We report a case of pleural malignant melanoma (MM) in a 26year-old European female. A chest X-ra... more We report a case of pleural malignant melanoma (MM) in a 26year-old European female. A chest X-ray for asymptomatic immigration screening demonstrated an incidental right apical opacity. Her only medical history was a pigmented neck lesion, at age 11, that spontaneously regressed. Computed tomography (CT) scan revealed multiple pleural lesions in the right hemithorax, the largest at the apex measuring 60 mm. CT-positron emission tomography showed a thin peripheral rim of increased uptake in the apical lesion and mild avidity in the other nodules. CT-guided biopsy demonstrated a collagenous matrix with an infiltrate of cells containing melanin. Surgical resection was recommended at our multidisciplinary meeting. A posterolateral thoracotomy was performed. Multiple dark nodules were visualized across the pleura (Fig. 1a). The large apical mass was resected (Fig. 1b) and the remaining nodules were removed with a radical pleurectomy. Histopathology of all nodules was consistent with MM. Given the unclear history of the pigmented neck lesion, it is indeterminate whether this was primary or secondary. The patient had an uneventful post-operative recovery and sought further treatment overseas. Since being first described in 1978, only eight cases of primary pleural MM have been reported. Presentation is usually with respiratory symptoms or loss of weight. Pleural MM is hypothesized to arise from (i) migration of cutaneous nevus cells to the pleura via lymphatics, (ii) migration of melanoblasts to the pleura from the neural crest, (iii) areas of pleural squamous metaplasia or (iv) native pluripotent stem cells. The pleura is an unusual site for metastasis of MM, and in 70% of cases there are concurrent intrapulmonary metastases. Only three cases of isolated pleural metastases of MM, without the involvement of other organs, have been reported. Both primary and secondary pleural MMs are managed with chemotherapy, with or without surgical debulking. Despite treatment, prognosis is poor and most patients die within 1 year of diagnosis. Thus, MM is an important diagnosis to consider in the workup of a pleural mass.
Pulmonary complications are described in a case of Ehlers-Danlos syndrome type IV, established by... more Pulmonary complications are described in a case of Ehlers-Danlos syndrome type IV, established by studies of collagen biosynthesis. At age 20.5 years the patient, who had previously suffered a spontaneous colonic perforation, developed intermittent recurrent hemoptysis and had a spontaneous hemopneumothorax. At presentation, imaging studies revealed multiple scattered cavitary lesions in both lungs. On separate occasions large parenchymal cysts ensued and subsequently regressed. Reviews of other reported patients indicate that pulmonary complications do occur in patients with Ehlers-Danlos syndrome type IV but have not resulted directly in patient mortality.
Medullary carcinoma is a recently described subtype of mismatch repair deficient (MMRd) colorecta... more Medullary carcinoma is a recently described subtype of mismatch repair deficient (MMRd) colorectal carcinoma (CRC) which, despite being poorly differentiated by traditional morphological criteria, has been reported to have a good prognosis. We investigated the pathological and clinical features of medullary CRC in an unselected cohort of CRCs undergoing surgical resection. All CRCs resected within a single health district database from 1998 to 2012 were categorized prospectively and underwent retrospective review to identify 91 medullary CRCs, with 11 additional cases from 2013 to 2014. Strict criteria were employed to diagnose medullary carcinoma requiring both MMRd and greater than 90 % of the tumor to demonstrate typical morphology, including solid growth. The demographic and pathological features, as well as all-cause survival, were compared with other CRCs, and specifically to other MMRd CRCs. From 1998 to 2012, 91 of 3,295 CRCs (2.8 %) were of the medullary type. Medullary CRC was more likely to arise in females than males (3.3:1; p < 0.0001), the elderly (mean age 77 vs. 71 years; p < 0.001), and the right colon (86 %; p < 0.0001). All medullary CRCs demonstrated MMR deficiency (considered an inclusion criteria) and 86 % were BRAFV600E-mutated (p < 0.0001). Thirty-day mortality after resection was higher in medullary CRC (4.6 vs. 1.7 %; p = 0.049). On univariate analysis, survival was not better than well-differentiated or other MMRd tumors. However, using a multivariate model, a medullary phenotype was protective (hazard ratio of death 0.54, 95 % CI 0.30-0.96; p = 0.037). Medullary CRC is more common than previously reported, frequently presents with locally advanced disease, and may be associated with higher mortality at 30 days after resection. Despite this, when strict criteria are used for diagnosis, the overall survival is favorable when compared with CRCs with equivalent demographic and pathological characteristics.
