Roderick Simpson - Academia.edu (original) (raw)

Papers by Roderick Simpson

Current Oncology, Feb 1, 2016

Objectives Adenoid cystic carcinoma (acc) is often treated with surgery, with or without adjuvant... more Objectives Adenoid cystic carcinoma (acc) is often treated with surgery, with or without adjuvant radiation therapy (rt). We evaluated disease characteristics, treatments, and potentially prognostic variables in patients with acc. Methods Our retrospective analysis considered consecutive cases of acc presenting at a tertiary care hospital between 2000 and 2014. Factors predictive of overall survival (os) and disease-free survival (dfs) were identified by univariate analysis. Results The 60 patients analyzed had a mean age of 58 years (range: 22-88 years), with a 2:1 female:male ratio. Tumour locations included the major salivary glands (40% parotid, 17% submandibular and sublingual), the oro-nasopharyngeal cavity (27%), and other locations (16%). Of the 60 patients, 35 (58%) received surgery with adjuvant rt; 12 (20%), rt only; 13 (22%), surgery only. Of 18 patients (30%) who experienced a recurrence within 5 years, 3 (5%) developed local recurrence only, and the remaining 15 (25%), distant metastasis. The 5-year os and dfs were 64.5% [95% confidence interval (ci): 45.9% to 78.1%] and 46.2% (95% ci: 29.7% to 61.2%) respectively. In patients without recurrence, 5-year os was 77% (95% ci: 52.8% to 89.9%), and in patients with recurrence, it was 42.7% (95% ci: 15.8% to 67.6%). Patients treated with rt only had a 5-year os of 9.2%. Predictors of 5-year dfs were TNM stage, T stage, nodal status, treatment received, and margin status; age, nodal status, treatment received, and margin status predicted 5-year os. Conclusions Despite surgery and rt, one third of patients with acc experience distant recurrence. Patients whose tumours are not amenable to surgery have a poor prognosis, indicating a need for alternative approaches to improve outcomes.

Histopathology, Mar 1, 1991

Salivary duct adenocarcinoma Six cases of salivary duct adenocarcinoma are presented. All had a h... more Salivary duct adenocarcinoma Six cases of salivary duct adenocarcinoma are presented. All had a history of a rapidly enlarging mass in the parotid gland with involvement of the facial nerve. The histopathological appearance was distinctive, each case showing an invasive tumour resembling ductal carcinoma of the breast, often with areas of comedo necrosis. Five patients died within 26 months, and the one long-term survivor (68 months) has widespread metastatic disease. These findings are similar to cases which have previously been described, but the tumour has not been widely reported, particularly in Britain. We feel that salivary duct adenocarcinoma is a distinct clinicopathological entity and, as its histological appearance is usually unmistakable, we believe it deserves wider recognition.

Journal of Clinical Pathology, May 1, 1991

Four cases of epithelial-myoepithelial carcinoma of the salivary glands arose as painless masses ... more Four cases of epithelial-myoepithelial carcinoma of the salivary glands arose as painless masses in patients over 60 years old, three in the parotid and one in the submandibular gland. Histologically, all the tumours were composed of small ducts with a-double cell lining surrounded by a basement membrane. The inner cells were epithelial and the outer cells myoepithelial, the latter usually possessing clear cytoplasm. There was a variable degree of intervening hyalinised stroma. All the tumours were partly encapsulated, but also displayed local invasiveness. One of the tumours also showed areas of dedifferentiation when it later recurred and metastasised. The other three were apparently cured by initial excision, with adjuvant radiotherapy in one instance. In the past this tumour has been described as clear cell adenoma, and it was only recently that its true malignant nature, albeit low grade, was recognised. Reports of epithelial-myoepithelial carcinoma are still relatively few, with only one case described from Britain. It is recommended that this histologically distinct neoplasm deserves wider recognition.

