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BACKGROUND: Malignant mixed corticomedullary adrenal tumors (MCMTs) are extremely rare, with limited cases reported in the literature. The pathophysiology of malignant MCMTs is not well understood; the most prevailing theories are that it is a composite tumor of embryologically derived mesodermal (adrenal cortex) and neural crest (medulla) origin, perpetuating as two distinct cell lines forming a singular mass. Clinical features and laboratory diagnosis are associated with hypersecretions of the adrenal cortex and medulla. Surgical resection is curative in an isolated tumor. We reviewed and compared cases in the literature highlighting the pathogenesis and genetics of benign and malignant MCMT. METHODS: Comprehensive literature analysis was conducted on PubMed and all the cases of mixed corticomedullary adrenal tumor published in English were included. RESULTS: Most patients were female (73.1%) with a median age of 49 in women and 50 in men. Surgery was performed in all patients, and in four patients with malignant disease, chemotherapy was used as well. Clinically, most patients presented with hypertension (69%) followed by Cushing syndrome (42%) and diabetes (19%). Tumors often produced cortisol (74%), catecholamines (50%), and adrenocorticotrophic hormone (ACTH) (38%), with lower incidence of aldosterone- (7%) or dopamine (4%)-producing tumors. Immunohistochemical staining of 96% of cases showed Chromogranin-A (73%) and Synaptophysin (62%), followed by Inhibin-α (50%), Melan-A (31%), and S-100 (23%). Of the reported four cases with malignant disease, three showed a Ki-67 index of 40-50% with one showing less than 5%. CONCLUSION: Mixed corticomedullary adrenal tumors rarely present as a malignant disease requiring chemotherapy. Most MCMTs confer a good prognosis and respond well to surgical resection, though their pathogenesis is largely up to speculation because of limited data. Current theories regarding MCMT pathogenesis should be investigated further with genetic testing. Future research on MCMT may provide ways to guide physician diagnosis and subsequent treatment for refractory cases.
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Pulmonary carcinoid tumors are a rare subtype of neuroendocrine cell tumor found in approximately 1-2% of lung cancers. Management is primarily through surgical resection, with limited benefit of adjuvant therapy in the clinical setting. Genomic profiling is in the nascent stages to molecularly classify these tumors, but there are promising insights for future targeted therapy. A total of 80 abstracts were analyzed for further review with 11 included in our final analysis. Only 4 of the 11 reviewed in depth provided statistical analysis. We evaluated PFS, OS, 1- and 5-year survival as mentioned in the studies. Nodal and KI67 status were also analyzed. Based on the current literature, there is no definitive evidence that adjuvant chemotherapy after resection confers a survival benefit in typical or atypical carcinoids.
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Autophagy has been of novel interest since it was first demonstrated to have effect in Burkitt's lymphoma. Since that time, the autophagy agents chloroquine and hydroxychloroquine have become the only FDA (Food and Drug Administration)-approved autophagy inhibitors. While not approved for cancer therapy, there are ongoing clinical trials to evaluate their safety and efficacy. Pevonedistat has emerged as a novel inhibitor through the neddylation pathway and is an autophagy activator. This paper summarizes and presents current clinical trials for hydroxychloroquine (HCQ), chloroquine (CQ), and Pevonedistat for the clinician.
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Hidroxicloroquina , Neoplasias , Autofagia , Cloroquina/farmacología , Cloroquina/uso terapéutico , Humanos , Hidroxicloroquina/farmacología , Hidroxicloroquina/uso terapéutico , Neoplasias/tratamiento farmacológico , Estados UnidosRESUMEN
Pancytopenia is a decrease across cellular hematological lines. Many different etiologies can cause this clinical picture including viral and bacterial infections, chemicals, malignancy, and medications. Particular attention should be paid to the onset, timing, and severity as they can indicate the underlying cause. In cases of iatrogenic-induced pancytopenia, the offending agent should be stopped immediately and the patient should be monitored for recovery of cell lines. While not well reported in the literature, trimethoprim-sulfamethoxazole (TMP-SMX) is a cause of pancytopenia. We present a case of drug-induced pancytopenia secondary to TMP-SMX that resolved quickly with cessation of use.