Mutation specific immunohistochemistry (IHC) is a promising new technique to detect the presence ... more Mutation specific immunohistochemistry (IHC) is a promising new technique to detect the presence of the BRAFV600E mutation in colorectal carcinoma (CRC). When performed in conjunction with mismatch repair (MMR) IHC, BRAFV600E IHC can help to further triage genetic testing for Lynch Syndrome. In a cohort of 1426 patients undergoing surgery from 2004 to 2009 we recently demonstrated that the combination of MMR and BRAFV600E IHC holds promise as a prognostic marker in CRC, particularly because of its ability to identify the poor prognosis MMR proficient (MMRp) BRAFV600E mutant subgroup. We attempted to validate combined MMR and BRAFV600E IHC as a prognostic indicator in a separate cohort comprising consecutive CRC patients undergoing surgery from 1998 to 2003. IHC was performed on a tissue microarray containing tissue from 1109 patients with CRC. The 5 year survivals stratified by staining patterns were: MMRd/BRAFwt 64%, MMRd/ BRAFV600E 64%, MMRp/BRAFwt 60% and MMRp/BRAFV600E 53%. Using the poor prognosis MMRp/BRAFV600E phenotype as baseline, univariate Cox regression modelling demonstrated the following hazard ratios for death: MMRd/BRAFwt HR = 0.71 (95%CI = 0.40-1.27), p = 0.31; MMRd/BRAFV600E HR = 0.74 (95%CI = 0.51-1.07), p = 0.11 and MMRp/BRAFwt HR = 0.79 (95%CI = 0.60-1.04), p = 0.09. Although the findings did not reach statistical significance, this study supports the potential role of combined MMR and BRAF IHC as prognostic markers in CRC.
Pulmonary complications are described in a case of Ehlers-Danlos syndrome type IV, established by... more Pulmonary complications are described in a case of Ehlers-Danlos syndrome type IV, established by studies of collagen biosynthesis. At age 20.5 years the patient, who had previously suffered a spontaneous colonic perforation, developed intermittent recurrent hemoptysis and had a spontaneous hemopneumothorax. At presentation, imaging studies revealed multiple scattered cavitary lesions in both lungs. On separate occasions large parenchymal cysts ensued and subsequently regressed. Reviews of other reported patients indicate that pulmonary complications do occur in patients with Ehlers-Danlos syndrome type IV but have not resulted directly in patient mortality.
We report a case of pleural malignant melanoma (MM) in a 26year-old European female. A chest X-ra... more We report a case of pleural malignant melanoma (MM) in a 26year-old European female. A chest X-ray for asymptomatic immigration screening demonstrated an incidental right apical opacity. Her only medical history was a pigmented neck lesion, at age 11, that spontaneously regressed. Computed tomography (CT) scan revealed multiple pleural lesions in the right hemithorax, the largest at the apex measuring 60 mm. CT-positron emission tomography showed a thin peripheral rim of increased uptake in the apical lesion and mild avidity in the other nodules. CT-guided biopsy demonstrated a collagenous matrix with an infiltrate of cells containing melanin. Surgical resection was recommended at our multidisciplinary meeting. A posterolateral thoracotomy was performed. Multiple dark nodules were visualized across the pleura (Fig. 1a). The large apical mass was resected (Fig. 1b) and the remaining nodules were removed with a radical pleurectomy. Histopathology of all nodules was consistent with MM. Given the unclear history of the pigmented neck lesion, it is indeterminate whether this was primary or secondary. The patient had an uneventful post-operative recovery and sought further treatment overseas. Since being first described in 1978, only eight cases of primary pleural MM have been reported. Presentation is usually with respiratory symptoms or loss of weight. Pleural MM is hypothesized to arise from (i) migration of cutaneous nevus cells to the pleura via lymphatics, (ii) migration of melanoblasts to the pleura from the neural crest, (iii) areas of pleural squamous metaplasia or (iv) native pluripotent stem cells. The pleura is an unusual site for metastasis of MM, and in 70% of cases there are concurrent intrapulmonary metastases. Only three cases of isolated pleural metastases of MM, without the involvement of other organs, have been reported. Both primary and secondary pleural MMs are managed with chemotherapy, with or without surgical debulking. Despite treatment, prognosis is poor and most patients die within 1 year of diagnosis. Thus, MM is an important diagnosis to consider in the workup of a pleural mass.
Pulmonary complications are described in a case of Ehlers-Danlos syndrome type IV, established by... more Pulmonary complications are described in a case of Ehlers-Danlos syndrome type IV, established by studies of collagen biosynthesis. At age 20.5 years the patient, who had previously suffered a spontaneous colonic perforation, developed intermittent recurrent hemoptysis and had a spontaneous hemopneumothorax. At presentation, imaging studies revealed multiple scattered cavitary lesions in both lungs. On separate occasions large parenchymal cysts ensued and subsequently regressed. Reviews of other reported patients indicate that pulmonary complications do occur in patients with Ehlers-Danlos syndrome type IV but have not resulted directly in patient mortality.
