Giant secretory multifocal adrenal myelolipoma: a diagnostic dilemma.

A 38-yearr-old man presented with erectile dysfunction and infertility. On examination, he was hypertensive and detected to have a left flank mass. Blood investigations were unremarkable except raised serum noradrenaline levels. Imaging revealed multiple well-defined fat-containing hypodense lesions in left suprarenal area with largest one measuring 14×16 cm, suggestive of left adrenal myelolipoma. Diagnostic dilemma was posed due to discordance between clinical, biochemical and imaging findings. Left adrenal mass resection was planned keeping the possibility of pheochromocytoma. However, histopathology revealed it to be adrenal myelolipoma. Hypertension was resolved in the postoperative period and serum noradrenaline levels were normalised. Final diagnosis of a secretary adrenal myelolipoma was made, which is an extremely rare entity.

An unusual diagnosis of paravertebral lesions: mediastinal myelolipoma.

BACKGROUND: Mediastinal myelolipoma is extremely rare. It is a benign nonfunctioning tumor composed of hematopoietic tissue and mature fatty tissue. Although computed tomography and magnetic resonance imaging are effective in diagnosing mediastinal myelolipoma, a definitive diagnosis is difficult to establish for rare extra-adrenal myelolipomas by imaging alone. Such tumors are often misdiagnosed as malignant retropleural liposarcoma, denoting a poor prognosis. Case presentation: We herein describe a 72-year-old man with multiple bilateral paravertebral mediastinal myelolipomas and discuss the imaging findings and differential diagnoses. We used a computed tomography-guided core biopsy to attain a preoperative diagnosis. Using this technique, we avoided an unnecessary surgical procedure for the patient's asymptomatic and relatively small lesions. CONCLUSIONS: Instead of biopsy by lesion excision, we advocate conducting a precisely targeted, minimally invasive computed tomography-guided core biopsy to obtain a definitive preoperative diagnosis and thus avoid unnecessary surgery for mediastinal myelolipoma, a benign nonfunctioning tumor.

Adrenocortical neoplasm of uncertain malignant potential with a myelolipomatous component.

Macroscopic fat inside an adrenal lesion on CT is pathognomonic for myelolipoma, a benign neoplasm. Without macroscopic fat, it can be difficult to discern the nature of an indeterminate adrenal mass on imaging. One possible diagnosis for an indeterminate lesion without macroscopic fat is an adrenal oncocytic neoplasm (AON). Despite its typical benign presentation cases of malignant AON have been reported. Patients with malignant AON are often not surgical candidates and survival for unresected disease is 20%-35%. We present the third report of an AON of uncertain malignant potential (AONUMP) associated with a macroscopic fatty component with the largest reported size and longest duration of follow-up in the literature. This report details diagnostic and therapeutic challenges posed by AONUMP. This case highlights how pathognomonic radiographical findings associated with benign myelolipoma might mask rare, potentially malignant, lipomatous tumours.

Bilateral adrenal myelolipoma in Cushing's disease: a relook into the role of corticotropin in adrenal tumourigenesis.

Adrenal myelolipomas are infrequently encountered benign tumours of unknown aetiology. In the majority of cases they are unilateral, and clinically and hormonally silent, only requiring periodic follow-up. However, bilateral adrenal myelolipomas are sometimes associated with endocrine disorders and warrant appropriate evaluation. Though the understanding of the pathophysiology of adrenal myelolipomas has long been elusive, adrenocorticotropic hormone (ACTH) has been proposed as the main tropic factor in a number of studies. Cushing's disease is rarely associated with bilateral and sometimes giant myelolipomas. In this article, the association of bilateral adrenal myelolipomas with Cushing's disease has been discussed and the role of ACTH in the tumourigenesis has been reviewed.

Characterization of lipid-rich adrenal tumors by FDG PET/CT: Are they hormone-secreting or not?