British Journal of Plastic Surgery, 1996

Virchows Archiv, Jan 14, 2022

This review gives a brief history of the development of head and neck pathology in Europe from a ... more This review gives a brief history of the development of head and neck pathology in Europe from a humble beginning in the 1930s to the explosive activities the last 15 years. During the decades before the introduction of immunohistochemistry in the 1980s, head and neck pathology grew as a subspeciality in many European countries. In the late 1940s, the Institute of Laryngology and Otology with its own pathology laboratory was founded in London, and in 1964 the World Health Organization (WHO) International Reference Centre for the Histological Classification of Salivary Tumours was established at the Bland-Sutton Institute of Pathology, also in London. International collaboration, and very much so in Europe, led to the publication of the first WHO Classification of Salivary Gland Tumours in 1972. In the 1960s, a salivary gland register was organised in Hamburg and in Cologne the microlaryngoscopy was invented enabling microscopic endoscopic examination and rather shortly afterwards a carbon dioxide laser attached to the microscope became established and laryngeal lesions could be treated by laser vaporisation. During the last three decades, the use of immunohistochemistry supplemented with cytogenetic and refined molecular techniques has greatly facilitated the pathological diagnostics of head and neck lesions and has had a huge impact on research. Collaboration between different European centres has drastically increased partly due to establishment of scientific societies such as the Head and Neck Working Group (HNWG) within the European Society of Pathology and the International Head and Neck Scientific Group (IHNSG). A very large number of European pathologists have contributed to the 2nd, 3rd and 4th WHO books, and are involved in the upcoming 5th edition. Accredited educational meetings and courses are nowadays regularly arranged in Europe. Numerous textbooks on head and neck pathology have been written and edited by European pathologists. The increased collaboration has created larger series of tumours for research and new entities, mainly defined by their genetic abnormalities, are continuously emerging from Europe, particularly regarding salivary gland neoplasms and “undifferentiated” sinonasal tumours. These findings have led to a better and more precise classification and open the possibilities for new treatment strategies.

International Journal of Gynecological Pathology, Mar 1, 2011

Gliomatosis peritonei (GP) describes the implantation of mature neuroglial tissue in the peritone... more Gliomatosis peritonei (GP) describes the implantation of mature neuroglial tissue in the peritoneum and is usually associated with mature ovarian teratoma but is also found in cases of immature teratoma. We report the case of a patient with recurrent mature ovarian teratoma, GP, endometriosis (with malignant transformation), and carcinoid tumor, found at the time of hysterectomy for a primary endometrial adenocarcinoma. This unusual combination of tumor types has not been reported earlier. Metaplasia of the totipotential subcoelomic or submesothelial stem cells is a recognized pathway for the development of endometriosis. Evidence from molecular genetic studies suggests that a similar process of stem cell differentiation may explain at least some cases of GP. The coexistence (and colocalization) of endometriosis, GP, and carcinoid tumor in this case raises the possibility that peritoneal stem cells may occasionally show an even wider spectrum of aberrant differentiation. This has relevance for the assessment and management of patients with synchronous gynecologic tumors or presumed metastatic disease.

Annals of Diagnostic Pathology, Dec 1, 1997

Ossifying fibromyxoid tumor of soft parts is an unusual benign neoplasm, with a tendency for loca... more Ossifying fibromyxoid tumor of soft parts is an unusual benign neoplasm, with a tendency for local recurrence. Its typical microscopic appearance is that of a multinodular proliferation of round to spindle shaped cells separated by fibrous bands in which bone formation is often seen. Herein, we present the clinicopathologic features of 17 examples of this tumor with particular emphasis on some unusual histopathologic features that may place pitfalls in the diagnosis of this tumor, including satellite micronodules, mucinous microcysts, absence of myxoid areas, crush artifact, multiple microcalcifications, epidermoid cysts, atypical chondroid differentiation with binucleate lacunar cells, pericytic growth pattern, and malignant change. Awareness of these unusual morphologic features should lead to a search for areas displaying the more typical features of ossifying fibromyxoid tumor to arrive at a correct diagnosis.

The American Journal of Surgical Pathology, May 1, 1998

A 50-year-old woman had a malignant tumor of the left breast, which recurred twice, metastasized,... more A 50-year-old woman had a malignant tumor of the left breast, which recurred twice, metastasized, and caused death after 39 months. Histologically, the original neoplasm and the first recurrence comprised an adenomyoepithelioma, in addition to a sarcoma composed of trabeculae of mature and immature bone, osteoid, and partly calcified, dense collagenous tissue. The trabeculae were lined by alpha-smooth muscle actin-positive mononuclear tumor cells, which also extended into the stroma. Similarly, scattered osteoclastlike, multinucleate giant cells were present in the stroma and in the region of the trabeculae. This same pattern of adenomyoepithelioma and osteosarcoma also was seen in the last recurrence, together with a proliferation of undifferentiated malignant spindle-shaped cells. The last biopsy also contained a separate small focus of invasive ductal carcinoma of usual type. It was concluded that this, apparently unique, tumor probably represented an adenomyoepithelioma in which a metaplastic sarcoma of osteogenic and undifferentiated types developed from the myoepithelial element, and in which a carcinoma developed from the epithelial component.

