Primary adrenal lymphoma (PAL) is a rare entity that presents as unilateral or bilateral rapidly growing adrenal masses, with signs and symptoms most commonly related to adrenal insufficiency due to the mass effect on the surrounding tissues. Although steroeidogenesis has not been previously described in PAL, we herein report two cases of PAL presenting as adrenal incidentalomas (AIs) that demonstrated autonomous cortisol production. A 52-year-old woman presented with lumbar pain; a computed tomography (CT) scan demonstrated a left AI measuring 8.5 × 15 × 10 cm. Similarly, an 80-year-old woman presented with lumbar pain, demonstrating in a CT scan a bilateral AI (right: 9 × 6.5 cm, left: 3.6 × 3.2 cm). Both cases underwent a full hormonal evaluation according to the algorithm for the investigation of AIs, demonstrating increased 24-h cortisol excretion, suppressed fasting adrenocorticotropic hormone (ACTH) levels, and non-suppressed serum cortisol levels in both the overnight and the low-dose dexamethasone suppression tests, indicating autonomous cortisol secretion and Cushing\'s syndrome. In a relatively short time, both patients developed night sweats, and their clinical picture deteriorated, while the CT scans showed increased dimensions of the masses with radiological characteristics compatible to lymphoma. Both patients underwent ultrasound-guided biopsies (FNBs), revealing infiltration of the left adrenal by diffuse large B-cell lymphoma in the first case, whereas bilateral adrenal infiltration from the same histological type was noted in the second case. Subsequently, they were treated with immunochemotherapy, but the second patient died from an infection shortly after the initiation of the treatment. To our knowledge, this is the first report of PAL presenting with Cushing\'s syndrome due to autonomous cortisol production, indicating that neoplastic lymphoid cells in PAL might acquire the potential for steroidogenesis; therefore, more cases of PAL should be analyzed so as to further elucidate the complex pathogenesis and the natural course of this entity.

The present study aimed to assess the existing data about Primary Adrenal Lymphoma (PAL) evaluated with FDG PET and to describe a small monocentric series of cases. A systematic analysis (from 2010 to 2022) was made by using PubMed and Web of Science databases reporting data about the role of FDG PET/CT in patients with suspicious or known adrenal lymphoma. The quality of the papers was assessed by using QUADAS-2 criteria. Moreover, from a single institutional collection between 2010 and 2021, data from patients affected by adrenal lymphoma and undergoing contrast-enhanced compute tomography (ceCT)/magnetic resonance (MR) and FDG PET/CT or PET/MR were retrieved and singularly described. Seventy-eight papers were available from PubMed and 25 from Web of Science. Forty-seven (Nr. 47) Patients were studied, most of them in the initial staging of disease (n = 42; 90%). Only in one paper, the scan was made before and after therapy. The selected clinical cases were relative to the initial staging of disease, the restaging, and the evaluation of response to therapy. PET/CT and PET/MR always showed a high FDG uptake in the primary adrenal lesions and in metastatic sites. Moreover, PET metrics, such as maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV), were elevated in all primary adrenal lesions. In conclusions, FDG PET either coupled with CT or MRI can be useful in staging, restaging, and for the evaluation of treatment response in patients affected by PAL.

Primary adrenal lymphoma (PAL) is an extremely rare entity, there were few cases have been reported. We report a 52-year-old female with unilateral PAL.
Case report.
A rapid biopsy resulted in the diagnosis of diffuse large B-cell lymphoma after excluding pheochromocytoma. R-CHOP combined with CNS prophylaxis and autologous stem cell transplant (ASCT) has produced an excellent outcome.
Primary adrenal lymphoma (PAL) is a sporadic and highly invasive malignant disease. Symptoms are atypical, making it difficult to obtain an accurate early diagnosis. Adrenal incidentaloma is usually the first clinical manifestation. Some patients may have fever, night sweats, weight loss, and lumbar and abdominal pain. Adrenal insufficiency (AI) may occur in a subset of patients. The identification of other adrenal malignancies, especially catecholamine-secreting tumors, is particularly important for early diagnosis.

