RESUMEN
Fibroadenomas are benign breast tumors with a rare incidence of malignant transformation. Carcinoma arising within fibroadenomas typically occurs in women above the age of 40. We present a case of a young patient with microinvasive carcinoma arising within a biopsy-proven fibroadenoma, highlighting the possibility of carcinoma arising within fibroadenomas in young patients and the importance of vigilant surveillance even after a benign biopsy. In younger patients, new suspicious changes in benign lesions should be investigated. If prior core needle biopsy was performed, excision biopsy should be considered as the malignancy may be small and may be missed on needle biopsy.
RESUMEN
Inflammatory myofibroblastic tumor (IMT) is a myofibroblastic/fibroblastic neoplasm of intermediate malignant potential. It is frequently characterized by genetic fusion of ALK with a variety of partner genes, which results in the activated ALK signaling pathway that can be targeted with kinase inhibitors. IMTs can occur in the gynecologic tract, with the uterus (corpus and cervix) being the most frequent site. Recent studies suggest that IMTs in the gynecologic tract are underrecognized, and a low-threshold for performing ALK immunohistochemistry has been proposed. The aim of this study was to evaluate the specificity of ALK immunohistochemistry for IMTs among uterine mesenchymal and mixed epithelial/mesenchymal tumors. We performed ALK immunohistochemistry on 14 molecularly confirmed uterine IMTs and 260 other uterine pure mesenchymal and mixed epithelial/mesenchymal tumors. Cases showing any positive cytoplasmic and/or membranous staining of the tumor cells were considered to be ALK positive. All 14 IMTs were confirmed to harbor ALK genetic fusion by RNA sequencing, and ALK immunostaining in the form of granular cytoplasmic positivity with paranuclear accentuation was observed in all 14 cases. ALK was negative (complete absence of staining) in all the other pure mesenchymal tumors and in all mixed epithelial/mesenchymal tumors examined. Our findings show that ALK is a highly specific diagnostic immunohistochemical marker for ALK fusion in uterine mesenchymal tumors. In the work-up of uterine mesenchymal tumors, particularly smooth muscle tumors showing myxoid stromal changes, a diagnosis of IMT should be strongly considered if ALK positivity is observed.
Asunto(s)
Quinasa de Linfoma Anaplásico/análisis , Biomarcadores de Tumor/análisis , Inmunohistoquímica , Neoplasias de los Tejidos Conjuntivo y Blando/enzimología , Neoplasias Uterinas/enzimología , Adulto , Anciano , Quinasa de Linfoma Anaplásico/genética , Biomarcadores de Tumor/genética , Femenino , Fusión Génica , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Neoplasias de los Tejidos Conjuntivo y Blando/genética , Neoplasias de los Tejidos Conjuntivo y Blando/patología , Fenotipo , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Análisis de Secuencia de ARN , Análisis de Matrices Tisulares , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologíaRESUMEN
INTRODUCTION: Adenoid cystic carcinomas (ACC) of the breast are extremely rare tumours, accounting for <0.1% of newly diagnosed breast cancer cases. Little data exist regarding the correlation of radiological findings with histology of this rare subtype. To our knowledge, gross size discrepancy between the 2 modalities has not been reported. We describe a case of ACC with appreciable size discordance between imaging and pathology report. PRESENTATION OF CASE: A 71 years old lady presented with a painless right breast lump of a few months duration. Clinical examination revealed a 1.5â¯cm right breast upper outer quadrant mass. Axillary and systemic examinations were unremarkable. Mammogram showed an asymmetric density in the right upper outer quadrant which corresponded to a suspicious nodule measuring about 2â¯cm on the ultrasound. Ultrasound of the axilla showed an indeterminate right lymph node. Core needle biopsy of the right breast nodule showed ACC while the lymph node biopsy was non- metastatic. Staging scans did not reveal any definite distant metastasis. Her naso-endoscopy and MRI of the neck were normal. She underwent a right mastectomy and sentinel lymph node biopsy. Final histology returned as a grade II 55â¯mm ACC. Lympho-vascular invasion was absent. The tumour was triple negative for Estrogen receptor (ER), Progesterone receptor (PR) and Human epidermal receptor 2 (HER 2). Sentinel lymph node biopsy was negative for metastasis. She recovered well but declined adjuvant chemotherapy and radiation therapy. She is currently well 6 months post operation. DISCUSSION: ACC is an extremely rare subtype, therefore there are limited reports in literature on its imaging and pathological characteristics. Of this sparse data, there was no mention that there might be a big size discrepancy between the 2 modalities. This appreciable discrepancy has implications for pre-operative planning and the choice of breast surgery. It will be useful if the pathological extent of ACC could be determined more accurately radiologically. However, there are no distinctive imaging characteristics for ACC. ACC can appear as a smooth round mass similar to that of a benign mass or as an irregular mass on mammogram. On ultrasound, ACC often manifested as a hypo- echoic heterogeneous mass with minimal vascularity on Doppler imaging and may have an indistinct margin. MRI has a higher sensitivity than mammogram and ultrasound in determining the true extent of the tumour, but there remains little data on its usefulness in ACC. CONCLUSION: ACC can be extensively infiltrative and present much larger than its radiological size, as reported in our case. Use of better imaging modalities judiciously, in these cases, are needed to more accurately predict the true pathological size of ACC to prevent inadequate surgery.