Histopathology, Nov 1, 1999

Metaplastic (infarcted) Warthin's tumour of the parotid gland: a possible consequence of fine nee... more Metaplastic (infarcted) Warthin's tumour of the parotid gland: a possible consequence of fine needle aspiration biopsy Aims: The metaplastic (or infarcted) variant of Warthin's tumour is characterized by replacement of much of the original oncocytic epithelium by metaplastic squamous cells, along with areas of extensive necrosis, fibrosis and inflammatory change. The pathogenesis is unknown, but it is most likely to be vascular in origin. An association with a previous fine needle aspiration (FNA) has been suggested, and this is explored further. Methods and results: Nine metaplastic Warthin's tumours were collected from several centres: all arose in the parotid gland, and all showed the characteristic histological features. Eight had previously undergone FNA some 1-4 months before surgery; the other case had had an incisional biopsy. Conclusions: It is important to recognize metaplastic Warthin's tumour, because the differential diagnoses of this benign neoplasm include mucoepidermoid and squamous carcinoma, both primary and metastatic. The tumours in this study followed FNA or biopsy, and we believe this association is unlikely to be coincidental. Although many metaplastic Warthin's tumours clearly arise spontaneously, we conclude that the balance of probabilities favours the view that FNA is capable of causing metaplastic change in a Warthin's tumour, and may have done so in these cases. If so, this previously unusual subtype will become increasingly common, as FNA becomes more widely used (and its value appreciated) in the investigation of patients with a mass in the neck.

Acta cytologica

A 48-year-old woman presented with a long history of a lump in the breast, which was clinically d... more A 48-year-old woman presented with a long history of a lump in the breast, which was clinically diagnosed as a fibroadenoma. Cytologic examination of fluid aspirated intraoperatively demonstrated groups of carcinoma cells. Excision of the mass showed that this discrepancy was due to carcinoma within a fibro adenoma. Reports of such an occurrence are few, and none, to the best of our knowledge, has previously documented the cytologic findings.

Journal of the Neurological Sciences, Aug 1, 1985

ABSTRACT Nine areas of the brain from a case of adrenoleukodystrophy were examined histopathologi... more ABSTRACT Nine areas of the brain from a case of adrenoleukodystrophy were examined histopathologically and by gas chromatography for fatty acid content. The main findings were: (1) the degree of demyelination was related to the pentacosanoic and hexacosanoic to docosanoic acid ratios (C25:0/C22:0 and C26:0/C22:0); gliosis was related to the ratios of several fatty acids to docosanoic acid; (2) there was a shift towards smaller components (C22:0, C23:0, C24:0) of the saturated fatty acid series in the less affected areas, to larger components and various minor components in regions of active demyelination; (3) mainly saturated fatty acids of the middle class components (C24:0, C25:0 and C26:0) were found in severely affected areas where the active process is complete. Because a region of high long chain fatty acid content, lacking histopathological change, was detected, the hypothesis is presented that the primary event in childhood ALD is related to defective lipid metabolism and that this preceeds demyelination.

Current Diagnostic Pathology, Jun 1, 1997

Infiltration of the salivary glands by lymphocytes poses two major diagnostic problems: first, di... more Infiltration of the salivary glands by lymphocytes poses two major diagnostic problems: first, differentiating malignant lymphoma from reactive processes and second, separating autoimmune sialadenitis, which may progress to lymphoma from lesions lacking this implication. Non-autoimmune infiltrates characterize obstructive and infective diseases, several non-infective conditions and reactions to certain epithelial neoplasms. Autoimmunity plays a still poorly understood part in the pathogenesis of myoepithelial sialadenitis (MESA), a pathological entity frequently manifested as the clinical condition Sj6gren's syndrome. A proportion of MESA develop malignant lymphoma of mucosa-associated lymphoid tissue (MALT) type, and recent studies have allowed the early stages in the evolution to malignancy to be recognized. If possible, MALT lymphoma should also be distinguished from nodal lymphomas presenting in intraparotid lymph nodes which are biologically different and usually carry a worse prognosis. Salivary lymphoepithelial cystic lesions are a heterologous group including Warthin's tumour, benign lymphoepithelial cyst, MESA with dilated ducts, cystic lymphoid hyperplasia of AIDS, MALT lymphoma with dilated ducts, cystic mucoepidermoid carcinoma with a lymphocytic response, and cystic metastases in intraparotid lymph nodes.