Primary adrenal lymphoma (PAL) is an extremely rare malignancy, and it accounts for approximately 1% of non-Hodgkin\'s lymphoma (NHL). The growth of adrenal lymphoma is characterized by rapid infiltration in the adrenal gland and further involvement and metastasis in other tissues and organs. This report describes the case of a 67-year-old man with fatigue, poor appetite, and weight loss. Positron emission tomography and computed tomography (PET-CT) scan showed irregular mass-like soft tissue density shadows were noted in the bilateral adrenal glands and immunohistochemical (IHC) studies confirmed the diagnosis of PAL with multiple metastases throughout the body. This report characterizes the clinical manifestations in patients with PAL. When the disease progresses to bilateral adrenal involvement, it may be accompanied by adrenal insufficiency or even adrenal crisis occurred.

UNASSIGNED: Primary adrenal lymphoma (PAL) is an aggressive form of lymphoma associated with adrenal insufficiency (AI) in most cases. It requires a histologic confirmation unlike other cases of primary AI.
UNASSIGNED: We report a case of a 66-year-old man who presented with AI with symptomatic hypotension and hypo-osmolar hyponatremia. Ultrasound and computed tomography scans revealed bilateral bulky adrenal masses that were avid on fluorodeoxyglucose positron emission tomography scan. The diagnosis of PAL was confirmed with adrenal biopsy. He was treated with rituximab-based chemotherapy, which was complicated by several endocrine challenges, including worsening diabetes, multiple adrenal crises, prolonged hyponatremia, and refractory hypokalemia requiring spironolactone. He eventually developed central nervous system disease and was treated with palliative intent.
UNASSIGNED: AI in the setting of PAL can constitute both diagnostic and therapeutic challenges, including significant electrolyte imbalances as discussed in this case report.
UNASSIGNED: It is important to have a high suspicion for PAL, especially in the presence of bilateral adrenal masses and AI. Early adrenal biopsy is required for diagnosis. Multidisciplinary care is vital to manage complications that arise during the disease course and treatment.

Methotrexate-associated lymphoproliferative disorders (MTX-LPDs) with diffuse large B-cell lymphoma (DLBCL) pathology present with high rates of spontaneous regression after methotrexate (MTX) termination, especially in Epstein-Barr virus-encoded RNA (EBER)-positive cases. DLBCL with adrenal involvement is known for an extremely dismal prognosis. However, the prognosis of adrenal DLBCL in the context of MTX-LPD is unknown. We herein report two EBER-positive adrenal DLBCL MTX-LPD patients who achieved long-term remissions of 22 and 40 months with MTX termination alone. Both patients are doing well with no relapse at the time of reporting. Unlike adrenal DLBCL in general, adrenal involvement may not be a poor prognostic factor when restricted to DLBCL MTX-LPDs.

UNASSIGNED: Methotrexate-associated lymphoproliferative disorders appear during treatment with methotrexate as an immunosuppressive drug. However, the mechanism and frequency are still unknown, and the treatment is undefined.
UNASSIGNED: A 76-year-old woman was admitted to the hospital with back pain, and magnetic resonance imaging showed a tumor in the right adrenal region. She had received methotrexate for rheumatoid arthritis. Enhanced computed tomography showed a tumor of 90 mm in diameter on the dorsal side of the liver abutting to the inferior vena cava. The preoperative diagnosis was a hepatic invasion of right adrenocortical carcinoma and right adrenalectomy was performed. The histopathological diagnosis was diffuse large B-cell lymphoma. The final diagnosis was methotrexate-associated lymphoproliferative disorders.
UNASSIGNED: It is important to consider methotrexate-associated lymphoproliferative disorders before surgery when neoplastic lesions are found in patients taking methotrexate.

