Variation in proliferative and cell cycle markers in Barrett's esophagus in relation to circumferential and axial location in the esophagus.

BACKGROUND: Adenocarcinoma in Barrett's esophagus (BE) occurs more frequently between 12 and 3 o'clock at the gastroesophageal junction (GEJ). METHODS: BE patients were prospectively recruited from December 2013 to July 2016. Expression of p53, Ki-67, cyclin-D1, COX-2 and p21 was assessed in quadrantic biopsies from the proximal and distal margins of the BE segments. Cell cycle marker association with current or subsequent dysplasia or adenocarcinoma was examined. RESULTS: 110 patients: median age 64 (IQR, 56-71) years; median BE segment length C4M6; and a median follow-up of 4.7 (IQR, 3.6-5.7) years. In total 13 (11.8%) had evidence of dysplasia or neoplasia (2.7% indefinite for dysplasia, 5.5% low grade, 1.8% high grade and 1.8% adenocarcinoma) at index endoscopy. Six (7%) developed dysplasia or neoplasia (1 low grade, 2 high grade and 3 adenocarcinoma) during follow-up. Ki-67 expression was highest at 3 o'clock, and overall was 49.6% higher in the 12-6 o'clock position compared to 6-12 o'clock [odds ratio (OR), 1.42 (95% confidence interval (CI), 1.00-2.12)]. A similar pattern was found with p21 [1.82 (1.00-3.47)]. There was increased expression of several markers in distal BE biopsies; cyclin-D1 [1.74 (1.29-2.34)]; Cyclo-oxygenase 2 [2.03 (1.48-2.78]) and p21 [2.06 (1.16-3.68)]. Expression of Ki-67 was lower in distal compared to proximal biopsies [0.58 (0.43-0.78)]. P53 expression had high specificity (93.8%) for subsequent low-grade dysplasia, high-grade dysplasia or adenocarcinoma. CONCLUSION: Increased cellular proliferation was seen at 12-6 o'clock at the GEJ. Cell-cycle marker expression was increased at the GEJ compared to the proximal BE segment. These findings mirror reflux esophagitis and suggest ongoing reflux contributes to the progression of dysplasia and malignancy in BE.

Malignant phyllodes tumour of the breast mimicking endometriosis.

A 63-year-old woman presented with a clinically malignant mass. Core biopsy showed features resembling endometriosis. The glands were GATA3 and oestrogen receptor positive consistent with mammary origin and had no myoepithelial layer. The excision also showed a fibroepithelial component with stromal overgrowth, frequent mitoses and invasive margin consistent with a malignant phyllodes tumour. KMT2D and SETD2 mutations were present in both the conventional phyllodes tumour and endometriosis-like areas and are also described in endometriosis raising interesting questions about these lesions. This unusual pattern is a potential diagnostic pitfall, so it is helpful to be aware of it.

Primary cutaneous osteosarcoma of the scalp in an immunosuppressed individual: A case report and review of the literature.

We report a case of a 76-year-old man presenting with a 12-month history of a solitary lesion on his scalp. The histopathology was consistent with a grade 2/3 osteosarcoma extending to the subcutis. Full-body imaging excluded any involvement of the underlying bony tissue or solid organ malignancy, thus a diagnosis of primary cutaneous osteosarcoma (PCO) was made. Given the exceedingly rare nature of PCO, we discuss the clinico-pathological features of this case and those previously reported in the literature.

Sphingosine-1-phosphate signalling drives an angiogenic transcriptional programme in diffuse large B cell lymphoma.

