Lack of correlation between MSH3 immunohistochemistry and microsatellite analysis for the detection of elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in colorectal cancers.

Immunohistochemical evaluation of mismatch repair protein (MMR) expression is an important screening tool in diagnostic pathology, where it is routinely used to identify subsets of colorectal cancers (CRCs) with either inherited or sporadic forms of microsatellite instability (MSI). MSH3 is not included in current MMR panels, although aberrant MSH3 expression is reported to occur in 40-60% of CRCs and is associated with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) and a worse prognosis. In this study, we applied MSH3 immunohistochemistry and tetranucleotide MSI analysis to a cohort of 250 unselected CRCs to evaluate the potential use of the methods in routine practice. Partial, complete, and focal loss of nuclear MSH3 and its cytoplasmic mislocalization were evident in 67% of tumors, whereas MSI was evident in two to six of a panel of six tetranucleotide repeats in 46% of cases. However, concordance between MSH3 immunohistochemistry and tetranucleotide MSI results was only 61%, indicating the unsuitability of this combination of tests in routine pathology practice. MSH3 immunostaining was compromised in areas of tissue crush and autolysis, which are common in biopsy and surgical samples, potentially mitigating against its routine use. Although tetranucleotide MSI is clearly evident in a subset of CRCs, further development of validated sets of tetranucleotide repeats and either MSH3 or other immunohistochemical markers will be required to include EMAST testing in the routine evaluation of CRCs in clinical practice.

Uterine plexiform tumourlets: multifocal and solitary cases with subsets expressing melanocytic markers.

AIMS: Uterine plexiform tumourlets are traditionally regarded as microscopic epithelioid leiomyomas. They are typically solitary incidental findings, but may be multifocal (plexiform leiomyomatosis). We aim to report novel immunohistochemical and morphological findings, specifically the presence of spindled and epithelioid cell nodules, in these lesions. METHODS AND RESULTS: Three cases of plexiform leiomyomatosis and 16 solitary plexiform tumourlets were included. Two cases of plexiform leiomyomatosis and four solitary plexiform tumourlets demonstrated spindled and epithelioid cell nodules which, in one of the former cases, formed expansile masses up to 15 mm. The nodules demonstrated mild cytological atypia and occasional mitotic activity, and they were associated with a myxoid stroma and a lymphohistiocytic infiltrate which imparted a granulomatous appearance to the microscopic lesions. The plexiform tumourlets (solitary and multifocal) consistently expressed desmin, smooth muscle actin, ER and PR, and they commonly co-expressed melanocytic and perivascular epithelioid cell (PEC) markers HMB45, MiTF and cathepsin K. The spindled and epithelioid cell nodules were generally negative for myoid markers and hormone receptors, but expressed p16, cyclin D1 and TFE3. All lesions tested were negative for cytokeratin, S100, melanA, inhibin, EMA, ALK and BCOR; fluorescence in-situ hybridisation was negative for ALK, TFE3 and BCOR rearrangements in one of the larger spindled and epithelioid cell nodules. CONCLUSIONS: Plexiform tumourlets commonly co-express myoid and melanocytic markers and may represent part of the spectrum of gynaecological PEC-related lesions. Some cases are associated with spindled and epithelioid cell nodules that could potentially mimic other uterine myxoid neoplasms.

Histiocytoid Melanoma.

While most melanomas display well-characterised and readily recognised architectural and cytomorphological features, unusual variants can create diagnostic difficulties. Variants which mimic benign or reactive processes are particularly problematic. We report 5 cases of melanoma characterised by a subtle microscopic appearance reminiscent of a benign dermal histiocytic infiltrate, which we refer to as "histiocytoid melanoma." These lesions are characterised clinically by ill-defined areas of cutaneous pigmentation, which in several cases reached large proportions. Microscopically, there is a subtle interstitial pattern of infiltration by predominantly single cells with a histiocytoid morphology, often resembling melanophages. Immunohistochemical confirmation was typically required, with the cells showing positive labelling for Sox-10 as well as Melan-A. In several examples, the proliferation extended to clinically uninvolved surgical margins, necessitating multiple excisions, and many of our patients have experienced locoregional recurrence. However, none have developed distant metastases or died of melanoma. While uncommon, this subtle variant is important to recognise in order to ensure adequate histological clearance is obtained.

Successful treatment of renal allograft and bladder malakoplakia with minimization of immunosuppression and prolonged antibiotic therapy.

