Salvador J Diaz-Cano | King's College London (original) (raw)

Papers by Salvador J Diaz-Cano

Research paper thumbnail of Mo1128 THE SIGNIFICANCE OF HIGH GRADE DYSPLASIA ON BIOPSY SAMPLING PRIOR TO ENDOSCOPIC RESECTION OF LARGE COLORECTAL SUPERFICIAL NEOPLASTIC LESIONS AND HISTOPATHOLOGICAL FEATURES OF HIGH RISK LESIONS

Gastrointestinal Endoscopy, 2018

groups. Results: 424 patients received ESD, while 452 patients received STER. There was no signif... more groups. Results: 424 patients received ESD, while 452 patients received STER. There was no significant differences in age, gender, tumor size, depth and shape, en bloc resection rate, complications, postoperative hospital stay (p > 0.05). The patients receiving STER had apparently a longer procedure time due to closing the tunnel entrance (ESD vs STER, 23.2 AE 16.5 min vs 44.0 AE 25.8 min, p＜0.001). No recurrence and death was occurred in the STER and ESD groups during a mean follow-up of 50.0 and 51.8 months, respectively. Conclusions: Both ESD and STER would likely be effective and safe alternatives for resecting SMTs 10mm. Accounting for safety and preventing perforation, we are inclined to STER for SMTs > 10mm. Additionally, the choice between the two procedures will also depend on the depth and shape of submucosal tumors. Patients' clinical characteristics Characteristic ESD group STER group P value Number of patients 424 452 Mean age (SD), year 51.1 AE 10.5 50.3 AE 10.2 0.453 Gender, Female/Male 149/275 136/316 0.111 Location no. (%) 0.107 Upper 62 45 Middle 204 232 Lower 158 175 Macroscopic appearance no. (%) 0.188 regular 368 378 irregular 56 74 Tumor size, mean (SD), mm 1.2 AE 0.8 1.5 AE 0.7 0.078 Invasion depth no. (%) 0.883 Superficial MP 358 380 Deep MP 66 72 Pathology no. (%) 0.070 Leiomyoma 403 431 GIST 10 8 Granular cell tumors 8 2 Schwannoma 2 9 Clarifying fibrous tumors 1 2 Procedure time, min 23.2 AE 16.5 44.0 AE 25.8 ＜0.001 En bloc resection rate no. (%) 417 (98.3%) 446 (98.7%) 0.692 Complications no. (%) 0.436 Perforation 4 1 Pneumothorax/hydrothorax 8 6 Major bleeding 1 2 Postoperative hospital stay, day 2.4 AE 1.8 2.8 AE 1.9 0.099 Follow-up, month 51.8 AE 16.4 50.3 AE 15.1 0.112 Recurrence 0 0 1 Data are presented as number (no.

Research paper thumbnail of OWE-002 Significance of biopsies before large colorectal endoscopic resections and histopathological features of high risk lesions

Research paper thumbnail of Topographic expression of stem cell markers in differentiated thyroid follicular cell neoplasms

Histopathology

Background: Previous studies have looked at the expression of some stem cell markers in the thyro... more Background: Previous studies have looked at the expression of some stem cell markers in the thyroid, but no topographical analysis is available. We aim to assess topographically stem cell markers (CD44v6, OCT4, p63) in differentiated follicular cell thyroid proliferative lesions. Design: We selected 15 follicular thyroid hyperplastic nodules (FTHN), 11 follicular thyroid adenomas (FTA), seven minimally invasive follicular thyroid carcinomas (FTC-MI), 12 widely invasive follicular thyroid carcinomas (FTC-WI) and 13 papillary thyroid carcinomas (PTC) from the files of King’s College Hospital. All cases were formalin fixed paraffin embedded. Stem cell markers (CD44v6, OCT4, p63) were immunohistochemically detected in both periph- eral and internal compartments. Chi-squared, non-parametric ANOVA and stepwise discriminant analysis were performed by diagnostic group. Results were considered statistically significant if P < 0.05. Cross validation was done only for those cases in the ana...

Research paper thumbnail of Pseudofolliculitis barbae induced by oral minoxidil

Clinical and Experimental Dermatology, 2012

Figure 2 Chronic inflammatory infiltrate with evidence of ruptured abscess and fibrosis (haematox... more Figure 2 Chronic inflammatory infiltrate with evidence of ruptured abscess and fibrosis (haematoxylin and eosin, original magnification • 12.5).

