Christopher Henderson

PTEN mutations are common in sporadic microsatellite stable colorectal cancer.

The tumour suppressor gene PTEN, located at chromosome sub-band 10q23.3, encodes a dual-specificity phosphatase that negatively regulates the phosphatidylinositol 3′-kinase (PI3 K)/Akt-dependent cellular survival pathway. PTEN is frequently inactivated in many tumour types including glioblastoma, prostate and endometrial cancers. While initial studies reported that PTEN gene mutations were rare in colorectal cancer, more recent reports have shown an approximate 18% incidence of somatic PTEN mutations in colorectal tumours exhibiting microsatellite instability (MSI+). To verify the role of this gene in colorectal tumorigenesis, we analysed paired normal and tumour DNA from 41 unselected primary sporadic colorectal cancers for PTEN inactivation by mutation and/or allelic loss. We now report PTEN gene mutations in 19.5% (8/41) of tumours and allele loss, including all or part of the PTEN gene, in a further 17% (7/41) of the cases. Both PTEN alleles were affected in over half (9/15) of these cases showing PTEN genetic abnormalities. Using immunohistochemistry, we have further shown that all tumours harbouring PTEN alterations have either reduced or absent PTEN expression and this correlated strongly with later clinical stage of tumour at presentation (P=0.02). In contrast to previous reports, all but one of the tumours with PTEN gene mutations were microsatellite stable (MSI−), suggesting that PTEN is involved in a distinct pathway of colorectal tumorigenesis that is separate from the pathway of mismatch repair deficiency. This work therefore establishes the importance of PTEN in primary sporadic colorectal cancer.

Serous oligocystic adenoma of the pancreas: a clinicopathological and immunohistochemical study of three cases with ultrastructural findings

Aims: Serous oligocystic adenoma of the pancreas is an uncommon benign neoplasm and is a recently described entity. To date, there are 19 adult cases of this tumour. We report three additional cases, two with macrocystic and one with unilocular types. We describe their clinicopathological, immunohistochemical and ultrastructural findings and review the worlds literature. Methods: For a 10‐year period, we reviewed all benign cystic lesions of the pancreas with emphasis on serous oligocystic adenoma. We characterised serous oligocystic adenoma as an ill‐demarcated or encapsulated mass, composed largely or exclusively of macrocysts (cysts measuring 20 mm or more) but few in number (oligolocular). Grossly, it may contain only a single cyst (unilocular) of any size with a few satellite cysts observed on histological examination. Special stains and immunohistochemistry as well as electron microscopy were performed on three and two cases of serous oligocystic adenoma, respectively. Results: Between 1990 and 2000, we collected 26 benign cystic lesions of the pancreas, three of which were serous oligocystic adenomas (two with macrocystic and one with unilocular types). Many of the cells lining the cysts showed PAS positivity. There was negative staining for PAS with diastase digestion, Alcian blue and mucicarmine. All cases showed positive staining for CAM5.2, AE1/AE3, EMA and CK7. The proliferation index marker was low. There was negative staining for CK20, insulin, glucagon, somatostatin, synaptophysin, chromogranin A, CEA and p53. Ultrastructural studies on two cases revealed similar findings. The single row of uniform epithelial cells lining the cysts was composed of simple cuboidal to flat cells which rested on a thin basal lamina. Their nuclei were round to ovoid. Glycogen granules were identified in the cytoplasm. Short microvilli emerged from the epithelial apical surface. Adjacent tumour cells were connected by microfilaments. Conclusions: Serous oligocystic adenomas of the pancreas are uncommon benign tumours. Prior to this study, 19 adults with these lesions were reported in the worlds literature. No correct pre‐operative diagnosis was carried out on all 22 cases. The 20 patients with follow‐up ranging from 2 months to 5 years did not show tumour recurrence or malignant transformation.

Loss of special AT-rich sequence-binding protein 1 (SATB1) predicts poor survival in patients with colorectal cancer

Special AT‐rich sequence‐binding protein 1 (SATB1) is a cell type‐specific matrix attachment region binding protein, functioning as a global genome organizer. This study aims to investigate the expression pattern and the prognostic value of SATB1 in colorectal cancer.

Predictive and prognostic biomarkers for neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Locally advanced rectal cancer is regularly treated with trimodality therapy consisting of neoadjuvant chemoradiation, surgery and adjuvant chemotherapy. There is a need for biomarkers to assess treatment response, and aid in stratification of patient risk to adapt and personalise components of the therapy. Currently, pathological stage and tumour regression grade are used to assess response. Experimental markers include proteins involved in cell proliferation, apoptosis, angiogenesis, the epithelial to mesenchymal transition and microsatellite instability. As yet, no single marker is sufficiently robust to have clinical utility. Microarrays that screen a tumour for multiple promising candidate markers, gene expression and microRNA profiling will likely have higher yield and it is expected that a combination or panel of markers would prove most useful. Moving forward, utilising serial samples of circulating tumour cells or circulating nucleic acids can potentially allow us to demonstrate tumour heterogeneity, document mutational changes and subsequently measure treatment response.

