systemic amyloidosis with monoclonal immunoglobulin light chain deposits. We describe a patient in whom PCNA developed in a scar in an area affected by chronic plaque psoriasis. PCNA has previously been associated with other autoimmune diseases, but to our knowledge, this is the first association with psoriasis. Interestingly, T helper (Th)17 cells, which are crucial in psoriasis pathogenesis, have recently been implicated in promotion of myeloma and plasma cell dyscrasias. The association of psoriasis and plasma-cell light chain production in the skin, as in this case, suggests a possible role for Th17 cells in PCNA formation. The dermatopathological literature of this rare but important disease is discussed.

A combination of assays reveals biomass differences in biofilms formed by Escherichia coli mutants.

AIMS: The aim of this study was to develop an assay system that can quantify the amount of biomass in biofilms formed by different isogenic mutants of an Escherichia coli K-12 strain. METHODS AND RESULTS: The reported assay, which is based on the BacTiter-Glo assay from Promega, uses bioluminescence to detect the intracellular concentration of ATP, which correlates with viable bacterial cell numbers. The quantitative data obtained with this ATP assay were compared to those obtained with the conventional crystal violet assay. As a qualitative control, scanning electron microscopy was performed. CONCLUSIONS: The ATP assay, the crystal violet assay and scanning electron microscopy yielded similar results for six of the eight strains tested. For the remaining two strains, the images from the scanning electron microscopy confirmed the results from the ATP assay. SIGNIFICANCE AND IMPACT OF THE STUDY: The ATP assay, in combination with other quantitative and qualitative assays, will allow us to perform genetic studies on the regulatory network that underlies the early steps in E. coli biofilm formation.

Serrated and non-serrated polyps of the colorectum: their prevalence in an unselected case series and correlation of BRAF mutation analysis with the diagnosis of sessile serrated adenoma.

AIMS: To determine the prevalence of colorectal polyps of different types in an unselected population, and to correlate the morphological diagnoses with BRAF mutation analysis. METHODS: Cases of colorectal polyps diagnosed at endoscopy were retrieved from the files of Southern.IML Pathology. All slides were reviewed and the lesions classified histologically. A diagnosis of sessile serrated adenoma was made even if the characteristic features were present only focally. If there was more than one polyp of a particular type in any patient, one lesion was chosen at random so that the results represent the number of patients with each type of polyp rather than the total number of polyps. A proportion of the polyps was subjected to BRAF mutation analysis. RESULTS: A total of 1479 patients were identified. Non-serrated ("conventional") adenomas were found in 964 patients (65%), hyperplastic polyps in 437 (30%), sessile serrated adenomas in 57 (3.9%), traditional serrated adenomas in 11 (0.7%) and mixed hyperplastic adenomatous polyps in 10 (0.7%). BRAF V600E mutation analysis was performed in 148 selected cases; mutations were found in 44/49 (90%) of lesions diagnosed as sessile serrated adenoma, in 10/34 (29%) of hyperplastic polyps of microvesicular type, in 4/11 (36%) of traditional serrated adenomas, in 10/10 (100%) of mixed hyperplastic adenomatous polyps, and in 2/42 (5%) of "conventional" adenomas. CONCLUSIONS: Sessile serrated adenomas are encountered commonly in routine endoscopy practice. The histological diagnosis correlates strongly with the presence of BRAF mutation.

Hyperplastic polyps of the duodenum: an unusual histological finding.

A 58-year-old man underwent upper gastrointestinal surveillance endoscopy for Barrett's oesophagus. This showed a possible gastric ulcer, although histological examination was normal. Follow-up endoscopy showed white ridges in the distal duodenum and these were subjected to biopsy. Histological examination of the biopsy specimens showed polypoid duodenal mucosa showing features similar to those of a hyperplastic polyp of the colon. In addition, the mucosal surface was focally of gastric surface type. The features were interpreted overall as most likely to represent an unusual form of regenerative change in the setting of previous chronic inflammatory mucosal damage. The case is presented as an unusual histological phenomenon at this site; it would be important not to overdiagnose neoplasia in this situation.