Research paper thumbnail of Peripheral expression of stem cell markers for the prediction of morphological progression in differentiated thyroid follicular cell neoplasms

Histopathology

Background: No studies have looked at the expression of stem cell markers in thyroid neoplasms by... more Background: No studies have looked at the expression of stem cell markers in thyroid neoplasms by topographic compartments and growth patterns. Design: We analyzed combined primary and secondary growth pattern (one = tubulo-papillary, two = nested-trabecular, three = nodular-solid, four = diffuse), nuclear grade (high if more than two nuclear abnormalities, including chromatin, nucleolus, pleomor- phism and anisokaryosis) and confluent necrosis in 15 follicular thyroid hyperplastic nodules (FTHN), 11 follicular thyroid adeno- mas (FTA), seven minimally invasive follicular thyroid carcinomas (FTC-MI), 12 widely invasive follicular thyroid carcinomas (FTC- WI) and 13 papillary thyroid carcinomas (PTC) from the files of King’s College Hospital. All cases were formalin fixed paraffin embedded. Stem cell markers (CD44v6, OCT4, p63) were immuno- histochemically detected in both peripheral and internal compart- ments. Chi-square, non-parametric ANOVA (significant if P < 0.05) and stepwi...

Research paper thumbnail of Discriminating minor and major forms of drug reaction with eosinophilia and systemic symptoms: Facial edema aligns to the severe phenotype

Journal of The American Academy of Dermatology, Sep 1, 2021

BACKGROUND DRESS is a cutaneous and systemic drug allergy disorder. Patients exist on a severity ... more BACKGROUND DRESS is a cutaneous and systemic drug allergy disorder. Patients exist on a severity spectrum with some developing a mild form of the disorder which fails to meet the RegiSCAR diagnostic criteria for DRESS. OBJECTIVE We sought to determine if there were any cutaneous or dermatopathological features which discriminate between the mild form of DRESS ('DRESS minor') and the severe phenotype ('DRESS major'). METHODS Inpatients from a single centre with a diagnosis of DRESS were prospectively recruited over a 7-year period. Clinical and dermatopathological features were analysed to discriminate between DRESS minor and DRESS major. RESULTS 45 patients were included: 19 patients had a RegiSCAR score of ≤3 (DRESS minor), and 26 patients had a score ≥4 (DRESS major). The mean latency period (P=0.001), fever >38.5 oC (P=0.001), and a reaction lasting >15 days (P=0.010) discriminated DRESS major from DRESS minor. Facial oedema was the sole discerning cutaneous feature(P=0.025). Discriminating histopathological features included basal squamatisation (P=0.005), dermal red cell extravasation (P=0.009), and interface inflammation (P=0.005). CONCLUSION We propose a new classification system: DRESS minor, to distinguish the milder illness from the severe form, DRESS major. Facial oedema and certain histopathological features can help discriminate between major and minor versions.

Research paper thumbnail of PD-L1 Testing in Urothelial Carcinoma: Analysis of a Series of 1401 Cases Using Both the 22C3 and SP142 Assays

Pathology & Oncology Research, Apr 11, 2022

Immune checkpoint blockade (ICB) drugs are a novel, effective treatment for advanced urothelial c... more Immune checkpoint blockade (ICB) drugs are a novel, effective treatment for advanced urothelial carcinoma. Worldwide, several different ICB drugs are approved, each developed and clinically validated with a specific PD-L1 compound diagnostic assay. As a result, PD-L1 testing workflows in routine practice are complex: requiring multiple assays across two platforms, with each assay having a different method of interpretation. Our service tested 1,401 urothelial carcinoma cases for PD-L1 expression, using both the 22C3 PharmDx assay (required prior to Pembrolizumab therapy) and SP142 assay (required prior to Atezolizumab therapy). Of the 1,401 cases tested, 621 cases (44%) were tested with both the 22C3 PharmDx and SP142 assays, 492 cases (35%) with 22C3 PharmDx only, and 288 cases (21%) with SP142 only. Each assay was used and interpreted according to the manufacturer's guidelines. The rate of positivity we observed was 26% with the 22C3 assay and 31% with the SP142 assay, similar to the pre-licensing studies for both drugs. The discrepancy observed between the assays was 11%, which reinforces the requirement for utilisation of the correct assay for each agent, and limits potential cross-utility of assays. This aspect must be considered when setting up a PD-L1 testing strategy in laboratories where both Pembrolizumab and Atezolizumab are available for the treatment of urothelial carcinoma but also has broader implications for testing of other cancers where multiple ICB drugs and their respective assays are approved.

Research paper thumbnail of Coexistent intraurothelial carcinoma and muscle-invasive urothelial carcinoma of the bladder: clonality and somatic down-regulation of DNA mismatch repair