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The notochord is the defining structure of all chordate embryos. It is a midline structure ventral to the ectoderm, neural plates, and neural arch. Remnants of the notochord ultimately give rise to the nucleus pulposus. The function of the notochord is to organize the surrounding structures. Chordoma is a rare malignant bone tumor arising from remnants of the notochord. These tumors are indolent and can present as incidental or locally advanced involving adjacent structures. These tumors typically present at the skull base and sacral spine but more rarely can be seen on the cervical and thoracic spine. Rare cases of chordoma invading the brachial plexus have been recorded. Surgical resection is the mainstay of treatment for chordomas. We would like to discuss a novel presentation of a chordoma as a Pancoast tumor, and aim to highlight the clinical importance of accurate diagnosis and planning therapy along with poor prognosis of incomplete surgical resection.
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Secondary organizing pneumonia refers to a disease process caused by pulmonary tissue injury. Various insults can cause secondary organizing pneumonia, including multiple types of infections and cancer. The mainstay of diagnosis is a combination of imaging and lung biopsy showing inflammatory changes, specifically plugs with granulated tissue and fibrosis. Clinical suspicion needs to be raised for secondary organizing pneumonia when a patient is requiring increasing amounts of oxygen in the presence of treatment for pneumonia or another underlying lung disease. Here, we present the case of a 65-year-old male who presented with acute hypoxemic respiratory failure in the setting of previously having been tested positive for influenza B. Aggressive steroids with eventual tapering of his O2 requirements led to a successful outcome. While influenza has been reported as a cause of secondary organizing pneumonia after proceeding infection, these cases are usually represented by type A, rather than B.
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Bartter syndrome is a rare disorder that is characterized by weakness and fatigue with laboratory findings of hypokalemia and metabolic alkalosis with increased aldosterone and angiotensin. It specifically acts on the ascending loop of Henle, characterized by miscoded proteins affecting NaCl transports and channels. Patients will require replacement of potassium and sometimes magnesium due to the kidneys' inability to reabsorb these ions. So what happens when the body's other primary mechanism of absorption of these elements are taken out? In this article, we present the case of a 47-year-old woman with Bartter syndrome on oral potassium 40 mg BID (twice a day) and magnesium oxide 800 TID (thrice a day), who recently had a small bowel resection that required intravenous potassium and magnesium throughout her hospital admission. Significant questions arose as to how her electrolytes should be managed, given her unusual presentation with rare underlying disorder. We discuss the implications of her bowel resection in the context of Bartter syndrome and our views on her future course based on available literature.
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Alcalosis , Síndrome de Bartter , Hipopotasemia , Alcalosis/etiología , Síndrome de Bartter/complicaciones , Femenino , Humanos , Hipopotasemia/etiología , Riñón , Magnesio , Persona de Mediana EdadRESUMEN
Indoleamine 2,3 dioxygenase (IDO), first discovered in the 1960s, is an enzyme that has become a highly investigated metabolic target in cancer research. IDO is the rate-limiting step in tryptophan metabolism catabolism into its byproducts - kynurenines. Both IDO and kynurenines have been implicated in altering the tumor microenvironment, allowing for a tolerogenesis by affecting T-cell maturation and proliferation, and more specifically by inducing differentiation into T regulatory cells. Two mechanisms have been suspected in creating this environment: tryptophan starvation and metabolite toxicity. IDO has been shown to be expressed not only in cancer cells but also in antigen-presenting cells. The exact mechanisms underlying the two different sites of expression have not been fully elucidated. To date, most literature has focused on the role of IDO in solid tumors; we provide a review of IDO and its impact on hematological malignancies - more specifically, acute myeloid leukemia. The pathophysiology of IDO will be discussed, including a summarization of the literature to date on how IDO expression effects prognosis and disease progression in acute myeloid leukemia, along with current IDO-specific therapeutics with future considerations.