Looking 'back to the future': alumni perceptions of a UK undergraduate medical programme.

The five year Bachelor of Medicine (BM5) programme of the University of Southampton commenced in 1971. In keeping with other medical schools, the Southampton BM5 programme has been involved in a number of incremental curriculum reforms over the years. Complementing the School's annual pre-registration house officer (PRHO) questionnaire, this study of alumni cohorts (2000-2003) sought to investigate further how past graduates view their medical education and whether there are emerging priorities in medical practice. Findings confirm that alumni rate the BM5 highly and generally value the BM5 aims. Considering the impact of the social context on individual well-being and patient care, increased emphasis may need to be placed on preventive medicine, including greater alignment of several curriculum areas with clinical practice.

The retroperitoneal surface in distal caecal and proximal ascending colon carcinoma: the Cinderella surgical margin?

BACKGROUND: Mesorectal margin tumour involvement is a predictor of local recurrence in rectal carcinoma and an indication for postoperative radiotherapy in suitable patients. However, the prevalence of non-peritonealised surgical margin involvement in ascending colon carcinoma is unknown. AIMS: To test the hypothesis that retroperitoneal surgical margin (RSM) tumour involvement occurs in distal caecal and proximal ascending colon carcinoma. METHODS/RESULTS: One hundred right hemicolectomy specimens, removed for adenocarcinoma of the caecum or proximal ascending colon, were studied. During routine specimen dissection, at least one additional tissue block was taken to include the tumour and the RSM. The tumour distance from the RSM was recorded. RSM tumour involvement was present in seven cases (7%). Direct (non-nodal) RSM tumour involvement (five cases) only occurred in posterior or circumferential tumours. CONCLUSIONS: RSM tumour involvement occurs within a considerable number of distal caecal and proximal ascending colon carcinomas. The rate of RSM tumour involvement identified here is similar to a previously published local recurrence rate of 10% in caecal carcinoma, suggesting that RSM tumour involvement may be a predictor of recurrence in these tumours. Therefore, patients with distal caecal or proximal ascending colon carcinoma and RSM tumour involvement may benefit from postoperative radiotherapy.

Histopathological assessment of lymph nodes in colorectal carcinoma: does triple levelling detect significantly more metastases?

AIMS: Standard practice is to take one section from every lymph node found in colorectal carcinoma resection specimens, to look for metastatic carcinoma. This study evaluates whether assessing three sections separated by 100 microm detects significantly more metastases in nodes than the conventional single section. METHODS: A retrospective study of 100 colorectal carcinoma resection specimens. All blocks containing lymph nodes had two extra histological sections cut (separated by 100 microm) and stained with haematoxylin and eosin. The original slide was called level 1, and the extra two sections levels 2 and 3. RESULTS: Twenty Dukes's A (equivalent to WHO-UICC stage grouping I, pTNM stage pT1/2N0), 43 Dukes's B (equivalent to WHO-UICC stage grouping II, pTNM stage pT3/4N0), and 37 Dukes's C (equivalent to WHO-UICC stage grouping III, pTNM stage at least pN1) cases were examined (total 1453 nodes). Twelve extra metastases (in 11 patients) were discovered in nodes at levels 2 and 3, which were negative in level 1. Ten cases were Dukes's C and, in one patient, this led to upstaging from N1 to N2 (pTNM classification system). One case was Dukes's B and the discovery of a single metastasis on level 2 upstaged it to Dukes's C. CONCLUSIONS: Triple levelling detected more tumour deposits than the conventional single section. In two patients, the staging classification of the lesion was changed, with potentially important implications for prognosis and management.

Deficient alpha smooth muscle actin expression as a cause of intestinal pseudo-obstruction: fact or fiction?