Although the over-expression of angiogenic factors is reported in diffuse large B-cell lymphoma (DLBCL), the poor response to anti-VEGF drugs observed in clinical trials suggests that angiogenesis in these tumours might be driven by VEGF-independent pathways. We show that sphingosine kinase-1 (SPHK1), which generates the potent bioactive sphingolipid sphingosine-1-phosphate (S1P), is over-expressed in DLBCL. A meta-analysis of over 2000 cases revealed that genes correlated with SPHK1 mRNA expression in DLBCL were significantly enriched for tumour angiogenesis meta-signature genes; an effect evident in both major cell of origin (COO) and stromal subtypes. Moreover, we found that S1P induces angiogenic signalling and a gene expression programme that is present within the tumour vasculature of SPHK1-expressing DLBCL. Importantly, S1PR1 functional antagonists, including Siponimod, and the S1P neutralising antibody, Sphingomab, inhibited S1P signalling in DLBCL cells in vitro. Furthermore, Siponimod, also reduced angiogenesis and tumour growth in an S1P-producing mouse model of angiogenic DLBCL. Our data define a potential role for S1P signalling in driving an angiogenic gene expression programme in the tumour vasculature of DLBCL and suggest novel opportunities to target S1P-mediated angiogenesis in patients with DLBCL.

Toxic epidermal necrolysis: the red eye and red herrings in casualty.

A 38-year-old woman presented to casualty with bilateral red eyes associated with a recent upper respiratory tract infection. This was initially diagnosed as conjunctivitis, however systemic review revealed an erythematous facial and skin rash, mildly swollen lips and mild swallowing difficulties. The patient was referred for an urgent medical assessment, by which time she was found to have erythema affecting 54% of her body surface area and diagnosed with suspected toxic epidermal necrolysis (TEN). She rapidly deteriorated over 24 hours with a spreading blistering skin rash and airway compromise requiring urgent intubation and admission to the intensive treatment unit (ITU). Subsequent skin biopsies confirmed the diagnosis of TEN, attributed to recent use of ibuprofen. Treatment included broad-spectrum antibiotics and high-dose corticosteroids. The patient had a prolonged hospital stay and developed severe scarring of the ocular surface. She was discharged home and remains under continuing outpatient follow-up with ophthalmology and dermatology teams.

Caesarean section scar causes myometrial hypertrophy with subsequent heavy menstrual flow and dysmenorrhoea.

In the recent years, maternity statistics world-wide show a continuous rise in the rate of Caesarean Section (CS) operation. Many CS deliveries are conducted despite having no clear obstetric indications. The CS scar is assumed to be related to many adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain; however, the mechanism of this relation is not clear. Further, little is known about the effects of CS scar on uterine wall morphology, function or patho-physiology. We hypothesize that: (i) the CS scar causes myometrial hypertrophy (myohypertrophy) of the anterior uterine wall above the scar, and (ii) the scar-induced morphological changes in the uterine wall causes adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain. This article discusses the hypothesis and its clinical implications, as well as presents supportive preliminary data and the emerging research to prove it.

A rare case of carbimazole-induced hepatitis in a patient with Graves' disease.

Although carbimazole-induced hepatitis is rare, clinicians should be aware of this potential complication and offer alternative treatment early.

Endometrial biopsy in women with abnormal uterine bleeding: inadequate and unassessable categorisation is not clinically relevant.

AIMS: Inadequate endometrial biopsy comprises a dilemma for gynaecologists and histopathologists alike. This study was conducted to assess the clinical merit of classifying scant endometrial biopsy into inadequate and unassessable using McCluggage criteria. METHODS: We retrospectively classified 268 endometrial biopsies, initially reported as inadequate, into inadequate (n=74) and unassessable (n=174) using McCluggage criteria after excluding 20 cases; all taken from patients aged ≥50 years with abnormal uterine bleeding attending Sandwell and West Birmingham Hospitals, UK from 1 January 2007 until 30 September 2012. The electronic clinical records were reviewed to find out the consequent clinical decisions and final outcomes. The follow-up period was 15 months after including the last patient. RESULTS: The median age was 57 years (range: 50-97), and the median number of visits to hospital till the diagnosis was achieved was 2 (range: 1-4). The final diagnosis of endometrial hyperplasia or cancer was reported in 9 cases; 5 (7.1%) with an initial finding of inadequate and 4 with unassessable (2.4%); the difference was statistically insignificant (p=0.13). More patients in the inadequate category (82.4%) underwent further investigations when compared with the unassessable category (68.4%); the difference was statistically significant (p=0.029). There was no statistically significant difference in the inadequate to unassessable ratio when the endometrial thickness was ≥5 mm or <5 mm within the Pipelle group (p=0.46) or the curettage group (p=0.34). CONCLUSIONS: Our findings suggest that categorising scant endometrial specimens into inadequate or unassessable has no clinical implications. The gynaecologist should interpret the histopathology report in the light of clinical scenario.

