Complete Radiological Response of Recurrent Metastatic Adrenocortical Carcinoma to Pembrolizumab and Mitotane

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Treatment options for ACC are limited, with resection the main intervention. Most cases present in late metastatic cases, and data regarding effective therapies is limited. We report a case of ACC in a 40-year-old woman with history of ACC postadrenalectomy, who presented with recurrent metastatic ACC in the left perinephric space. She was started on pembrolizumab which was added to her mitotane maintenance therapy. Complete radiological response was achieved after 4 cycles of pembrolizumab. As far as we know, this is the first case to achieve complete radiological response with mitotane and pembrolizumab in recurrent metastatic ACC, with negative prognostic markers and no prior radiotherapy. As our findings are in the setting of one clinical case, we suggest the need to perform a trial to assess the benefit of combining mitotane and pembrolizumab in treating metastatic ACC.

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Adrenocortical carcinoma arising from an adrenal adenoma in a young adult female

Journal of Surgical Case Reports ◽

10.1093/jscr/rjz200 ◽

2019 ◽

Vol 2019 (7) ◽

Cited By ~ 1

Author(s):

Monica E Rebielak ◽

Mary R Wolf ◽

Rebecca Jordan ◽

Jacqueline C Oxenberg

Keyword(s):

Young Adult ◽

Surgical Resection ◽

Adult Female ◽

Adrenocortical Carcinoma ◽

Poor Prognosis ◽

Adrenal Adenoma ◽

Adrenal Incidentaloma ◽

Adjuvant Radiation ◽

History Of ◽

Rare Malignancy

Abstract Adrenocortical carcinoma (ACC) is a rare malignancy that often carries a poor prognosis whereas adrenal incidentalomas are relatively common findings on imaging. Although most adrenal lesions are benign, 15% of patients with ACC are diagnosed based on workup for an adrenal incidentaloma. Continued surveillance or surgical resection may be recommended depending on size. The risk of a benign, non-functional adrenal lesion becoming malignant is low. Therefore, adrenal lesions typically undergo surveillance for no more than 2 years in patients with stable findings and no history of malignancy. This case describes a young adult female with a benign left adrenal adenoma who was found to have high grade ACC 7 years later. Based on interval size increase with indeterminate density, patient underwent surgical resection with adjuvant radiation and medical therapy.

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Oncological Frontiers in the Treatment of Malignant Pleural Mesothelioma

Journal of Clinical Medicine ◽

10.3390/jcm10112290 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2290

Author(s):

Emanuele Vita ◽

Alessio Stefani ◽

Mariantonietta Di Di Salvatore ◽

Marco Chiappetta ◽

Filippo Lococo ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Poor Prognosis ◽

Treatment Options ◽

Genomic Sequencing ◽

Pleural Mesothelioma ◽

Targeted Drugs ◽

Treatment Algorithms ◽

Rare Malignancy ◽

New Generation ◽

The Way

Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by very poor prognosis and lack of treatment options. Immunotherapy has rapidly emerged as an effective tool for MPM, particularly for tumors of non-epithelioid histology. At the same time, comprehensive genomic sequencing may open the way to new-generation targeted-drugs able to hit specific MPM molecular vulnerabilities. These innovations will possibly enrich, but also dramatically complicate, the elucidation of treatment algorithms. Multidisciplinary integration is urgently needed.

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MANAGEMENT OF ENDOCRINE DISEASE: Adrenocortical carcinoma: differentiating the good from the poor prognosis tumors

Acta Endocrinologica ◽

10.1530/eje-18-0027 ◽

2018 ◽

Vol 178 (5) ◽

pp. R215-R230 ◽

Cited By ~ 23

Author(s):

Anne Jouinot ◽

Jérôme Bertherat

Keyword(s):