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Antineoplásicos/farmacología , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Leucemia Mieloide Aguda/inmunología , Microambiente Tumoral/inmunología , Antineoplásicos/uso terapéutico , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , Células Dendríticas/enzimología , Células Dendríticas/inmunología , Progresión de la Enfermedad , Regulación Leucémica de la Expresión Génica/inmunología , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Quinurenina/metabolismo , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Pronóstico , Supervivencia sin Progresión , Procesamiento Proteico-Postraduccional/inmunología , Tasa de Supervivencia , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Triptófano/metabolismo , Escape del Tumor/efectos de los fármacos , Escape del Tumor/inmunología , Microambiente Tumoral/efectos de los fármacos , Regulación hacia Arriba/inmunologíaRESUMEN
Chronic myelogenous leukemia (CML) is a hematopoietic disorder caused by the BCR/ABL gene or Philadelphia chromosome. The first Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor for treatment of CML was imatinib in 2001. Since then, multiple therapies, such as nilotinib, dasatinib, bosutinib, and, more recently, ponatinib, have made their way as viable treatment options for first-line and secondary therapies. Most patients tend to respond to first-line treatment. Although there is a subset of patients who do not achieve complete molecular response with first line, newer options have proven beneficial. As we progress through therapies, there still remain some patients who do not adequately respond to current available therapies. The treatment options and guidelines become more difficult in such situations, not only with respect to cost but also patient quality of life and satisfaction. We discuss a 75-year-old white female with CML, who has had multiple therapies with hematological remission but has never achieved complete molecular remission, currently on bosutinib and tolerating it well.
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Ruxolitinib has become a new therapeutic option for steroid refractory graft-versus-host disease (srGVHD), with a substantial remission rate. Its anti-inflammatory properties by blocking interleukin pathways have made it a novel therapeutic approach to inflammatory disease processes, such as GVHD. The long-term use of ruxolitinib has not been explicitly studied outside the context in the treatment of multiple myeloma. With current clinical trials underway for the use of ruxolitinib in srGVHD, there are still no current guidelines or protocols for long-term clinical use. Of the available literature showing ruxolitinib utilization for srGVHD, most cases lead to resolution and eventual discontinuation. We present a case of a 32-year-old male on ruxolitinib with GVHD status postmatched unrelated donor stem cell transplant (MUD SCT) for acute myeloid leukemia (AML) with FLT3 mutation currently on ruxolitinib for 5 years who is not able to tolerate reduction in dosage due to flare-ups. We discuss the clinical implications and nuance of therapy with ruxolitinib with unknown long-term effects and weigh the risks and benefits.
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PET/CT scans are frequently used in the initial workup of suspicious lesions but not all that lights up on a PET is cancerous. We wish to discuss a case of silicone-induced granuloma mimicking malignancy and the role of other imaging modalities for further workup.
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PURPOSE: To calculate the output factor (OPF) of any irregularly shaped electron beam at extended SSD. METHODS: Circular cutouts were prepared from 2.0 cm diameter to the maximum possible size for 15 × 15 applicator cone. In addition, two irregular cutouts were prepared. For each cutout, percentage depth dose (PDD) at the standard SSD and doses at different SSD values were measured using 6, 9, 12, and 16 MeV electron beam energies on a Varian 2100C LINAC and the distance at which the central axis electron fluence becomes independent of cutout size was determined. The measurements were repeated with an ELEKTA Synergy LINAC using 14 × 14 applicator cone and electron beam energies of 6, 9, 12, and 15 MeV. The PDD measurements were performed using a scanning system and two diodes-one for the signal and the other a stationary reference outside the tank. The doses of the circular cutouts at different SSDs were measured using PTW 0.125 cm(3) Semiflex ion-chamber and EDR2 films. The electron fluence was measured using EDR2 films. RESULTS: For each circular cutout, the lateral buildup ratio (LBR) was calculated from the measured PDD curve using the open applicator cone as the reference field. The effective SSD (SSDeff) of each circular cutout was calculated from the measured doses at different SSD values. Using the LBR value and the radius of the circular cutout, the corresponding lateral spread parameter [σR(z)] was calculated. Taking the cutout size dependence of σR(z) into account, the PDD curves of the irregularly shaped cutouts at the standard SSD were calculated. Using the calculated PDD curve of the irregularly shaped cutout along with the LBR and SSDeff values of the circular cutouts, the output factor of the irregularly shaped cutout at extended SSD was calculated. Finally, both the calculated PDD curves and output factor values were compared with the measured values. CONCLUSIONS: The improved LBR method has been generalized to calculate the output factor of electron therapy at extended SSD. The percentage difference between the calculated and the measured output factors of irregularly shaped cutouts in a clinical useful SSD region was within 2%. Similar results were obtained for all available electron energies of both Varian 2100C and ELEKTA Synergy machines.