Human Pathology, Jul 1, 2009

Muscle-invasive urothelial carcinomas are heterogeneous neoplasms for which the clonal relationsh... more Muscle-invasive urothelial carcinomas are heterogeneous neoplasms for which the clonal relationship with low-grade urothelial dysplasia and carcinomas in situ remains unknown, and both monoclonal and field change models have been proposed. Low-grade dysplasia (18) and carcinoma in situ (12) associated with muscle-invasive urothelial carcinoma were microdissected and topographically analyzed (intraepithelial and invasive superficial and deep to muscularis mucosa) for methylation pattern of androgen receptor alleles, TP53, RB1, WT1, and NF1 microsatellite analysis to assess clonal identity; MLH1 and MSH2 sequencing/immunostaining. Appropriate controls were run. Carcinoma in situ (100%) and invasive urothelial carcinoma (100%) revealed monoclonal patterns, whereas low-grade dysplasia was preferentially polyclonal (80%). Carcinoma in situ showed aneuploid DNA content and more abnormal microsatellites than the corresponding invasive compartments, opposite to low-grade dysplasia. Absent MLH1 protein expression with no gene mutations were identified in carcinoma in situ and nodular-trabecular urothelial carcinoma with high microsatellite abnormalities. Somatic mismatch repair protein down-regulation and the accumulation of tumor suppressor gene microsatellite abnormalities contribute to a molecular evolution for monoclonal carcinoma in situ divergent from coexistent muscle-invasive urothelial carcinoma. Low-grade dysplasia is however unlikely connected with this molecular progression.

Research paper thumbnail of Immunotherapy with fingolimod improves outcome of experimental Graves’ disease and associated orbitopathy by modulating autoimmune response to thyroid stimulating hormone receptor

Investigative Ophthalmology & Visual Science, Jul 22, 2019

Research paper thumbnail of Coincidence of primary adrenocortical carcinoma and melanoma: three CASE reports

BMC Endocrine Disorders, Jan 6, 2023

Background Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a heterogeneous pro... more Background Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a heterogeneous prognosis, while adrenal metastasis from other primary cancers, including melanoma, may occur more frequently. ACC may rarely occur as part of familial cancer syndromes, but even in sporadic cases, a significant proportion of patients had other malignancies before or after diagnosis of ACC. Herein we present three cases where sporadic ACC was identified in patients with coexistent or previous history of melanoma. Case description Patient 1-A 37-yr-old man with a superficial spreading BRAF-positive melanoma was found to harbour a progressively growing left adrenal mass. Initially, he was suspected of having adrenal metastasis, but the histology after adrenalectomy confirmed ACC. Patient 2-A 68-year-old man with a history of recurrent BRAF-positive melanoma was diagnosed with disseminated metastatic melanoma recurrence, including a rapidly enlarging left adrenal mass. Consequently, he underwent left adrenalectomy, and histology again confirmed ACC. Patient 3-A 50-yr-old man was referred with histological diagnosis of metastatic ACC. He had a background history of pT1 melanoma. We undertook targeted sequencing of ACC tissue samples in all cases. Somatic variants were observed in the known driver genes CTNNB1 (Patient 1), APC and KMT2D (Patient 2), and APC and TP53 (Patient 3). Germline TP53 variants (Li-Fraumeni syndrome) were excluded in all cases. Retrospective review of our patient cohort in the last 21 years revealed a frequency of 0.5% of histologically diagnosed melanoma metastasis among patients referred for adrenal masses. On the other hand, 1.6% of patients with histologically confirmed ACC had a previous history of melanoma. Conclusion Sporadic ACC can occur in the background of melanoma, even if adrenal metastasis might appear to be the most likely diagnosis. Coexistent primary adrenal malignancy should be considered and investigated for in all patients with a history of melanoma with suspicious adrenal lesions.

Research paper thumbnail of Ocular neuroendocrine tumour metastases - presentation & outcome

Endocrine Abstracts, Nov 22, 2022

Research paper thumbnail of Szlaki molekularne w raku kory nadnercza — od wiedzy o sygnalizacji komórkowej do metod diagnostyki i leczenia

Endokrynologia Polska, Oct 29, 2015

Adrenocortical carcinoma is associated with a low cure rate and a high recurrence rate. The progn... more Adrenocortical carcinoma is associated with a low cure rate and a high recurrence rate. The prognosis is poor, and at diagnosis 30-40% of cases are already metastatic. The current therapeutic options (surgical resection, followed by adjuvant mitotane treatment +/chemotherapy) are limited, and the results remain unsatisfactory. Key molecular events that contribute to formation of adrenocortical cancer are IGF2 overexpression, TP53-inactivating mutations, and constitutive activation of the Wnt/b-catenin signalling pathway via activating mutations of the b-catenin gene. The underlying genetic causes of inherited tumour syndromes have provided insights into molecular pathogenesis. The increased occurrence of adrenocortical tumours in Li-Fraumeni and Beckwith-Wiedemann syndromes, and Carney complex, has highlighted the roles of specific susceptibility genes: TP53, IGF2, and PRKAR1A, respectively. Further studies have confirmed that these genes are also involved in sporadic tumour cases. Crucially, transcriptome-wide studies have determined the differences between malignant and benign adrenocortical tumours, providing potential diagnostic tools. In conclusion, enhancing our understanding of the molecular events of adrenocortical tumourigenesis, especially with regard to the signalling pathways that may be disrupted, will greatly contribute to improving a range of available diagnostic, prognostic, and treatment approaches.