Surgical management of colorectal cancer in south-western Sydney 1997−2001: a prospective series of 1293 unselected cases from six public hospitals

Background:  The aim of the present study is to provide local data for the management of colorectal cancers in the south‐western Sydney health area from 1997 to 2001.

Direct tumor invasion in colon cancer: correlation with tumor spread and survival.

PurposeThis study examined the correlation between depth of local invasion in colon cancer and tumor spread and patient survival.MethodsA cohort of 796 patients with a complete set of TNM staging information following an elective resection for colon cancer was selected. The rates of lymph node and distant metastasis, tumor differentiation, and extramural venous invasion for different tumor (T) categories were compared. The effects of initial tumor (T) category on overall patient survival were studied.ResultsThe depth of local tumor invasion correlated strongly with nodal involvement (P = 0.0001), rates of extramural venous invasion (P = 0.0002), poor differentiation (P = 0.0001), and distant metastasis (P = 0.0001). Fifty-seven percent of the patients remained lymph node-negative and distant metastasis-negative irrespective of their depth of tumor invasion had no impact on overall survival (P = 0.49). For patients with lymph node or distant metastasis (43 percent), depth of tumor invasion had significant impact on overall survival (P = 0.001). Thirteen percent of T3N1, 33 percent of T3N2, 40 percent of T4N1, and 68.percent of T4N2 cases had distant metastasis at presentation.ConclusionTwo types of colon cancer were observed: locally active and tendency to metastasize. For the latter, overall mortality and the risk of metastasis increased with depth of tumor invasion.

Cryptococcosis presenting as upper limb cellulitis and ulceration: a case series.

We report four cases of cryptococcosis presenting as upper limb cellulitis or ulceration, or both. Three of the four patients were on long‐term prednisolone therapy at the time of presentation. In each case, the diagnosis of cryptococcosis was established by a biopsy of the skin. Only one of the four patients had conclusive evidence of disseminated disease. Our cases highlight the importance of skin biopsy in immunosuppressed individuals presenting with cellulitis, particularly when the cellulitis occurs in an atypical location and when the clinical condition fails to respond to standard antibacterial therapy.

Cutaneous crystal storing histiocytosis: a report of two cases

Crystal storing histiocytosis (CSH) is a rare condition where crystals accumulate in the cytoplasm of macrophages and is usually associated with a lymphoplasmacytic neoplasm producing a monoclonal immunoglobulin with kappa light chain. CSH with primary manifestation in the skin is extraordinarily rare and limited to four case reports in the literature. Here we present two cases of cutaneous CSH. One case is that of an 80 year old woman who presented with bilateral periorbital oedema with yellow discolouration. Skin biopsy showed dermal CSH in association with a neoplastic lymphoplasmacytoid infiltrate showing IgM kappa light chain restriction. Subsequent work up led to the discovery of Waldenstroms macroglobulinemia. She had an indolent clinical course but died 6 years later from transformation into a diffuse large B cell lymphoma in the bone marrow. The other case is that of a 52 year old man who was recently diagnosed with multiple myeloma and developed a pruritic rash on his back during chemotherapy. Skin biopsy showed Grover disease (transient acantholytic dermatosis) and crystal storing macrophages in the superficial dermis. He died 4 years later after a protracted clinical course involving multiple cycles of chemotherapy and numerous complications. In both patients cutaneous CSH occurred early in the course of their lymphoplasmacytic malignancy and its development did not herald rapid clinical decline.

Primary melanotic psammomatous schwannoma of the trachea

d There will be some doubt as to whether records are complete or relatives are honest about clinical histories. d It is not always possible to speculate on all of the risk factors; for example, because of the religious and sociocultural barriers, we could not take an accurate history of homosexuality, prostitution, sexual promiscuity, etc. d Many forensic autopsies initially have little or unknown medical or social history. It is only later that the necessary information becomes available as to the possibility of the level of risk of infection. d The lack of a known history of a risk factor does not equate with absence of the risk factor.

Suppurative cribriform ulcers in one leg

Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia, Department of Anatomical Pathology, Sydney South West Pathology, Liverpool Hospital, Sydney, NSW, Australia, School of Medical Sciences, Faculty of Medicine, University of New South Wales, NSW, Australia, School of Medicine, University of Western Sydney, NSW, Australia, Department of Dermatology, Liverpool Hospital, Sydney, NSW, Australia, Centenary Institute, Newtown, NSW, Australia, and Discipline of Dermatology, University of Sydney, Sydney, NSW, Australia