Respiratory Medicine, Aug 1, 1993

IlltrOdUCtiOll Primary clear-cell carcinoma of the lung is defined as a malignant epithelial neop... more IlltrOdUCtiOll Primary clear-cell carcinoma of the lung is defined as a malignant epithelial neoplasm composed on histopathological examination largely of optically clear non-mucin producing cells without evidence of squamous differentiation (1). It is classified by the World Health Organisation as a variant of large-cell carcinoma. The presence of a few clear cells is not sufficient to make the diagnosis as they are said to occur in up to 10% of large-cell carcinomas that elsewhere show evidence of squamous or glandular differentiation (2). There are few reports of clear-cell carcinoma in the English literature (24), and it is the purpose of this study to describe two further cases, and particularly to stress some of the practical diagnostic problems. Case Reports CASE 1

The American Journal of Surgical Pathology, Mar 1, 2015

This study examines the presence of the EWSR1 rearrangement in a variety of clear cell salivary g... more This study examines the presence of the EWSR1 rearrangement in a variety of clear cell salivary gland carcinomas with myoepithelial differentiation. A total of 94 salivary gland carcinomas with a prominent clear cell component included 51 cases of clear cell myoepithelial carcinomas de novo (CCMC), 21 cases of CCMCs ex pleomorphic adenoma (CCMCexPA), 11 cases of epithelial-myoepithelial carcinoma (EMC), 6 cases of EMC with solid clear cell overgrowth, and 5 cases of hyalinizing clear cell carcinoma of minor salivary glands. In addition, 10 cases of myoepithelial carcinomas devoid of clear cell change and 12 cases of benign myoepithelioma were included as well. All the tumors in this spectrum were reviewed, reclassified, and tested by fluorescence in situ hybridization (FISH) for the EWSR1 rearrangement using the Probe Vysis EWSR1 Break Apart FISH Probe Kit. The EWSR1 rearrangement was detected in 20 of 51 (39%) cases of CCMC, in 5 of 21 (24%) cases of CCMCexPA, in 1 of 11 (9%) cases of EMC, and in 4 of 5 (80%) cases of hyalinizing clear cell carcinoma. The 25 EWSR1-rearranged CCMCs and CCMCexPAs shared similar histomorphology. They were arranged in nodules composed of compact nests of large polyhedral cells with abundant clear cytoplasm. Necrosis, areas of squamous metaplasia, and hyalinization were frequent features. Immunohistochemically, the tumors expressed p63 (96%), cytokeratin CK14 (96%), and S100 protein (88%). MIB1 index varied from 10% to 100%, with most cases in the 20% to 40% range. Clinical follow-up information was available in 21 cases (84%) and ranged from 3 months to 15 years (mean 5.2 y); 4 patients were lost to follow-up. Ten patients are alive with no evidence of recurrent or metastatic disease in the follow-up period from 3 months to 15 years (mean 5 y), 3 patients are alive with recurrent and metastatic disease, and 8 died of disseminated cancer 9 months to 16 years after diagnosis (mean 6 y). Lymph node metastasis appeared in 5 patients within 5 months to 4 years after diagnosis (mean 22 mo), distant metastases were noted in 7 patients with invasion of orbit (2 cases), and in 1 case each metastasis to the neck soft tissues, liver, lungs, mediastinum, and thoracic vertebra was noted. We describe for the first time EWSR1 gene rearrangement in a subset of myoepithelial carcinomas arising in minor and major salivary glands. The EWSR1-rearranged CCMC represents a distinctive aggressive variant composed predominantly of clear cells with frequent necrosis. Most EWSR1-rearranged CCMCs of salivary glands are characterized by poor clinical outcomes.

American Journal of Surgical Pathology, 2020

Background: Secretory carcinoma (SC), originally described as mammary analogue SC, is a predomina... more Background: Secretory carcinoma (SC), originally described as mammary analogue SC, is a predominantly low-grade salivary gland neoplasm characterized by a recurrent t(12;15)(p13;q25) translocation, resulting in ETV6-NTRK3 gene fusion. Recently, alternative ETV6-RET, ETV6-MAML3, and ETV6-MET fusions have been found in a subset of SCs lacking the classic ETV6-NTRK3 fusion transcript, but still harboring ETV6 gene rearrangements. Design: Forty-nine cases of SC revealing typical histomorphology and immunoprofile were analyzed by next-generation sequencing using the FusionPlex Solid Tumor kit (ArcherDX). All 49 cases of SC were also tested for ETV6, RET, and NTRK3 break by fluorescence in situ hybridization and for the common ETV6-NTRK3 fusions using reverse transcription polymerase chain reaction. Results: Of the 49 cases studied, 37 (76%) occurred in the parotid gland, 7 (14%) in the submandibular gland, 2 (4%) in the minor salivary glands, and 1 (2%) each in the nasal mucosa, facial s...