Research paper thumbnail of Influence of intratumour heterogeneity in the interpretation of marker results in phaeochromocytomas

The Journal of Pathology, Dec 1, 1999

Research paper thumbnail of Ectopic hyperprolactinaemia due to a malignant uterine tumor resembling ovarian sex cord tumors (UTROCST)

Pituitary, Aug 28, 2020

Purpose Moderate hyperprolactinaemia (2-5 times upper limit of normal) occurring in a patient wit... more Purpose Moderate hyperprolactinaemia (2-5 times upper limit of normal) occurring in a patient with a normal pituitary MRI is generally considered to be due to a lesion below the level of detection of the MRI scanner assuming macroprolactin and stress have been excluded. Most patients with mild-to-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We present the rare case of a patient who had prolactin elevation typical of a prolactin-secreting pituitary macroadenoma,with a normal cranial MRI, and in whom the prolactin rose further with dopamine agonist treatment. Subsequent investigations revealed ectopic hyperprolactinaemia to a uterine tumor resembling ovarian sex cord tumor (UTROSCT) which resolved following tumor resection. Although mostly considered to be benign, the UTROSCT recurred with recurrent hyperprolactinaemia and intraabdominal metastases. Methods We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically. Results Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT. Conclusions Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10× ULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs.

Research paper thumbnail of Eruptive Lichen Planus Triggered by Acupuncture

Archives of Dermatology, Mar 1, 2011

Research paper thumbnail of No activating point mutation in Cyclin-Dependent Kinase 4 (CDK4) in pituitary adenomas, insulinomas and Leydig cell tumours

193rd Meeting of the Society for Endocrinology and Society for Endocrinology joint Endocrinology and Diabetes Day, Nov 1, 2002

Research paper thumbnail of Microsatellite instability testing in colorectal patients with Lynch syndrome: lessons learned from a case report and how to avoid such pitfalls

Personalized Medicine, Jul 1, 2022

We present the case of a patient with Lynch syndrome and metastatic colorectal carcinoma (mCRC). ... more We present the case of a patient with Lynch syndrome and metastatic colorectal carcinoma (mCRC). The initial immunohistochemistry (IHC) test for deficient mismatch repair gave a false negative result. However, the same mutation has accurately has been detected with IHC in other cancers with microsatellite instability (MSI) This supports the determining role of somatic missense mutations in MMR IHC. MSI-PCR testing confirmed MSI and the patient benefited from nivolumab with a complete metabolic response. We explain the rationale for immunotherapy in mCRC, current testing strategies and discuss future developments in MSI testing. We advocate for upfront testing using both IHC and MSI-PCR to direct therapy in mCRC, and a greater understanding of IHC and MSI-PCR testing pitfalls. Plain language summary: Bowel cancer that has spread is a serious condition that will often lead to loss of life. There is a new treatment called immunotherapy which helps extend the life of people with cancer that has spread beyond the bowel, but it does not work for everyone. Immunotherapy works best for people whose tumors have lost the ability to repair DNA. People with Lynch syndrome often have these types of tumors because they are born with an inherited predisposition for faulty DNA repair. We treated a patient with Lynch syndrome and bowel cancer, and wanted to use immunotherapy, but the test we used failed to give the right result. We think this is because the test is not very good at picking up unusual types of mutations that can occur and that using another test as well will prevent this mistake from happening to others.

Research paper thumbnail of Changes in Colonic Structure and Mucosal Inflammation

Research paper thumbnail of Hyperprolactinaemia resistant to dopamine agonist due to an ectopic source of prolactin arising from a Uterine Tumour Resembling Ovarian Sex Cord Tumours (UTROCST)

Endocrine Abstracts, Apr 9, 2018

Introduction: Moderate hyperprolactinaemia occurring in a patient with a normal pituitary MRI, as... more Introduction: Moderate hyperprolactinaemia occurring in a patient with a normal pituitary MRI, assuming macroprolactin and stress are excluded, is generally considered to be due to a lesion below the level of detection of the MRI scanner. Most patients with mild-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We describe a patient who had prolactin elevation typical of a prolactin-secreting macroadenoma, but with a normal MRI, and in whom the prolactin rose further with dopamine agonist treatment. Case: A 46 year-old female presented with 12 months history of secondary amenorrhoea without galactorrhoea. Prolactin was 4746 mIU/l without macroprolactin complexes, LH & FSH were low and oestradiol was undetectable. She had normal visual fields and no other clinical or biochemical features of

Research paper thumbnail of An unusual cause for a psoriasiform dermatosis

Clinical and Experimental Dermatology, Dec 9, 2016

A 79-year-old woman presented with a 5-month history of a painful dermatosis affecting her hands ... more A 79-year-old woman presented with a 5-month history of a painful dermatosis affecting her hands and feet. This developed into inflammation with fissuring, affecting the fingers and toes. The patient was a current smoker with a 65-pack-year history. She had no other medical conditions, no respiratory symptoms and was otherwise systemically well.