RESUMEN
We report a case of Langerhans cell histiocytosis (LCH) occurring in the pelvis of a 2-year 11-month-old female with fluid-fluid level seen on MRI. Aspiration of the fluid during biopsy showed it to be blood with a few inflammatory cells and eosinophils. Tissue obtained during the biopsy confirmed the diagnosis to be LCH. While fluid-fluid levels have been infrequently encountered in skull lesions due to LCH, they have yet to be reported in lesions of the appendicular skeleton. The aim of this report is to familiarize radiologists with the fact that fluid-fluid levels can occur in LCH of the appendicular skeleton in children.
RESUMEN
ALK is an established causative oncogenic driver in neuroblastoma, and is likely to emerge as a routine biomarker in neuroblastoma diagnostics. At present, the optimal strategy for clinical diagnostic evaluation of ALK protein, genomic and hotspot mutation status is not well-studied. We evaluated ALK immunohistochemical (IHC) protein expression using three different antibodies (ALK1, 5A4 and D5F3 clones), ALK genomic status using single-color chromogenic in situ hybridization (CISH), and ALK hotspot mutation status using conventional Sanger sequencing and a next-generation sequencing platform (Ion Torrent Personal Genome Machine (IT-PGM)), in archival formalin-fixed, paraffin-embedded neuroblastoma samples. We found a significant difference in IHC results using the three different antibodies, with the highest percentage of positive cases seen on D5F3 immunohistochemistry. Correlation with ALK genomic and hotspot mutational status revealed that the majority of D5F3 ALK-positive cases did not possess either ALK genomic amplification or hotspot mutations. Comparison of sequencing platforms showed a perfect correlation between conventional Sanger and IT-PGM sequencing. Our findings suggest that D5F3 immunohistochemistry, single-color CISH and IT-PGM sequencing are suitable assays for evaluation of ALK status in future neuroblastoma clinical trials.
Asunto(s)
Neuroblastoma/genética , Neuroblastoma/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Quinasa de Linfoma Anaplásico , Animales , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Lactante , Recién Nacido , Ratones , Ratones Endogámicos BALB C , Mutación , Proteínas Tirosina Quinasas Receptoras/genéticaRESUMEN
AIM: To evaluate the clinicopathological features and treatment outcomes of cap polyposis in the pediatric population. METHODS: All pediatric patients with histologically proven diagnosis of cap polyposis were identified from our endoscopy and histology database over a 12 year period from 2000-2012 at our tertiary pediatric center, KK Women's and Children's Hospital in Singapore. The case records of these patients were retrospectively reviewed. The demographics, clinical course, laboratory results, endoscopic and histopathological features, treatments, and outcomes were analyzed. The study protocol was approved by the hospital institutional review board. The histological slides were reviewed by a pediatric histopathologist to confirm the diagnosis of cap polyposis. RESULTS: Eleven patients were diagnosed with cap polyposis. The median patient age was 13 years (range 5-17 years); the sample included 7 males and 4 females. All of the patients presented with bloody stools. Seven patients (63%) had constipation, while 4 patients (36%) had diarrhea. All of the patients underwent colonoscopy and polypectomies (excluding 1 patient who refused polypectomy). The macroscopic findings were of polypoid lesions covered by fibrinopurulent exudates with normal intervening mucosa. The rectum was the most common involvement site (n = 9, 82%), followed by the rectosigmoid colon (n = 3, 18%). Five (45%) patients had fewer than 5 polyps, and 6 patients (65%) had multiple polyps. Histological examination of these polyps showed surface ulcerations with a cap of fibrin inflammatory exudate. Four (80%) patients with fewer than 5 polyps had complete resolution of symptoms following the polypectomy. One patient who did not consent to the polypectomy had resolution of symptoms after being treated with sulphasalazine. All 6 patients with multiple polyps experienced recurrence of bloody stools on follow-up (mean = 28 mo). CONCLUSION: Cap polyposis is a rare and under-recognised cause of rectal bleeding in children. Our study has characterized the disease phenotype and treatment outcomes in a pediatric cohort.