AIMS: To test the hypothesis that deficient alpha smooth muscle actin (ASMA) expression in intestinal smooth muscle, as assessed by immunohistochemistry, is specifically associated with clinical evidence of intestinal pseudo-obstruction. METHODS: Seventeen archival, formalin fixed, paraffin wax embedded samples of small intestine and 12 samples of large intestine were studied. Two of the small bowel samples and one large bowel sample were from patients with symptoms of intestinal pseudo-obstruction. The controls were longitudinal surgical margins from hemicolectomies performed for carcinoma. Immunohistochemistry was performed using primary antibodies to ASMA, smooth muscle myosin heavy chain (SMMHC), and desmin. The relative intensities of immunohistochemical expression in the circular and longitudinal muscle layers of the muscularis propria were assessed in each sample, for all three markers. RESULTS: All samples showed strong SMMHC and desmin expression in the inner circular and outer longitudinal layers of the muscularis propria. Both small intestinal samples from the cases and 11 of 15 controls showed no or minimal ASMA expression in the inner circular layer, with the remaining four controls also showing ASMA labelling in this layer that was weaker than within the longitudinal muscle. In contrast, intense ASMA expression was seen in both muscle layers within the large intestine in the remaining case, and in the controls. CONCLUSIONS: There is insufficient evidence from this study to support the hypothesis that ASMA deficiency in intestinal smooth muscle, as determined by immunohistochemistry on archival tissues, is specifically associated with intestinal pseudo-obstruction.

Expression of cytokeratins 7 and 20 in carcinomas of the gastrointestinal tract.

AIMS: The differential expression of cytokeratin (CK) 7 and 20 by carcinomas may help in determining the primary site of a metastatic tumour. The aim of this study was to extend the published data on CK7 and CK20 expression in epithelial neoplasms of the gastrointestinal tract by considering the degree of differentiation and including some unusual neoplasms. METHODS AND RESULTS: Cases referred to the Armed Forces Institute of Pathology were studied prospectively for immunohistochemical expression of CK7 and CK20. Lesions from 105 patients were analysed. Adenocarcinomas of the upper gastrointestinal tract were positive for both CK7 and CK20 in 78% of cases; only poorly differentiated lesions were CK7-. Well-differentiated and moderately differentiated adenocarcinomas of the large intestine, including appendix, were CK7-/CK20+ in the great majority of cases, as were goblet cell carcinoids, but half of the poorly differentiated adenocarcinomas exhibited aberrant expression, as did most of the mixed goblet cell carcinoid/adenocarcinomas. All five high-grade neuroendocrine carcinomas were negative for both CK7 and CK20. CONCLUSIONS: Not only the site but also the grade and histological type of a gastrointestinal carcinoma should be considered when assessing cytokeratin phenotype.

A mucinous tumour of the urachus: adenoma or low grade mucinous cystic tumour of uncertain malignant potential?

We report a case of urachal glandular neoplasia in a male aged 72 years. The lesion had a papillary and villiform structure, and exhibited serrated features as seen in some colorectal neoplasms. The tumour cells expressed carcinoembryonic antigen, whereas the normal urachal epithelium did not. There was a striking resemblance to low grade mucinous cystic tumours of uncertain malignant potential as described in the appendix and elsewhere. Although such lesions in the urachus have been called adenomas, we argue that their potential to cause pseudomyxoma peritonei deserves a different terminology, and that 'mucinous tumour of uncertain malignant potential' is appropriate.

Vascular resistance in human muscle flaps.

Important differences in free muscle flap survival have been reported in the setting of long arterial and venous vein grafts. The authors provide insight into the etiology of flap failure by addressing the following question: Do differences in flap type result in clinically significant different vascular resistances and consequently anastomotic patency? A total of 15 human flaps were studied intraoperatively: 9 gracilis, 3 rectus abdominis, and 3 latissimus dorsi. The muscle was isolated on a single pedicle and hemodynamic stability was ensured. The venous pedicle was then divided. A timed collection of effluent was used to determine flow. Vascular resistance was calculated by dividing the change in pressure by the flow, and standardizing this for temperature and hematocrit. Average vascular resistance and standard deviation for the gracilis, rectus, and latissimus flaps was 10.34 +/- 7.77 mmHg per milliliter per minute, 2.79 +/- 1.50 mmHg per milliliter per minute, and 3.17 +/- 1.05 mmHg per milliliter per minute respectively. An inverse relationship between muscle vascular resistance and flap mass was found (p < 0.001). This indicates that larger muscles have less vascular resistance. The decreased resistance gives rise to higher flow rates and, as a result, potentially improved vein graft patency. The clinical implication is that a larger flap should be used when high flow-through is critical. The role of flap vascular territory makeup continues to be pursued.