Research paper thumbnail of Mo1128 THE SIGNIFICANCE OF HIGH GRADE DYSPLASIA ON BIOPSY SAMPLING PRIOR TO ENDOSCOPIC RESECTION OF LARGE COLORECTAL SUPERFICIAL NEOPLASTIC LESIONS AND HISTOPATHOLOGICAL FEATURES OF HIGH RISK LESIONS

Gastrointestinal Endoscopy, 2018

groups. Results: 424 patients received ESD, while 452 patients received STER. There was no signif... more groups. Results: 424 patients received ESD, while 452 patients received STER. There was no significant differences in age, gender, tumor size, depth and shape, en bloc resection rate, complications, postoperative hospital stay (p > 0.05). The patients receiving STER had apparently a longer procedure time due to closing the tunnel entrance (ESD vs STER, 23.2 AE 16.5 min vs 44.0 AE 25.8 min, p＜0.001). No recurrence and death was occurred in the STER and ESD groups during a mean follow-up of 50.0 and 51.8 months, respectively. Conclusions: Both ESD and STER would likely be effective and safe alternatives for resecting SMTs 10mm. Accounting for safety and preventing perforation, we are inclined to STER for SMTs > 10mm. Additionally, the choice between the two procedures will also depend on the depth and shape of submucosal tumors. Patients' clinical characteristics Characteristic ESD group STER group P value Number of patients 424 452 Mean age (SD), year 51.1 AE 10.5 50.3 AE 10.2 0.453 Gender, Female/Male 149/275 136/316 0.111 Location no. (%) 0.107 Upper 62 45 Middle 204 232 Lower 158 175 Macroscopic appearance no. (%) 0.188 regular 368 378 irregular 56 74 Tumor size, mean (SD), mm 1.2 AE 0.8 1.5 AE 0.7 0.078 Invasion depth no. (%) 0.883 Superficial MP 358 380 Deep MP 66 72 Pathology no. (%) 0.070 Leiomyoma 403 431 GIST 10 8 Granular cell tumors 8 2 Schwannoma 2 9 Clarifying fibrous tumors 1 2 Procedure time, min 23.2 AE 16.5 44.0 AE 25.8 ＜0.001 En bloc resection rate no. (%) 417 (98.3%) 446 (98.7%) 0.692 Complications no. (%) 0.436 Perforation 4 1 Pneumothorax/hydrothorax 8 6 Major bleeding 1 2 Postoperative hospital stay, day 2.4 AE 1.8 2.8 AE 1.9 0.099 Follow-up, month 51.8 AE 16.4 50.3 AE 15.1 0.112 Recurrence 0 0 1 Data are presented as number (no.

Research paper thumbnail of OWE-002 Significance of biopsies before large colorectal endoscopic resections and histopathological features of high risk lesions

Research paper thumbnail of Topographic expression of stem cell markers in differentiated thyroid follicular cell neoplasms

Histopathology

Background: Previous studies have looked at the expression of some stem cell markers in the thyro... more Background: Previous studies have looked at the expression of some stem cell markers in the thyroid, but no topographical analysis is available. We aim to assess topographically stem cell markers (CD44v6, OCT4, p63) in differentiated follicular cell thyroid proliferative lesions. Design: We selected 15 follicular thyroid hyperplastic nodules (FTHN), 11 follicular thyroid adenomas (FTA), seven minimally invasive follicular thyroid carcinomas (FTC-MI), 12 widely invasive follicular thyroid carcinomas (FTC-WI) and 13 papillary thyroid carcinomas (PTC) from the files of King’s College Hospital. All cases were formalin fixed paraffin embedded. Stem cell markers (CD44v6, OCT4, p63) were immunohistochemically detected in both periph- eral and internal compartments. Chi-squared, non-parametric ANOVA and stepwise discriminant analysis were performed by diagnostic group. Results were considered statistically significant if P < 0.05. Cross validation was done only for those cases in the ana...

Research paper thumbnail of Pseudofolliculitis barbae induced by oral minoxidil

Clinical and Experimental Dermatology, 2012

Figure 2 Chronic inflammatory infiltrate with evidence of ruptured abscess and fibrosis (haematox... more Figure 2 Chronic inflammatory infiltrate with evidence of ruptured abscess and fibrosis (haematoxylin and eosin, original magnification • 12.5).