OBJECTIVES: The purpose of this study was to evaluate the diagnostic ability of FDG PET/CT to predict the hormone-secretion status of lipid-rich adrenal tumors. METHODS: This study included 29 lipid-rich (CT number <10 HU) adrenal tumors 2 cm or larger in diameter in 28 patients who underwent FDG PET/CT. The diagnoses were based on endocrine examinations, including adrenal venous sampling and subsequent surgical resection, or on the endocrinological and morphological imaging follow-up during a period of at least 6 months. The FDG uptake of the adrenal tumors was evaluated semi-quantitatively using maximum standardized uptake values (SUVmax) and a ratio of the adrenal SUVmax compared to the liver SUVmax (SUVratio) was used for comparison. The statistical significance of differences was assessed using the Mann-Whitney U test, and a p value <0.05 was considered to be statistically significant. RESULTS: The lipid-rich adrenal tumors were proved to be 16 non-hormone-secreting tumors (15 adenomas and one myelolipoma) and 13 hormone-secreting tumors (five subclinical cortisol-producing adenomas, six aldosterone-producing adenomas and two adenomas that produced both cortisol and aldosterone). None of the patients had pheochromocytoma or a malignant adrenal tumor. The SUVmax (median, range) of the hormone-secreting tumors (3.2, 2.0-8.3) was higher than that of the non-hormone-secreting tumors (2.4, 1.8-3.3) (p < 0.05). Similarly, the SUVratio of the hormone-secreting tumors (0.95, 0.70-3.10) was higher than that of the non-hormone-secreting tumors (0.72, 0.54-0.95) (p < 0.01). There was no significant difference in the tumor diameter between the two groups (p = 0.8). The sensitivity, specificity and accuracy of FDG PET/CT for differentiating hormone-secreting tumors from non-hormone-secreting tumors were 0.69, 0.81 and 0.76 for cutoff SUVratio of 0.8, and were 0.46, 1 and 0.76 for the cutoff SUVratio of 1.0, respectively. CONCLUSIONS: A lipid-rich adrenal tumor presenting increased FDG uptake compared with that of the liver is likely to be a hormone-secreting adenoma. Therefore, additional endocrinological investigations are strongly recommended when an FDG-avid lipid-rich incidentaloma is detected on FDG PET/CT.

Cell fusion in myeloma marrow microenvironment: role in tumor progression.

Multiple myeloma (MM) is a B cell malignancy characterized by uncontrolled expansion of malignant plasma cells within the bone marrow that contribute to formation of multiple osteolytic bone disease and severe skeletal devastation. Recently, direct and indirect observations suggest that fusion events between cells housed within the MM marrow microenvironment often occur and may play a role in tumor progression, including myeloma bone disease (MBD). A number of cells resident in the marrow, such as myeloid progenitors and dendritic cells, have inherited fusogenicity and osteoclastogenic potential due to the expression of a number of fusogenic proteins as well as a high sensitivity to fusogenic factors produced within the MM marrow milieu. Similarly, osteoclasts (OC), as bone-resorbing multinucleated cells resulting from the fusion of marrow monocyte/ macrophages, have been reported to improperly fuse with malignant plasma cells and drive transition of these cells into OC-like cells exerting bone-resorbing capacity. Further, based on indirect cytogenetic and molecular evidence, it has been proposed that MM cells may generate a hybrid progeny with high metastatic potential and drug resistance, ultimately pointing to uncontrolled homotypic fusions that accelerate MBD progression.

Thalidomide in total therapy 2 overcomes inferior prognosis of myeloma with low expression of the glucocorticoid receptor gene NR3C1.