Adrenocortical Carcinoma ◽

Poor Prognosis ◽

Tumor Biology ◽

Tumor Grade ◽

Proliferation Index ◽

Adrenal Tumors ◽

Molecular Alterations ◽

Recurrent Mutations ◽

Genomic Studies ◽

Rare Malignancy

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis, the five-years overall survival being below 40%. However, there is great variability of outcomes and we have now a better view of the heterogeneity of tumor aggressiveness. The extent of the disease at the time of diagnosis, best assayed by the European Network for the Study of Adrenal Tumors (ENSAT) Staging Score, is a major determinant of survival. The tumor grade, including the mitotic count and the Ki67 proliferation index, also appears as a strong prognostic factor. The assessment of tumor grade, even by expert pathologists, still suffers from inter-observer reproducibility. The emergence of genomics in the last decade has revolutionized the knowledge of molecular biology and genetics of cancers. In ACC, genomic approaches – including pan-genomic studies of gene expression (transcriptome), recurrent mutations (exome or whole-genome sequencing), chromosome alterations, DNA methylation (methylome), miRNA expression (miRnome) – converge in a new classification of ACC, characterized by distinct molecular profiles and very different outcomes. Targeted measurements of a few discriminant molecular alterations have been developed in the perspective of clinical routine, and thus, may help defining therapeutic strategy. By individualizing patients’ prognosis and tumor biology, these recent progresses appear as an important step forward towards precision medicine.

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First Case Report of an Unusual Fungus (Sporopachydermia lactativora) Associated with a Pulmonary Infection in a Drug Injection User

Clinical Pathology ◽

10.1177/2632010x211029970 ◽

2021 ◽

Vol 14 ◽

pp. 2632010X2110299

Author(s):

Hiba A Al Dallal ◽

Siddharth Narayanan ◽

Christopher M Jones ◽

Shawn R Lockhart ◽

James W Snyder

Keyword(s):

Case Report ◽

Treatment Options ◽

Pathogenic Fungi ◽

First Case ◽

New Information ◽

The Matrix ◽

Potential Pathogen ◽

Physician Awareness ◽

History Of ◽

Polysubstance Abuse

In contrast to a robust literature on known pathogenic fungi such as Cryptococcus and Aspergillus species that cause pulmonary infections, reports of the uncommon genus Sporopachydermia causing infections are very limited. We present the first case report describing the fungus, Sporopachydermia lactativora as a likely cause of pneumonia in a patient with a history of polysubstance abuse and injection drug use (IDU). The patient recovered following antifungal treatment. The organism was recovered from a blood culture, 3 days post collection. Although CHROMagar was of little value, only yeast-like organisms were observed on cornmeal agar. The organism was not in the matrix-assisted laser desorption/ionization—time of flight (MALDI-TOF) mass spectrometry database. Definitive identification was achieved using the ribosomal DNA (rDNA) sequence analysis by targeting the ITS1 (internal transcribed spacer 1) region. This case report is intended to promote awareness of this fungus as a potential pathogen, by providing new information that has not yet been reported in the literature, and prompts physician awareness to suspect a fungal infection when managing patients with a history of IDU as a potential source of unique environmental organisms not previously encountered, warranting more comprehensive diagnosis and treatment options.

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Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms22031238 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1238

Author(s):

Vania Balderrama Brondani ◽

Amanda Meneses Ferreira Lacombe ◽

Beatriz Marinho de Paula Mariani ◽

Luciana Montenegro ◽

Iberê Cauduro Soares ◽

...

Keyword(s):

Protein Expression ◽

Adrenocortical Carcinoma ◽

Prognostic Markers ◽

Cox Regression ◽

Free Survival ◽

Low Protein ◽

Dismal Prognosis ◽

Protein Expressions ◽

Genomic Studies ◽

Rare Malignancy

Adrenocortical carcinoma (ACC) is a rare malignancy that is associated with a dismal prognosis. Pan-genomic studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenocortical tumorigenesis. Our aims were to evaluate the protein expression of ATRX and ZNRF3 in a cohort of 82 adults with ACC and to establish their prognostic value. Two pathologists analyzed immuno-stained slides of a tissue microarray. The low protein expression of ATRX and ZNRF3 was associated with a decrease in overall survival (OS) (p = 0.045, p = 0.012, respectively). The Cox regression for ATRX protein expression of >1.5 showed a hazard ratio (HR) for OS of 0.521 (95% CI 0.273–0.997; p = 0.049) when compared with ≤1.5; for ZNRF3 expression >2, the HR for OS was 0.441 (95% CI, 0.229–0.852; p = 0.015) when compared with ≤2. High ATRX and ZNRF3 protein expressions were associated with optimistic recurrence-free survival (RFS) (p = 0.027 and p = 0.005, respectively). The Cox regression of RFS showed an HR of 0.332 (95%CI, 0.111–0.932) for ATRX expression >2.7 (p = 0.037), and an HR of 0.333 (95%CI, 0.140–0.790) for ZNRF3 expression >2 (p = 0.013). In conclusion, low protein expression of ATRX and ZNRF3 are negative prognostic markers of ACC; however, different cohorts should be evaluated to validate these findings.