Research paper thumbnail of Peripheral expression of stem cell markers for the prediction of morphological progression in differentiated thyroid follicular cell neoplasms

Histopathology

Background: No studies have looked at the expression of stem cell markers in thyroid neoplasms by... more Background: No studies have looked at the expression of stem cell markers in thyroid neoplasms by topographic compartments and growth patterns. Design: We analyzed combined primary and secondary growth pattern (one = tubulo-papillary, two = nested-trabecular, three = nodular-solid, four = diffuse), nuclear grade (high if more than two nuclear abnormalities, including chromatin, nucleolus, pleomor- phism and anisokaryosis) and confluent necrosis in 15 follicular thyroid hyperplastic nodules (FTHN), 11 follicular thyroid adeno- mas (FTA), seven minimally invasive follicular thyroid carcinomas (FTC-MI), 12 widely invasive follicular thyroid carcinomas (FTC- WI) and 13 papillary thyroid carcinomas (PTC) from the files of King’s College Hospital. All cases were formalin fixed paraffin embedded. Stem cell markers (CD44v6, OCT4, p63) were immuno- histochemically detected in both peripheral and internal compart- ments. Chi-square, non-parametric ANOVA (significant if P < 0.05) and stepwi...

Research paper thumbnail of Discriminating minor and major forms of drug reaction with eosinophilia and systemic symptoms: Facial edema aligns to the severe phenotype

Journal of The American Academy of Dermatology, Sep 1, 2021

BACKGROUND DRESS is a cutaneous and systemic drug allergy disorder. Patients exist on a severity ... more BACKGROUND DRESS is a cutaneous and systemic drug allergy disorder. Patients exist on a severity spectrum with some developing a mild form of the disorder which fails to meet the RegiSCAR diagnostic criteria for DRESS. OBJECTIVE We sought to determine if there were any cutaneous or dermatopathological features which discriminate between the mild form of DRESS ('DRESS minor') and the severe phenotype ('DRESS major'). METHODS Inpatients from a single centre with a diagnosis of DRESS were prospectively recruited over a 7-year period. Clinical and dermatopathological features were analysed to discriminate between DRESS minor and DRESS major. RESULTS 45 patients were included: 19 patients had a RegiSCAR score of ≤3 (DRESS minor), and 26 patients had a score ≥4 (DRESS major). The mean latency period (P=0.001), fever >38.5 oC (P=0.001), and a reaction lasting >15 days (P=0.010) discriminated DRESS major from DRESS minor. Facial oedema was the sole discerning cutaneous feature(P=0.025). Discriminating histopathological features included basal squamatisation (P=0.005), dermal red cell extravasation (P=0.009), and interface inflammation (P=0.005). CONCLUSION We propose a new classification system: DRESS minor, to distinguish the milder illness from the severe form, DRESS major. Facial oedema and certain histopathological features can help discriminate between major and minor versions.

Research paper thumbnail of PD-L1 Testing in Urothelial Carcinoma: Analysis of a Series of 1401 Cases Using Both the 22C3 and SP142 Assays

Pathology & Oncology Research, Apr 11, 2022

Immune checkpoint blockade (ICB) drugs are a novel, effective treatment for advanced urothelial c... more Immune checkpoint blockade (ICB) drugs are a novel, effective treatment for advanced urothelial carcinoma. Worldwide, several different ICB drugs are approved, each developed and clinically validated with a specific PD-L1 compound diagnostic assay. As a result, PD-L1 testing workflows in routine practice are complex: requiring multiple assays across two platforms, with each assay having a different method of interpretation. Our service tested 1,401 urothelial carcinoma cases for PD-L1 expression, using both the 22C3 PharmDx assay (required prior to Pembrolizumab therapy) and SP142 assay (required prior to Atezolizumab therapy). Of the 1,401 cases tested, 621 cases (44%) were tested with both the 22C3 PharmDx and SP142 assays, 492 cases (35%) with 22C3 PharmDx only, and 288 cases (21%) with SP142 only. Each assay was used and interpreted according to the manufacturer's guidelines. The rate of positivity we observed was 26% with the 22C3 assay and 31% with the SP142 assay, similar to the pre-licensing studies for both drugs. The discrepancy observed between the assays was 11%, which reinforces the requirement for utilisation of the correct assay for each agent, and limits potential cross-utility of assays. This aspect must be considered when setting up a PD-L1 testing strategy in laboratories where both Pembrolizumab and Atezolizumab are available for the treatment of urothelial carcinoma but also has broader implications for testing of other cancers where multiple ICB drugs and their respective assays are approved.

Research paper thumbnail of Coexistent intraurothelial carcinoma and muscle-invasive urothelial carcinoma of the bladder: clonality and somatic down-regulation of DNA mismatch repair