PURPOSE: Because dexamethasone remains a key component of myeloma therapy, we wished to examine the impact of baseline and relapse expression levels of the glucocorticoid receptor gene NR3C1 on survival outcomes in the context of treatment with or without thalidomide. EXPERIMENTAL DESIGN: We investigated the clinical impact of gene expression profiling (GEP)-derived expression levels of NR3C1 in 351 patients with GEP data available at baseline and in 130 with data available at relapse, among 668 subjects accrued to total therapy 2 (TT2). RESULTS: Low NR3C1 expression levels had a negative impact on progression-free survival (PFS; HR, 1.47; P = 0.030) and overall survival (OS; HR, 1.90; P = 0.002) in the no-thalidomide arm. Conversely, there was a significant clinical benefit of thalidomide for patients with low receptor levels (OS: HR, 0.54; P = 0.015; PFS: HR, 0.54; P = 0.004), mediated most likely by thalidomide's upregulation of NR3C1. In the context of both baseline and relapse parameters, post-relapse survival (PRS) was adversely affected by low NR3C1 levels at relapse in a multivariate analysis (HR, 2.61; P = 0.012). CONCLUSION: These findings justify the inclusion of NR3C1 expression data in the work-up of patients with myeloma as it can significantly influence the choice of therapy and, ultimately, OS. The identification of an interaction term between thalidomide and NR3C1 underscores the importance of pharmacogenomic studies in the systematic study of new drugs.

Hierarchical regulation of mRNA partitioning between the cytoplasm and the endoplasmic reticulum of mammalian cells.

The mRNA transcriptome is currently thought to be partitioned between the cytosol and endoplasmic reticulum (ER) compartments by binary selection; mRNAs encoding cytosolic/nucleoplasmic proteins are translated on free ribosomes, and mRNAs encoding topogenic signal-bearing proteins are translated on ER-bound ribosomes, with ER localization being conferred by the signal-recognition particle pathway. In subgenomic and genomic analyses of subcellular mRNA partitioning, we report an overlapping subcellular distribution of cytosolic/nucleoplasmic and topogenic signal-encoding mRNAs, with mRNAs of both cohorts displaying noncanonical subcellular partitioning patterns. Unexpectedly, the topogenic signal-encoding mRNA transcriptome was observed to partition in a hierarchical, cohort-specific manner. mRNAs encoding resident proteins of the endomembrane system were clustered at high ER-enrichment values, whereas mRNAs encoding secretory pathway cargo were broadly represented on free and ER-bound ribosomes. Two distinct modes of mRNA association with the ER were identified. mRNAs encoding endomembrane-resident proteins were bound via direct, ribosome-independent interactions, whereas mRNAs encoding secretory cargo displayed predominantly ribosome-dependent modes of ER association. These data indicate that mRNAs are partitioned between the cytosol and ER compartments via a hierarchical system of intrinsic and encoded topogenic signals and identify mRNA cohort-restricted modes of mRNA association with the ER.

A "tumour trifecta:" myelolipomata arising within an adrenocortical adenoma ipsilateral to a synchronous clear cell renal cell carcinoma.

We present an intriguing case of adrenal myelolipomata occurring within an adrenocortical adenoma in concert with an ipsilateral clear cell renal cell carcinoma. A 50-year-old female presented with dull right flank pain and hematuria. Computed tomography indicated a 2.5 cm right renal mass as well as a 5 cm right adrenal mass. Both masses were surgically resected concurrently. Histology of the renal mass was consistent with conventional clear cell renal cell carcinoma, Fuhrman grade III. There was no extra-renal extension or lymphovascular invasion. The adrenal mass was a cortical adenoma with solid and nested patterns, with discrete zones consisting of erythroid, myeloid and megakaryocytic cells intermixed with mature adipocytes. Mitoses were inconspicuous. The solid tumour component was strongly positive for vimentin, inhibin and CD56, focally positive for low-molecular-weight cytokeratin (Cam 5.2), calretinin and CD10 (chiefly in the myelolipomatous zones), and negative for chromogranin, S100, HMB-45, melan-A (A103), Mart-1, synaptophysin, SMA, CK7, CK20, ER, PR, TTF-1, CD99 and GCDFP (BRST-2). Ki67 (MIB1) staining indicated a low tumour proliferation index. Although well-described individually, a search of the English language literature suggests that this is the first such documented case of synchrony of these three lesions. We also present a relevant review of the literature pertaining to adrenal lesions. In particular, we emphasize the epidemiological, histological and immunohistochemical features that are helpful in determining the origin and malignant potential of adrenal lesions.

Renal sinus myelolipoma coexistent with renal pelvis papillary transitional cell carcinoma: a case report.