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Natural History of Patients with Unresectable Cholangiocarcinoma

Journal of Digestive Endoscopy ◽

10.1055/s-0040-1709277 ◽

2019 ◽

Vol 10 (04) ◽

pp. 206-209

Author(s):

Sudhakar A. ◽

Sravan Kumar K. ◽

L. R.S. Girinadh ◽

P. MuraliKrishna

Keyword(s):

Natural History ◽

Poor Prognosis ◽

Bile Ducts ◽

Andhra Pradesh ◽

Treatment Options ◽

Hepatic Malignancy ◽

History Of

AbstractCholangiocarcinoma is a malignancy of the bile ducts. Globally, CCA is the second most common primary hepatic malignancy. These tumors usually progress insidiously, are difficult to diagnose, and have poor prognosis. Unfortunately, treatment options are discouraging. Data on the natural history of CCA in coastal Andhra Pradesh is limited. Our aim is to report the natural history of CCA in this region.

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Recurrent Cholangiocarcinoma in Pregnancy: A Case Report

American Journal of Perinatology Reports ◽

10.1055/s-0038-1675376 ◽

2018 ◽

Vol 08 (04) ◽

pp. e261-e263

Author(s):

Antonia Francis ◽

Michelle Chang ◽

Cara Dolin ◽

Judith Chervenak ◽

Elyce Cardonick

Keyword(s):

Palliative Care ◽

Poor Prognosis ◽

Treatment Options ◽

Clinical Scenario ◽

Medical Support ◽

Ethical Considerations ◽

First Case ◽

Obstetrical Patient ◽

Behavioral Sequelae ◽

In Pregnancy

AbstractHepatobiliary malignancies during pregnancy are extremely rare and portend a poor prognosis. There are only seven published cases of cholangiocarcinoma in an obstetrical patient, all are cases of primary cholangiocarcinoma (1–7). Herein, we describe the first case of recurrent cholangiocarcinoma during pregnancy. The patient did not receive chemotherapy during pregnancy and required prolonged hospitalizations for nutritional and intensive medical support. She delivered preterm, at 30 2/7 weeks gestation, after developing pre-eclampsia with severe features. The infant was healthy, with no malformations, and currently exhibits no neurological or behavioral sequelae at 8months of age. We discuss themanagement considerations inherent to this complex clinical scenario including metastatic disease severity, ethical considerations, and palliative care treatment options.

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Pharyngeal pouch management: an historical review

The Journal of Laryngology & Otology ◽

10.1017/s0022215115002285 ◽

2015 ◽

Vol 130 (2) ◽

pp. 116-120 ◽

Cited By ~ 9

Author(s):

K Stewart ◽

P Sen

Keyword(s):

Treatment Options ◽

Case Series ◽

Historical Review ◽

The Elderly ◽

Pharyngeal Pouch ◽

Elderly Age ◽

Current Management ◽

First Case ◽

History Of ◽

Nineteenth And Twentieth Centuries

AbstractBackground:Management of the pharyngeal pouch has evolved enormously since the first description by Ludlow in 1764 and the first case series by Zenker and Von Ziemssen in 1877. With the introduction of antibiotics, and the advancement of surgical technique with the advent of endoscopic surgery and lasers, current management is vastly different to that in the nineteenth century.Objectives:This paper traces the history of pharyngeal pouch management, and discusses the various treatment options and opinions recorded during the nineteenth and twentieth centuries, comparing these with techniques popular today.Results and conclusion:Pharyngeal pouch surgery has been associated with significant morbidity, both because of the elderly age of patients typically affected by the condition and because of the surgery itself and potential post-operative complications encountered. The historical development of pharyngeal pouch management and the understanding of pharyngeal pouch pathophysiology are discussed.

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Stimulated Expression of CXCL12 in Adrenocortical Carcinoma by the PPARgamma Ligand Rosiglitazone Impairs Cancer Progression

Journal of Personalized Medicine ◽

10.3390/jpm11111097 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1097

Author(s):

Giulia Cantini ◽

Laura Fei ◽

Letizia Canu ◽

Elena Lazzeri ◽

Mariangela Sottili ◽

...