The effect of ethnicity on the presentation and management of oesophageal and gastric cancers: a UK perspective.

BACKGROUND: Studies show disparities in the management of oesophageal and gastric cancers between different ethnic groups. Asian patients with gastric adenocarcinoma present with less advanced disease and are more likely to undergo curative resection. For oesophageal cancer, the rate of surgery in Black patients is half that of Caucasians. However, these studies originate from the United States where demographics differ from that of the UK. METHODS: We undertook a 5-year retrospective audit of patients diagnosed with oesophageal and gastric cancers at City Hospital, Birmingham (UK), which serves three major ethnic groups: Caucasians, Blacks and Asians. RESULTS: Data were extracted from 244 patients' records that included 133 gastric and 111 oesophageal cancers. Caucasians were more likely to present within 3 months of symptom onset than Asians or Blacks. Asians were less likely to be referred for urgent endoscopy than Caucasians or Blacks (P<0.05). Significant differences in reported symptoms were found between ethnic groups with Caucasians more likely to report dysphagia and less likely to describe abdominal pain than other ethnic groups. There was a lower rate of curative operation for Asians but this did not reach significance. CONCLUSION: Ethnicity seems to influence health-seeking behaviour, with Caucasians more likely to present earlier for medical attention and Asian patients less likely to be referred for urgent endoscopy. Improvements in symptom education amongst patients and health professionals alike may accelerate referral and improve outcome. The favourable disease patterns reported in the United States 'Asians' and the lower surgery rates reported in the United States 'Blacks' are not shown in this UK population.

Philadelphia (Ph) chromosome-positive thrombocythemia without features of chronic myeloid leukemia in peripheral blood: natural history and diagnostic differentiation from Ph-negative essential thrombocythemia.

We have evaluated the clinical symptoms, hematological features, and natural history of 3 cases and 20 reported cases described as Philadelphia chromosome-positive (Ph+) essential thrombocythemia (ET). The presence of increased small mononuclear megakaryocytes in bone marrow smears and biopsy material in patients with pronounced thrombocytosis and no evidence of chronic myeloid leukemia (CML) in peripheral blood appeared to be a diagnostic clue to the diagnosis of Ph+ (essential) thrombocythemia. As compared to cases of reactive thrombocytosis, the megakaryocytes in Ph+ thrombocythemia are smaller than normal ones and typically have hypolobulated round nuclei. This contrasts with the finding of clustered mature and enlarged megakaryocytes in Ph-negative true ET. Patients diagnosed as Ph+ ET may progress to CML and show a high tendency to myelofibrosis and blastic transformation. These observations indicate that both Ph+ ET and Ph+ thrombocythemia associated with CML can be regarded as early manifestations of the chronic stable phase of CML.

Aplasia blanca pura con infiltrado linfoide T asociado a clomipramina. Presentación de un caso y revisión de la literatura / Pure white cell aplasia with marrow T cell infiltrate related to clomipramino case report and review of literature

Se presenta una paciente con aplasia blanca pura (abp) inducida por la droga antidepresiva clomipramina que cursa con agranulocitosis, fiebre y estomatitis candidiásica. La médula ósea mostraba ausencia de la serie granulocítica, eritropoyesis y trombopoyesis conservadas, e infiltración linfocitaria nodular T. La paciente evoluciona favorablemente con antibióticosantifúngicos y G-CSE. Siete años después la paciente está asintomática con leve neutropenia. Durante ese lapso varias biopsias de médula ósea mostraron persistencia de nódulos linfoideos pequeños con patrón de hiperplasia benigna. Se revisan los mecanismos patogénicos de la abp y su diagnóstico diferencial (AU)