Human Pathology, Jul 1, 2009

Muscle-invasive urothelial carcinomas are heterogeneous neoplasms for which the clonal relationsh... more Muscle-invasive urothelial carcinomas are heterogeneous neoplasms for which the clonal relationship with low-grade urothelial dysplasia and carcinomas in situ remains unknown, and both monoclonal and field change models have been proposed. Low-grade dysplasia (18) and carcinoma in situ (12) associated with muscle-invasive urothelial carcinoma were microdissected and topographically analyzed (intraepithelial and invasive superficial and deep to muscularis mucosa) for methylation pattern of androgen receptor alleles, TP53, RB1, WT1, and NF1 microsatellite analysis to assess clonal identity; MLH1 and MSH2 sequencing/immunostaining. Appropriate controls were run. Carcinoma in situ (100%) and invasive urothelial carcinoma (100%) revealed monoclonal patterns, whereas low-grade dysplasia was preferentially polyclonal (80%). Carcinoma in situ showed aneuploid DNA content and more abnormal microsatellites than the corresponding invasive compartments, opposite to low-grade dysplasia. Absent MLH1 protein expression with no gene mutations were identified in carcinoma in situ and nodular-trabecular urothelial carcinoma with high microsatellite abnormalities. Somatic mismatch repair protein down-regulation and the accumulation of tumor suppressor gene microsatellite abnormalities contribute to a molecular evolution for monoclonal carcinoma in situ divergent from coexistent muscle-invasive urothelial carcinoma. Low-grade dysplasia is however unlikely connected with this molecular progression.

Research paper thumbnail of Immunotherapy with fingolimod improves outcome of experimental Graves’ disease and associated orbitopathy by modulating autoimmune response to thyroid stimulating hormone receptor

Investigative Ophthalmology & Visual Science, Jul 22, 2019

Research paper thumbnail of Coincidence of primary adrenocortical carcinoma and melanoma: three CASE reports

BMC Endocrine Disorders, Jan 6, 2023

Background Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a heterogeneous pro... more Background Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a heterogeneous prognosis, while adrenal metastasis from other primary cancers, including melanoma, may occur more frequently. ACC may rarely occur as part of familial cancer syndromes, but even in sporadic cases, a significant proportion of patients had other malignancies before or after diagnosis of ACC. Herein we present three cases where sporadic ACC was identified in patients with coexistent or previous history of melanoma. Case description Patient 1-A 37-yr-old man with a superficial spreading BRAF-positive melanoma was found to harbour a progressively growing left adrenal mass. Initially, he was suspected of having adrenal metastasis, but the histology after adrenalectomy confirmed ACC. Patient 2-A 68-year-old man with a history of recurrent BRAF-positive melanoma was diagnosed with disseminated metastatic melanoma recurrence, including a rapidly enlarging left adrenal mass. Consequently, he underwent left adrenalectomy, and histology again confirmed ACC. Patient 3-A 50-yr-old man was referred with histological diagnosis of metastatic ACC. He had a background history of pT1 melanoma. We undertook targeted sequencing of ACC tissue samples in all cases. Somatic variants were observed in the known driver genes CTNNB1 (Patient 1), APC and KMT2D (Patient 2), and APC and TP53 (Patient 3). Germline TP53 variants (Li-Fraumeni syndrome) were excluded in all cases. Retrospective review of our patient cohort in the last 21 years revealed a frequency of 0.5% of histologically diagnosed melanoma metastasis among patients referred for adrenal masses. On the other hand, 1.6% of patients with histologically confirmed ACC had a previous history of melanoma. Conclusion Sporadic ACC can occur in the background of melanoma, even if adrenal metastasis might appear to be the most likely diagnosis. Coexistent primary adrenal malignancy should be considered and investigated for in all patients with a history of melanoma with suspicious adrenal lesions.

Research paper thumbnail of Ocular neuroendocrine tumour metastases - presentation & outcome

Endocrine Abstracts, Nov 22, 2022

Research paper thumbnail of Szlaki molekularne w raku kory nadnercza — od wiedzy o sygnalizacji komórkowej do metod diagnostyki i leczenia

Endokrynologia Polska, Oct 29, 2015

Adrenocortical carcinoma is associated with a low cure rate and a high recurrence rate. The progn... more Adrenocortical carcinoma is associated with a low cure rate and a high recurrence rate. The prognosis is poor, and at diagnosis 30-40% of cases are already metastatic. The current therapeutic options (surgical resection, followed by adjuvant mitotane treatment +/chemotherapy) are limited, and the results remain unsatisfactory. Key molecular events that contribute to formation of adrenocortical cancer are IGF2 overexpression, TP53-inactivating mutations, and constitutive activation of the Wnt/b-catenin signalling pathway via activating mutations of the b-catenin gene. The underlying genetic causes of inherited tumour syndromes have provided insights into molecular pathogenesis. The increased occurrence of adrenocortical tumours in Li-Fraumeni and Beckwith-Wiedemann syndromes, and Carney complex, has highlighted the roles of specific susceptibility genes: TP53, IGF2, and PRKAR1A, respectively. Further studies have confirmed that these genes are also involved in sporadic tumour cases. Crucially, transcriptome-wide studies have determined the differences between malignant and benign adrenocortical tumours, providing potential diagnostic tools. In conclusion, enhancing our understanding of the molecular events of adrenocortical tumourigenesis, especially with regard to the signalling pathways that may be disrupted, will greatly contribute to improving a range of available diagnostic, prognostic, and treatment approaches.