Asunto(s)
Pólipos del Colon/complicaciones , Hemorragia Gastrointestinal/etiología , Pólipos/complicaciones , Enfermedades del Recto/complicaciones , Adolescente , Factores de Edad , Niño , Preescolar , Pólipos del Colon/patología , Pólipos del Colon/terapia , Colonoscopía , Procedimientos Quirúrgicos del Sistema Digestivo , Femenino , Fármacos Gastrointestinales/uso terapéutico , Hemorragia Gastrointestinal/patología , Hemorragia Gastrointestinal/terapia , Humanos , Masculino , Pólipos/patología , Pólipos/terapia , Enfermedades del Recto/patología , Enfermedades del Recto/terapia , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Crizotinib, a dual anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition (MET) tyrosine kinase inhibitor, is currently being evaluated for the treatment of neuroblastoma. Its effects are thought to be mediated mainly via its activity against ALK. Although MET genomic/protein expression status might conceivably affect crizotinib efficacy, this issue has hitherto not received attention in neuroblastomas. AIMS/METHODS: MET genomic and protein expression status was characterised by silver in situ hybridisation and immunohistochemistry (IHC) respectively, in a cohort of 54 neuroblastoma samples. MET splice isoforms were characterised in 15 of these samples by quantitative PCR. RESULTS: One case (1/54; prevalence 1.85%) displayed MET genomic amplification, while another case (1/54; prevalence 1.85%) displayed strong membranous MET protein expression (IHC score 3+). Alternative exon 10-deleted and exon 14-deleted MET splice isoforms were identified. CONCLUSIONS: MET amplification and protein expression, although low in prevalence, are present in neuroblastomas. This has implications when crizotinib is employed as a therapeutic agent in neuroblastomas. Additionally, the existence of alternatively spliced MET isoforms may have clinical and biological implications in neuroblastomas.
Asunto(s)
Neuroblastoma/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-met/metabolismo , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Empalme Alternativo , Quinasa de Linfoma Anaplásico , Línea Celular Tumoral , Niño , Preescolar , Crizotinib , Transición Epitelial-Mesenquimal , Exones/genética , Femenino , Genómica , Humanos , Hibridación in Situ , Lactante , Isoenzimas , Masculino , Mutación , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/genética , Neuroblastoma/patología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-met/genética , Pirazoles/farmacología , Piridinas/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Análisis de Matrices Tisulares , Resultado del TratamientoRESUMEN
We report a case of anaplastic large cell lymphoma (ALCL) showing aberrant expression of beta subunit of human chorionic gonadotrophin (beta-HCG). The patient was a 14-year-old boy who presented with a right inguinal mass and a raised serum beta-HCG level. Biopsy of the mass revealed a malignant neoplasm composed of large, pleomorphic cells with prominent nucleoli. These malignant cells showed positive staining with CD30, ALK, epithelial membrane antigen, and beta-HCG. Chromosomal analysis showed t(2;5)(p23;q35) translocation, and polymerase chain reaction demonstrated T-cell receptor gene rearrangement. The patient did not respond well to chemotherapy, and he died 8 months after the diagnosis. To the best of our knowledge, this is the 1st case of ALCL showing aberrant expression of beta-HCG and associated with a raised serum level of beta-HCG. We report this case to bring awareness of this presumably rare occurrence to avoid the risk of misdiagnosis.