Aplasia blanca pura con infiltrado linfoide T asociado a clomipramina. Presentación de un caso y revisión de la literatura / Pure white cell aplasia with marrow T cell infiltrate related to clomipramino case report and review of literature

Se presenta una paciente con aplasia blanca pura (abp) inducida por la droga antidepresiva clomipramina que cursa con agranulocitosis, fiebre y estomatitis candidiásica. La médula ósea mostraba ausencia de la serie granulocítica, eritropoyesis y trombopoyesis conservadas, e infiltración linfocitaria nodular T. La paciente evoluciona favorablemente con antibióticosantifúngicos y G-CSE. Siete años después la paciente está asintomática con leve neutropenia. Durante ese lapso varias biopsias de médula ósea mostraron persistencia de nódulos linfoideos pequeños con patrón de hiperplasia benigna. Se revisan los mecanismos patogénicos de la abp y su diagnóstico diferencial

Punción biopsia percutanea bajo control tomográfico y anatomopatológico: análisis retrospectivo de 86 casos / Percutaneous needle biopsy under tomographic and anatomo pathologic control: retrospective analysys of 86 cases

La biopsia pertutánea de lesiones superficiales o profundas bajo control tomográfico se ha desarrollado rápidamente en los últimos años. En este trabajo se analiza el rendimiento diagnóstico del método con asistencia del patólogo durante el acto de la biopsia. Se estudian retrospectivamente 86 casos. En 84 casos (97.6 por ciento) se obtuvo material apto para el diagnóstico. En tres casos (3.4 por ciento) se requirió la utilización de técnicas auxiliares (inmunohistoquímica) para alcanzar el diagnóstico definitivo de estirpe tumoral. La incidencia de complicaciones fue mínima (1.16 por ciento). Se concluye que el rendimiento del método es alto, con baja incidencia de complicaciones, evitando en muchos casos la realización de prácticas invasivas más complejas para llegar al diagnóstico de lesiones profundas (AU)

Punción biopsia percutanea bajo control tomográfico y anatomopatológico: análisis retrospectivo de 86 casos / Percutaneous needle biopsy under tomographic and anatomo pathologic control: retrospective analysys of 86 cases

La biopsia pertutánea de lesiones superficiales o profundas bajo control tomográfico se ha desarrollado rápidamente en los últimos años. En este trabajo se analiza el rendimiento diagnóstico del método con asistencia del patólogo durante el acto de la biopsia. Se estudian retrospectivamente 86 casos. En 84 casos (97.6 por ciento) se obtuvo material apto para el diagnóstico. En tres casos (3.4 por ciento) se requirió la utilización de técnicas auxiliares (inmunohistoquímica) para alcanzar el diagnóstico definitivo de estirpe tumoral. La incidencia de complicaciones fue mínima (1.16 por ciento). Se concluye que el rendimiento del método es alto, con baja incidencia de complicaciones, evitando en muchos casos la realización de prácticas invasivas más complejas para llegar al diagnóstico de lesiones profundas

Carcinoma lobulillar infiltrante de la mama : tipos histológicos y riesgo de metástasis en 126 casos / Infiltrating lobular carcinoma of the breast : histologic types and metastatic risk in 126 cases