Journal of Medical Genetics, 1990

We report two male sibs and two female sibs from separate families, both with normal parents, who... more We report two male sibs and two female sibs from separate families, both with normal parents, who had a lethal condition with features of the Yunis-Varon syndrome and radiological signs of severe osteodysplasty. Autosomal recessive inheritance is likely in both families. The additional features described represent further delineation of the phenotype of the Yunis-Varon syndrome. The Yunis-Varon syndrome was recently reviewed by Hennekam and Vermeulen-Meiners' who added a further case to the seven reported previously. The condition was first described in 1980 when Yunis and Varon2 reported five patients from three Columbian families with cleidocranial dysostosis, severe micrognathia, bilateral absence of the thumbs and first metatarsal bones, and distal aphalangia. They all died before 10 weeks of age. The presence of consanguinity in three of the families reported and the lack of sex predilection were thought to be consistent with autosomal recessive inheritance. The four patients whom we describe had similar hands and feet and similar facial features to those described in the Yunis-Varon syndrome. However, our cases did not have absent clavicles and one pair of sibs reported here had pathological fractures. All four had generalised skeletal changes, including supraacetabular constrictions and flared metaphyses, not

Histopathology, 1999

AimsWe report a review of our institutional and consultation files in order to select cases of hi... more AimsWe report a review of our institutional and consultation files in order to select cases of hitherto unrecognized type of adenocarcinoma occurring in the tongue.Materials and resultsEight cases of a characteristic adenocarcinoma of the tongue resembled solid and follicular variants of the papillary carcinoma of the thyroid. All the tumours were unencapsulated and were divided by fibrous septa into lobules. Major parts of the lesions were composed of areas with solid and microcystic growth patterns. The most striking cytological feature was that the tumour nuclei were pale‐staining with a ‘ground glass’ quality, and they often appeared to overlap. Immunohistochemically, the tumours expressed cytokeratin and S100 protein and, focally, actin; thyroglobulin was negative. Ultrastructurally the cells had clefted nuclei, and the cytoplasm contained a few mitochondria, lysosomes and Golgi apparatus. Many tumour cells had combined features of both myoepithelial and secretory differentiati...

Advances in Anatomic Pathology, 2022

This review focuses on the heterogenous group of clear cell neoplasms of salivary glands and atte... more This review focuses on the heterogenous group of clear cell neoplasms of salivary glands and attempts to identify major differential diagnostic features. Within the head and neck region, clear cells are found most commonly in salivary gland tumors, but may also be seen in tumors of squamous or odontogenic epithelial origin, primary or metastatic carcinomas, benign or malignant melanocytic lesions, or benign or malignant mesenchymal tumors. Clear cells occur fairly commonly among a wide variety of salivary gland neoplasms, but mostly they constitute only a minor component of the tumor cell population. Clear cells represent a major diagnostic feature in two salivary gland neoplasms, epithelial-myoepithelial carcinoma and hyalinizing clear cell carcinoma. In addition, salivary gland neoplasms composed predominantly of clear cells could also include clear cell variants of other salivary neoplasms, such as mucoepidermoid carcinoma and myoepithelial carcinoma, but their tumor type-specific histologic features may only be available in limited nonclear cell areas of the tumor. Diagnosing predominantly clear cell salivary gland tumors is difficult because the immunoprofiles and morphologic features may overlap and the same tumor entity may also have a wide range of other histologic presentations. Many salivary gland tumors are characterized by tumor type-specific genomic alterations, particularly gene fusions of the ETV6 gene in secretory carcinoma, the MYB and MYBL1 genes in adenoid cystic carcinoma, the MAML2 gene in mucoepidermoid carcinoma, the EWSR1 gene in hyalinizing clear cell carcinoma, and others. Thus, along with conventional histopathologic examination and immunoprofiling, molecular and genetic tests may be important in the diagnosis of salivary gland clear cell tumors by demonstrating genetic alterations specific to them.