Primary adrenal lymphoma (PAL) is difficult to distinguish from other adrenal masses. Soluble interleukin-2 receptor (sIL-2R) is a diagnostic biomarker for nodal non-Hodgkin lymphoma, whose association with PAL is unknown.
The aim of this study was to determine the diagnostic utility of serum sIL-2R for Patients with PAL.
Prospective cohort study.
A total of 118 patients with adrenal masses who were willing to be tested for levels of serum sIL-2R from a tertiary hospital between 2019 and 2021 were included.
Serum sIL-2R and lactate dehydrogenase (LDH) levels.
Patients with PAL had significantly higher sIL-2R levels than those of patients with other adrenal masses with indetermined and benign computed tomography (CT) features (both Ps < 0.001). The LDH levels of patients with PAL were also significantly higher than those of patients with other adrenal masses with indeterminate and benign CT features (both Ps < 0.001). Good discrimination of patients with PAL from other patients (PAL vs other adrenal masses with indeterminate CT features/non-PAL) was achieved with an area under the receiver operating characteristic curve (AUC) of 0.984 (95% CI, 0.95-1)/0.992 (95% CI, 0.975-1.000) using the serum levels of sIL-2R and further improved (AUC = 0.998, 95% CI, 0.994-1.000; AUC = 0.999, 95% CI, 0.996-1.000) after adjusting by LDH category.
For the first time, we have identified that serum sIL-2R and LDH category-adjusted sIL-2R levels have good diagnostic performances for PAL.

Primary adrenal lymphoma (PAL) is a very rare type of non-Hodgkin\'s lymphoma (NHL). Herein, we report a case of NHL of both adrenal glands in a 69-year-old man. The patient was admitted because of a 1-month history of B symptoms and symptomatic hypotension. Biochemical analysis showed normocytic normochromic anaemia, hyponatraemia, hyperkalaemia, and elevated lactate dehydrogenase, C-reactive protein and D-dimers. A computed tomography scan revealed bilateral enlargement of the adrenal glands. There was no evidence of endocrine adrenal dysfunction. The mass in the right adrenal gland was biopsied and histopathology identified a diffuse large B-cell lymphoma of the activated B-cell subtype. A positron emission tomography 18F-fluorodeoxyglucose scan showed intensive hypermetabolic lesions involving both adrenal glands, as well as other locations, with higher uptake in the adrenal glands. Taken together, these findings suggested the diagnosis of PAL. The patient responded favourably to debulking therapy and is currently undergoing chemotherapy.
CONCLUSIONS: Primary adrenal lymphoma is a rare condition presenting with unspecific symptoms; diagnosis requires histopathological confirmation.Adrenal function must be evaluated to rule out insufficiency.Positron emission tomography may reveal hitherto unsuspected extension of disease and should be performed where available.

Primary adrenal lymphoma (PAL) is a rare form of adrenal mass. We summarize our experience in its clinical presentation, biochemical indexes, radiological features, pathological information, therapy regimens, and outcomes.
This was an institutional review board-approved retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of PAL at the Chinese People\'s Liberation Army General Hospital and the First Affiliate Hospital of Xiamen University between July 2007 and July 2017.
Twenty-six patients were identified. The mean age at presentation was 60.84 ± 13.14 years with a male-to-female ratio of 2.25:1 (18:8). The most common presenting symptoms were loss of appetite (65%, 17/26), weight loss (62%, 16/26), abdominal pain (58%, 15/26), and fatigue (58%, 15/26). The levels of lactate dehydrogenase (75%, 15/20), β2-microglobulin (100%, 10/10), C-reactive protein (82%, 14/17), and ferritin (88%, 7/8) and the erythrocyte sedimentation rate (83%, 10/12) were elevated. Bilateral involvement was seen in 21 of 26 patients (81%); 12 of 19 evaluated patients with bilateral lesions (63%) were confirmed to have adrenal insufficiency. On computed tomography (CT), the mean tumor diameter was 7.31 ± 3.35 cm and the median Hounsfield density was 37.0 HU (range: 31.0-45.0 HU); 67% (10/15) and 27% (4/15) of lesions presented with mild and moderate enhancement after injection of contrast medium. 18F-fluorodeoxyglucose positron emission tomography (FDG PET)-CT revealed not only an adrenal tumor but also extra-adrenal lesions. Diffuse large B-cell lymphoma (DLBCL) was the most common phenotype (92%, 24/26). Ninety-two percent (24/26) of patients received chemotherapy while 8% (2/26) received unilateral adrenalectomy plus chemotherapy. The prognosis of PAL was poor, with a general survival time of 7.20 ± 5.18 months.
PAL is a rare disease. The clinical characteristics of PAL include loss of appetite and weight loss. Endocrine evaluation should be performed to determine whether patients have adrenal insufficiency, especially patients with bilateral lesions. FDG-PET appears to be more accurate than other imaging modalities in revealing extra-adrenal sites. Better therapy is required to improve the poor prognosis of PAL.