A pesar del reconocimiento de diversas variantes histológicas, los factores pronóstico no están aún completamente definidos en el carcinoma lobulillar infiltrante (CLI) de la mama. Por otro lado, la prevalencia del CLI es muy variable en distintas series. Materiales y métodos : con el objeto de establecer la prevalencia del CLI y sus variantes, y de analizar los factores de riesgo de metástasis ganglionares (RMG), se estudiaron retrospectivamente todos los CLI en tres laboratorios de patología-Mar del Plata (MP), Bahía Blanca (BB) y tres Arroyos (TA)-entre el 1/8/92 y el 31/7/97. Se analizaron : edad, tamaño, bilateralidad, presencia de carcinoma lobulillar in situ (CLIS), tipo histológico, grado nuclear e índice micótico. Se investigó cuales de estas variables eran capaces de predecir el riesgo de metástasis ganglionares (RMG). Resultados : sobre un total de 1229 carcinomas mamarios infiltrantes, 736 correspondieron a MP, 408 a BB y 85 a TA. La incidencia general del CLI fue del 10 por ciento (n=126). La edad media fue de 59 años (35-87). Se halló CLIS en 49/ casos (38,8 por ciento). Seis casos (4,7 por ciento) mostraron bilateralidad (5 de ellos de la variante pleomórfica). 116 casos fueron grado nuclear 1 ó 2, y 20 casos grado nuclear 3. En 91 casos se extirparon ganglios axilares. El número de ganglios metastásicos osciló entre 1 y 18 (media 1,93; DS 4,42). En este grupo (n=91) se investigó la influencia de cada una de las variables en el RMG. La única variable estadísticamente significativa fue el tamaño tumoral (P<0,02). No se observaron diferencias significativas para desarrollar MG entre el tipo clásico y el resto de las variables consideradas en conjunto. Conclusión: la prevalencia de CLI en esta serie es del 10 por ciento y se halla en el centro del espectro de las ya publicadas. El tipo clásico representa el 60 por ciento, correspondiendo el 40 por ciento restante a las distintas variantes. El 15 por ciento de los casos corresponden a la variante pleomórfica. En los casos que aquí se analizan, la única variable significativa para predecir el riesgo de metástasis ganglionares fue el tamaño tumoral (AU)

Carcinoma lobulillar infiltrante de la mama : tipos histológicos y riesgo de metástasis en 126 casos / Infiltrating lobular carcinoma of the breast : histologic types and metastatic risk in 126 cases

A pesar del reconocimiento de diversas variantes histológicas, los factores pronóstico no están aún completamente definidos en el carcinoma lobulillar infiltrante (CLI) de la mama. Por otro lado, la prevalencia del CLI es muy variable en distintas series. Materiales y métodos : con el objeto de establecer la prevalencia del CLI y sus variantes, y de analizar los factores de riesgo de metástasis ganglionares (RMG), se estudiaron retrospectivamente todos los CLI en tres laboratorios de patología-Mar del Plata (MP), Bahía Blanca (BB) y tres Arroyos (TA)-entre el 1/8/92 y el 31/7/97. Se analizaron : edad, tamaño, bilateralidad, presencia de carcinoma lobulillar in situ (CLIS), tipo histológico, grado nuclear e índice micótico. Se investigó cuales de estas variables eran capaces de predecir el riesgo de metástasis ganglionares (RMG). Resultados : sobre un total de 1229 carcinomas mamarios infiltrantes, 736 correspondieron a MP, 408 a BB y 85 a TA. La incidencia general del CLI fue del 10 por ciento (n=126). La edad media fue de 59 años (35-87). Se halló CLIS en 49/ casos (38,8 por ciento). Seis casos (4,7 por ciento) mostraron bilateralidad (5 de ellos de la variante pleomórfica). 116 casos fueron grado nuclear 1 ó 2, y 20 casos grado nuclear 3. En 91 casos se extirparon ganglios axilares. El número de ganglios metastásicos osciló entre 1 y 18 (media 1,93; DS 4,42). En este grupo (n=91) se investigó la influencia de cada una de las variables en el RMG. La única variable estadísticamente significativa fue el tamaño tumoral (P<0,02). No se observaron diferencias significativas para desarrollar MG entre el tipo clásico y el resto de las variables consideradas en conjunto. Conclusión: la prevalencia de CLI en esta serie es del 10 por ciento y se halla en el centro del espectro de las ya publicadas. El tipo clásico representa el 60 por ciento, correspondiendo el 40 por ciento restante a las distintas variantes. El 15 por ciento de los casos corresponden a la variante pleomórfica. En los casos que aquí se analizan, la única variable significativa para predecir el riesgo de metástasis ganglionares fue el tamaño tumoral