Keyword(s):

Tumor Growth ◽

Cancer Progression ◽

Adrenocortical Carcinoma ◽

Treatment Options ◽

Tumor Development ◽

Cxcl12 Expression ◽

Physiological Conditions ◽

Chemokine Cxcl12 ◽

Rare Malignancy

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis when metastatic and scarce treatment options in the advanced stages. In solid tumors, the chemokine CXCL12/CXCR4 axis is involved in the metastatic process. We demonstrated that the human adrenocortex expressed CXCL12 and its cognate receptors CXCR4 and CXCR7, not only in physiological conditions, but also in ACC, where the receptors’ expression was higher and the CXCL12 expression was lower than in the physiological conditions. In a small pilot cohort of 22 ACC patients, CXCL12 negatively correlated with tumor size, stage, Weiss score, necrosis, and mitotic activity. In a Kaplan–Meier analysis, the CXCL12 tumor expression significantly predicted disease-free, progression-free, and overall survival. In vitro treatment of the primary ACC H295R and of the metastatic MUC-1 cell line with the PPARγ-ligand rosiglitazone (RGZ) dose-dependently reduced proliferation, resulting in a significant increase in CXCL12 and a decrease in its receptors in the H295R cells only, with no effect on the MUC-1 levels. In ACC mouse xenografts, tumor growth was inhibited by the RGZ treatment before tumor development (prevention-setting) and once the tumor had grown (therapeutic-setting), similarly to mitotane (MTT). This inhibition was associated with a significant suppression of the tumor CXCR4/CXCR7 and the stimulation of human CXCL12 expression. Tumor growth correlated inversely with CXCL12 and positively with CXCR4 expression, suggesting that local CXCL12 may impair the primary tumor cell response to the ligand gradient that may contribute to driving the tumor progression. These findings indicate that CXCL12/CXCR4 may constitute a potential target for anti-cancer agents such as rosiglitazone in the treatment of ACC.

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SUN-179 Oncocytic Adrenocortical Carcinoma: A Case Report

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1942 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Jessica Chan ◽

Arthur A Fusco

Keyword(s):

Case Report ◽

Adrenocortical Carcinoma ◽

Poor Prognosis ◽

Adrenal Mass ◽

Left Kidney ◽

Proliferation Index ◽

Ki 67 ◽

Oncocytic Variant ◽

Rare Malignancy ◽

Minor Criteria

Abstract Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Oncocytic variant of adrenocortical carcinoma is considered to be an even more rare malignancy with four reported in the literature in 2002 and thirty-six documented in 2015 i ii. This case report illustrates the case of oncocytic ACC. A 40-year-old woman post-hysterectomy from cervical cancer presented to the ER with severe left flank and back pain for two weeks. There was no weight loss or early satiety. CT scan revealed a large left adrenal mass measuring 12x9x13 cm, displacing the left kidney inferiorly with no metastasis to nearby structures. We ruled out functional adrenal mass through a 24-hour urine collection and blood work, then performed open left adrenalectomy. Grossly, it was a large, tan-colored mass, weighing approximately 2,500 grams. On biopsy, we incidentally found the mass to be oncocytic adrenocortical carcinoma. Using the Lin-Weiss-Bisceglia criteria, it met two major and one minor criteria, when only one major criterion is required to indicate malignancy. Immunohistochemical stains showed that the tumor cells were positive for Mart-1, inhibin, and synaptophysin. Quantitative Ki-67 showed a proliferation index of 10% in average (>5% is considered malignant). Even though adrenocortical carcinoma, specifically the oncocytic variant of ACC, is a very rare occurrence, it should be on the differential diagnosis for a chief complaint of unilateral flank pain with a large adrenal mass on CT due to its poor prognosis. Endnotes i Hoang, M., Ayala, A. & Albores-Saavedra, J. Oncocytic Adrenocortical Carcinoma: A Morphologic, Immunohistochemical and Ultrastructural Study of Four Cases. Mod Pathol 15, 973-978 (2002) doi:10.1038/modpathol.3880638 ii Kalra S, Manikandan R, Srinivas BH. Oncocytic adrenocortical carcinoma--a rare pathological variant. BMJ Case Rep. 2015;2015:bcr2014208818. Published 2015 Apr 24. doi:10.1136/bcr-2014-208818

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