A unique case of renal sinus myelolipoma presenting as a mass coexistent with papillary transitional cell carcinoma is reported. The patient was a 64-year-old man with a history of bladder transitional cell carcinoma. He presented with gross hematuria and a filling defect in the renal pelvis on computed tomography scan. Pathological findings revealed an irregular myxoid fatty mass, in addition to high-grade papillary transitional cell carcinoma. The differential diagnosis included myxoid liposarcoma, myxoid variant of malignant fibrous histiocytoma (myxofibrosarcoma), and angiomyolipoma. Immunoperoxidase staining confirmed the presence of hematopoietic cells, whereas diagnostic histological and immunohistochemical features of liposarcoma, myxofibrosarcoma, and angiomyolipoma were absent. Myelolipoma and papillary transitional cell carcinoma appear to be unrelated coexistent entities in this case.

Lack of ACTH and androgen receptor expression in a giant adrenal myelolipoma associated with 21-hydroxylase deficiency.

Myelolipomas of the adrenal gland are benign, nonfunctioning tumors. Patients with congenital adrenal hyperplasia sometimes develop large and bilateral myelolipomas. Although the precise pathogenesis of myelolipomas remains unclear, prolonged stimulation with high levels of adrenocorticotropic hormone (ACTH) or adrenal androgens are assumed to have a causative role. To clarify the role of ACTH and androgen in the pathogenesis of myelolipoma, we report a case of giant adrenal myelolipoma in a patient with poorly controlled congenital adrenal hyperplasia. A 43-year-old female was diagnosed with congenital adrenal hyperplasia at 6 years of age because of ambiguous genitalia. She had high plasma ACTH and 17-hydroxyprogesterone levels. Abdominal computed tomography showed a huge mass on the left adrenal gland, and an enlarged right adrenal mass. Genetic testing for CYP21A2 was performed and revealed that her genotype was IVS2-13A/C>G/I172N. Adrenalectomy for the left-side tumor was performed. Histological study revealed that the tumor consisted of fat cells and myeloid components, findings compatible with adrenal myelolipoma. Neither ACTH receptors nor androgen receptor was over-expressed in the tumor. Our finding that the tumor did not over-express ACTH or androgen receptor suggests a limited direct role for these hormones in the development of the myelolipoma.

Adrenocortical carcinoma with concomitant myelolipoma in a patient with hyperaldosteronism.

We present a case of aldosterone-secreting adrenocortical carcinoma with concomitant myelolipoma. To the best of our knowledge, this is the first such reported case. The patient was a 43-year-old man with severe hypertension. Clinical workup revealed an increased serum aldosterone level, hypokalemia, and metabolic alkalosis, and a left adrenal mass was found on computed tomography. The patient underwent a unilateral adrenalectomy, which led to improvement in blood pressure, the serum potassium level, and aldosterone concentration. The tumor weighed 70 g and measured 5.0 cm. On microscopic examination, we found necrosis, focal cytologic atypia, diffuse eosinophilic cells comprising more than 75% of the tumor, 5 to 7 mitotic figures per 50 high-power fields, rare atypical mitosis, and venous invasion. At the periphery of the tumor but within the capsule, microscopic areas of myelolipoma were seen. Ki-67 staining was positive in 20% of the tumor cells. Although rare, aldosterone-secreting carcinoma associated with myelolipoma should be included in the differential diagnosis of adrenal gland masses.

Defective apoptosis as potential mechanism in the tumorogenesis of myelolipoma.

Apoptosis is considered an important mechanism of selective deletion that occurs during hematopoiesis. Myelolipoma is a rare benign tumor composed of adipose tissue and hematopoietic cells. The pathogenesis of this benign tumor is still unclear. Analysing the structural levels and apoptosis of normal human bone marrow (NHBM) and human myelolipoma (HM), the apoptotic events resulted abundantly present in NHBM compared to HM, which showed a small number of apoptotic cells. By contrast, Fas expression was strongly present both in NHBM and HM. These findings suggest that an altered function of Fas in myelolipoma is not able to trigger the apoptotic machinery. In conclusion, we hypothesize that drastic reduction of apoptosis in myelolipoma can be considered one of the growth regulatory mechanisms.