M30 expression demonstrates apoptotic cells, correlates with in situ end-labeling, and is associated with Ki-67 expression in large intestinal neoplasms.

CONTEXT: The monoclonal antibody M30 recognizes a neoepitope of cytokeratin 18 produced during apoptosis. It is reactive in formalin-fixed, paraffin-embedded tissue and has great potential in the study of apoptosis in clinical and experimental material. OBJECTIVES: To compare the results of M30 immunoexpression with a more established technique of demonstrating apoptosis in tissue sections, in situ end-labeling. A secondary objective was to compare the results with immunoexpression of the proliferation-associated antigen Ki-67. DESIGN: Retrospective analysis of adenomas and adenocarcinomas of the large intestine. INTERVENTIONS: Immunohistochemistry for M30 and Ki-67, and in situ end-labeling. Formalin-fixed, paraffin-embedded tissue was used. MAIN OUTCOME MEASURES: The number of cells positive for M30, Ki-67, and in situ end-labeling, expressed as a proportion of the total number of cells counted. RESULTS: A strong positive correlation was found between in situ end-labeling and expression of M30, although the counts were widely scattered around the regression line. Counts of Ki-67 were strongly correlated with both M30 expression and in situ end-labeling. Immunoexpression of M30 was generally easier to interpret than in situ end-labeling, and the procedures for M30 immunohistochemistry were technically less exacting. CONCLUSION: These findings support the application of M30 immunoreactivity in the study of apoptosis.

Mitotic and in situ end-labeling apoptotic indices as prognostic markers in malignant mesothelioma.

The prognostic role of mitotic and apoptotic indices in 60 patients with malignant mesothelioma was examined on hematoxylin-eosin-stained sections. The findings were compared with apoptotic indices determined by in situ end labeling (ISEL) in 35 of the cases. There was a significant survival advantage associated with lower mitotic counts and a lower apoptotic index defined by ISEL (P < .05). There was no association between the apoptotic index derived from the hematoxylin-eosin-stained sections and prognosis (P = .90). However, there was a positive association between the apoptotic counts calculated from hematoxylin-eosin- and ISEL-stained sections (P < .01). The mitotic count and ISEL apoptotic index are potentially useful markers of prognosis in malignant mesothelioma.

Acinar morphology in colorectal cancer is associated with survival but is not an independent prognostic variable.

AIMS: Microacinar morphology has been reported as a stage-independent prognostic variable for colorectal cancer. We have undertaken a retrospective analysis to test this observation in patients with colonic as well as rectal adenocarcinoma, and to assess interobserver agreement for identifying microacinar morphology. METHODS AND RESULTS: One hundred and eighty patients with colorectal cancer, 144 colonic and 36 rectal, were assigned to either macroacinar (144) or microacinar (36) groups. There was excellent correlation between two observers examining the colorectal cancers independently (kappa statistic, kappa = 0.87). Patients with microacinar tumours had a significantly reduced median survival compared with macroacinar lesions (46 and 87 months, respectively, P = 0.022) and this morphology was significantly associated with higher Dukes' stage (P = 0.007). Microacinar morphology lacked statistical significance when examined in a multivariate analysis with other prognostic variables, both when colonic and rectal tumours were examined either separately or as a combined colorectal group, but small numbers of rectal tumours in this study make it difficult to draw useful conclusions about microacinar morphology in rectal adenocarcinoma. CONCLUSIONS: Microacinar morphology was strongly associated with poor prognosis when examined in isolation but was not found to be an independent factor when examined with other prognostic variables.