Research paper thumbnail of Influence of intratumour heterogeneity in the interpretation of marker results in phaeochromocytomas

The Journal of Pathology, Dec 1, 1999

Research paper thumbnail of Ectopic hyperprolactinaemia due to a malignant uterine tumor resembling ovarian sex cord tumors (UTROCST)

Pituitary, Aug 28, 2020

Purpose Moderate hyperprolactinaemia (2-5 times upper limit of normal) occurring in a patient wit... more Purpose Moderate hyperprolactinaemia (2-5 times upper limit of normal) occurring in a patient with a normal pituitary MRI is generally considered to be due to a lesion below the level of detection of the MRI scanner assuming macroprolactin and stress have been excluded. Most patients with mild-to-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We present the rare case of a patient who had prolactin elevation typical of a prolactin-secreting pituitary macroadenoma,with a normal cranial MRI, and in whom the prolactin rose further with dopamine agonist treatment. Subsequent investigations revealed ectopic hyperprolactinaemia to a uterine tumor resembling ovarian sex cord tumor (UTROSCT) which resolved following tumor resection. Although mostly considered to be benign, the UTROSCT recurred with recurrent hyperprolactinaemia and intraabdominal metastases. Methods We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically. Results Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT. Conclusions Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10× ULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs.

Research paper thumbnail of Eruptive Lichen Planus Triggered by Acupuncture

Archives of Dermatology, Mar 1, 2011

Research paper thumbnail of No activating point mutation in Cyclin-Dependent Kinase 4 (CDK4) in pituitary adenomas, insulinomas and Leydig cell tumours

193rd Meeting of the Society for Endocrinology and Society for Endocrinology joint Endocrinology and Diabetes Day, Nov 1, 2002

Research paper thumbnail of Microsatellite instability testing in colorectal patients with Lynch syndrome: lessons learned from a case report and how to avoid such pitfalls

Personalized Medicine, Jul 1, 2022

We present the case of a patient with Lynch syndrome and metastatic colorectal carcinoma (mCRC). ... more We present the case of a patient with Lynch syndrome and metastatic colorectal carcinoma (mCRC). The initial immunohistochemistry (IHC) test for deficient mismatch repair gave a false negative result. However, the same mutation has accurately has been detected with IHC in other cancers with microsatellite instability (MSI) This supports the determining role of somatic missense mutations in MMR IHC. MSI-PCR testing confirmed MSI and the patient benefited from nivolumab with a complete metabolic response. We explain the rationale for immunotherapy in mCRC, current testing strategies and discuss future developments in MSI testing. We advocate for upfront testing using both IHC and MSI-PCR to direct therapy in mCRC, and a greater understanding of IHC and MSI-PCR testing pitfalls. Plain language summary: Bowel cancer that has spread is a serious condition that will often lead to loss of life. There is a new treatment called immunotherapy which helps extend the life of people with cancer that has spread beyond the bowel, but it does not work for everyone. Immunotherapy works best for people whose tumors have lost the ability to repair DNA. People with Lynch syndrome often have these types of tumors because they are born with an inherited predisposition for faulty DNA repair. We treated a patient with Lynch syndrome and bowel cancer, and wanted to use immunotherapy, but the test we used failed to give the right result. We think this is because the test is not very good at picking up unusual types of mutations that can occur and that using another test as well will prevent this mistake from happening to others.

Research paper thumbnail of Changes in Colonic Structure and Mucosal Inflammation

Research paper thumbnail of Hyperprolactinaemia resistant to dopamine agonist due to an ectopic source of prolactin arising from a Uterine Tumour Resembling Ovarian Sex Cord Tumours (UTROCST)

Endocrine Abstracts, Apr 9, 2018

Introduction: Moderate hyperprolactinaemia occurring in a patient with a normal pituitary MRI, as... more Introduction: Moderate hyperprolactinaemia occurring in a patient with a normal pituitary MRI, assuming macroprolactin and stress are excluded, is generally considered to be due to a lesion below the level of detection of the MRI scanner. Most patients with mild-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We describe a patient who had prolactin elevation typical of a prolactin-secreting macroadenoma, but with a normal MRI, and in whom the prolactin rose further with dopamine agonist treatment. Case: A 46 year-old female presented with 12 months history of secondary amenorrhoea without galactorrhoea. Prolactin was 4746 mIU/l without macroprolactin complexes, LH & FSH were low and oestradiol was undetectable. She had normal visual fields and no other clinical or biochemical features of

Research paper thumbnail of An unusual cause for a psoriasiform dermatosis

Clinical and Experimental Dermatology, Dec 9, 2016

A 79-year-old woman presented with a 5-month history of a painful dermatosis affecting her hands ... more A 79-year-old woman presented with a 5-month history of a painful dermatosis affecting her hands and feet. This developed into inflammation with fissuring, affecting the fingers and toes. The patient was a current smoker with a 65-pack-year history. She had no other medical conditions, no respiratory symptoms and was otherwise systemically well.