Medullary carcinoma is a recently described subtype of mismatch repair deficient (MMRd) colorecta... more Medullary carcinoma is a recently described subtype of mismatch repair deficient (MMRd) colorectal carcinoma (CRC) which, despite being poorly differentiated by traditional morphological criteria, has been reported to have a good prognosis. We investigated the pathological and clinical features of medullary CRC in an unselected cohort of CRCs undergoing surgical resection. All CRCs resected within a single health district database from 1998 to 2012 were categorized prospectively and underwent retrospective review to identify 91 medullary CRCs, with 11 additional cases from 2013 to 2014. Strict criteria were employed to diagnose medullary carcinoma requiring both MMRd and greater than 90 % of the tumor to demonstrate typical morphology, including solid growth. The demographic and pathological features, as well as all-cause survival, were compared with other CRCs, and specifically to other MMRd CRCs. From 1998 to 2012, 91 of 3,295 CRCs (2.8 %) were of the medullary type. Medullary CRC was more likely to arise in females than males (3.3:1; p < 0.0001), the elderly (mean age 77 vs. 71 years; p < 0.001), and the right colon (86 %; p < 0.0001). All medullary CRCs demonstrated MMR deficiency (considered an inclusion criteria) and 86 % were BRAFV600E-mutated (p < 0.0001). Thirty-day mortality after resection was higher in medullary CRC (4.6 vs. 1.7 %; p = 0.049). On univariate analysis, survival was not better than well-differentiated or other MMRd tumors. However, using a multivariate model, a medullary phenotype was protective (hazard ratio of death 0.54, 95 % CI 0.30-0.96; p = 0.037). Medullary CRC is more common than previously reported, frequently presents with locally advanced disease, and may be associated with higher mortality at 30 days after resection. Despite this, when strict criteria are used for diagnosis, the overall survival is favorable when compared with CRCs with equivalent demographic and pathological characteristics.
Mutation specific immunohistochemistry (IHC) is a promising new technique to detect the presence ... more Mutation specific immunohistochemistry (IHC) is a promising new technique to detect the presence of the BRAFV600E mutation in colorectal carcinoma (CRC). When performed in conjunction with mismatch repair (MMR) IHC, BRAFV600E IHC can help to further triage genetic testing for Lynch Syndrome. In a cohort of 1426 patients undergoing surgery from 2004 to 2009 we recently demonstrated that the combination of MMR and BRAFV600E IHC holds promise as a prognostic marker in CRC, particularly because of its ability to identify the poor prognosis MMR proficient (MMRp) BRAFV600E mutant subgroup. We attempted to validate combined MMR and BRAFV600E IHC as a prognostic indicator in a separate cohort comprising consecutive CRC patients undergoing surgery from 1998 to 2003. IHC was performed on a tissue microarray containing tissue from 1109 patients with CRC. The 5 year survivals stratified by staining patterns were: MMRd/BRAFwt 64%, MMRd/ BRAFV600E 64%, MMRp/BRAFwt 60% and MMRp/BRAFV600E 53%. Using the poor prognosis MMRp/BRAFV600E phenotype as baseline, univariate Cox regression modelling demonstrated the following hazard ratios for death: MMRd/BRAFwt HR = 0.71 (95%CI = 0.40-1.27), p = 0.31; MMRd/BRAFV600E HR = 0.74 (95%CI = 0.51-1.07), p = 0.11 and MMRp/BRAFwt HR = 0.79 (95%CI = 0.60-1.04), p = 0.09. Although the findings did not reach statistical significance, this study supports the potential role of combined MMR and BRAF IHC as prognostic markers in CRC.
Pulmonary complications are described in a case of Ehlers-Danlos syndrome type IV, established by... more Pulmonary complications are described in a case of Ehlers-Danlos syndrome type IV, established by studies of collagen biosynthesis. At age 20.5 years the patient, who had previously suffered a spontaneous colonic perforation, developed intermittent recurrent hemoptysis and had a spontaneous hemopneumothorax. At presentation, imaging studies revealed multiple scattered cavitary lesions in both lungs. On separate occasions large parenchymal cysts ensued and subsequently regressed. Reviews of other reported patients indicate that pulmonary complications do occur in patients with Ehlers-Danlos syndrome type IV but have not resulted directly in patient mortality.
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Papers by Stuart Pincott