Malakoplakia is an unusual granulomatous inflammatory disorder associated with diminished bactericidal action of leucocytes that occurs in immunosuppressed hosts. Cases of renal allograft malakoplakia are generally associated with a poor graft and patient survival. We present the case of a 56-year-old female with allograft and bladder malakoplakia occurring two years after renal transplantation complicated by an early antibody mediated rejection. Following a number of symptomatic urinary tract infections caused by resistant Gram-negative bacilli, a diagnosis of malakoplakia was made by biopsy of a new mass lesion of the renal allograft. Cystoscopy also revealed malakoplakia of the bladder wall. Immunosuppressant regimen was modified. Mycophenolate mofetil was ceased, prednisolone reduced to 5 mg/day and tacrolimus concentrations were carefully monitored to maintain trough serum concentrations of 2-4 µg/L. Concurrently, she received a prolonged course of intravenous antibiotics followed by 13 months of dual oral antibiotic therapy with fosfomycin and faropenem. This joint approach resulted in almost complete resolution of allograft malakoplakia lesions and sustained regression of bladder lesions on cystoscopy with histological resolution in bladder lesions. Her renal function has remained stable throughout the illness. If treated with sustained antimicrobial therapy and reduction of immunosuppression, cases of allograft malakoplakia may not necessarily be associated with poor graft survival.

Electrolysis - a new method of renal ablation?

OBJECTIVE: • To present a novel method of renal ablation using direct current electrolysis, using a porcine model to assess the safety and efficacy of the technique. MATERIALS AND METHODS: • In all, 20 anaesthetised pigs were used, after receiving ethical approval. The pigs were housed and managed in accordance with Institute of Medical and Veterinary Science guidelines. • A single 6 F catheter incorporating cathode and anode was inserted directly into the renal parenchyma via a loin incision. A direct current of 100 mA was applied for varying times. • Several treatments were performed in each pig and a total of 72 treatments were analysed. • The pigs were recovered and observed for 3 days with an analysis of electrolytes and creatinine after ablation. The pigs were humanely killed at 3 days and the kidneys submitted for histological analysis. RESULTS: • Complete tissue destruction was seen in the area of kidney treated with no viable cells. • A sharp line of demarcation was noted between normal renal parenchyma and the area of coagulative necrosis. The area of tissue ablation was reliably predicted from the duration of application of the electrolytic current. • One pig developed a secondary haemorrhage. CONCLUSIONS: • Renal electrolysis is a new method of focal renal ablation. The procedure may be carried out using a fine ablation catheter (6 F) allowing for the development of minimal intervention treatment of small renal masses. • This study shows the technique to be effective and safe. As with other renal ablative techniques there is a small risk of postoperative haemorrhage.

Isolated left atrial amyloidosis: acute premitral stenosis secondary to spontaneous intramural left atrial hemorrhagic dissection.

This case presentation describes the very rare condition of isolated atrial amyloidosis and it's associated complications. A 53-year-old male presented to hospital in severe pulmonary edema secondary to spontaneous intramural left atrial hemorrhage and subsequent wall dissection causing acute "pre-mitral valve" obstruction. The patient was subsequently found to have AL subtype amyloid, which has never before been reported in isolated atrial amyloidosis. The prognosis is poor in AL type amyloidosis with cardiac involvement.

The use of a "liquid" electrode in hepatic electrolysis.

BACKGROUND: The use of direct current electrolysis as a local nonthermal ablative technique for colorectal liver metastases promises to be a simple, safe, and effective therapy. Under general anesthesia, electrolysis is presently limited to tumors smaller than 5 cm, due to the protracted nature of its administration. In an attempt to enhance the effect of electrolysis, a direct current was passed through a preinjected bolus of acetic acid. METHODS: The effect of a combination of electrolysis and an injection of acetic acid was tested in the liver of eight normal pigs. The volumes of necrosis caused were analyzed. RESULTS: Acetic acid independently produced a volume of necrosis but did not provide a volumetric or rate advantage when used in combination with a direct current. Statistically, the only main effect on the volume of necrosis was a result of electrolysis. CONCLUSION: The use of 50% acetic acid to augment the efficacy of direct current electrolysis cannot be recommended.

Liver electrolysis: pH can reliably monitor the extent of hepatic ablation in pigs.

Electrolysis is a method of tissue ablation that creates chemical species and a pH gradient in response to direct current. Initial studies of electrolysis in animal models and humans have shown that it is a safe, predictable and effective process for destroying normal and tumour-bearing liver in a linear, dose-dependent manner. Presently, the amount of current that is applied (in coulombs) has to be calculated using historical data, with inherent inaccuracy. The present study tested whether pH could be used as a real-time monitor in order to predict more accurately the extent of necrosis. A total of 70 electrolytic lesions were created in 14 pigs, with pH monitoring of the lesion edge. The normal range of pH values was 6.5-8.7. A pH of less than 6 (at the anode) or more than 9 (at the cathode) reflected total cellular necrosis. When a pH value was recorded between 6.0 and 6.5 at the anode or between 8.7 and 9.0 at the cathode, the presence of necrosis was variable. In conclusion, during electrolytic ablation, pH measurement can monitor the extent of the induced necrosis.