We report a rare case of unilateral primary adrenal lymphoma. The patient was a 52-year-old female presenting with lumbar pain and weight loss as the initial symptoms; she had no symptoms of cortical insufficiency, such as pigmentation or fatigue. Clinical tests showed increased LDH and C-reactive protein (CRP) levels, yet her PTC was normal. The clinical and imaging features of this patient were consistent with those of reported PAL cases[5, 13].
PAL is a rapidly progressing malignant lymphoma. It has been previously reported that patients often die during treatment [6, 14–16]. We also reported a case of very rapid progression to death during hospitalization while waiting for a pathological diagnosis [17]; hence, early detection and diagnosis of suspected PAL is indispensable. However, the clinical manifestations of PAL lack specificity because most are nonfunctional tumors, which makes early diagnosis of PAL extremely difficult..
Several previous studies have found that PAL is more common in men over 60 years old (74.26%)[11, 18], usually presenting as unilateral adrenal incidentaloma without any symptoms. Adrenocortical insufficiency is rare, but if present, it is more common in patients with bilateral adrenal lesions (50%-70%) [2, 14, 19, 20].
Overall, unilateral adrenal PAL is more likely to be accompanied by type B symptoms, of which abdominal pain is the predominant symptom [21], and adrenal insufficiency is rare[8]. Our previous retrospective analysis of 50 PAL patients in our hospital found that the most common initial symptoms of PAL were lumbago and abdominal pain (48.9%), adrenal incidentaloma (28.9%), and B symptoms (27.7%). Therefore, PAL should be highly suspected for patients with adrenal incidentaloma if accompanied by lumbar and abdominal pain and B symptoms. In addition, CT is very important. Primary adrenal lymphomas are typically metabolically hyperactive, hypovascular tumors that present on CT scans with slight-to-moderate enhancement[22]. The adrenal cortex and medulla should be urgently evaluated, and biopsy should be arranged after excluding the possibility of a catecholamine secreting tumor[17].Here, we emphasize that when adrenal lymphoma is suspected, the application of core needle biopsy should be specifically applied for biopsy, and flow cytometry of the tissue homogenate should be conducted by the Pathology Department in a timely manner, which will be of great help for diagnosis.
Some biochemical indicators can help us identify cases of PAL. A few studies have found that an increase in LDH and a decrease in HDL-C are common in PAL patients [1, 8, 23, 24]. We also previously found significantly elevated LDH and decreased HDL in 50 patients[5]. In another study from our center[25], we established a cohort to evaluate the specificity of the above clinical markers in differentiating PAL and other adrenal malignancies, showing that age, single/bilateral lesions, HDL-C level, and LDH level are significantly associated with PAL. Furthermore, age (OR, 1.07, 95% CI, 1.02–1.14), bilateral masses (OR, 7.37, 95% CI, 1.44–39.29), HDL-C (OR, 0.12 95% CI, 0.01–0.68), and LDH (OR, 1.01, 95% CI, 1.01–1.02) have been verified as independent determinants of PAL. Each indicator corresponds to a score in this model; patients who score over 50 points have a greater than 90% possibility of having PAL. This prediction model can help with rapid, early diagnosis of PAL [25]. Nonetheless, the incidence of PAL is very low, and sample sizes in studies on PAL are small. Therefore, more research is needed to further explore how to diagnose these patients early and provide treatment in a timely manner.
The patient in this case reported back pain and weight loss, and imaging examination revealed a unilateral adrenal incidentaloma without other specific symptoms. According to clinical evaluation, the patient’s adrenal function was normal, but her LDH was increased and her HDL decreased. Based on our comprehensive nomogram scoring system comprising age, single/bilateral lesions, HDL-C level, and LDH level[25], the scores of each key index were as follows: age 52 years old (11 points), unilateral lesions (0 points), LDH 759 IU/L (24 points), and HDL-C 0.92 mmol/l (20 points). Thus, the total score of the nomogram evaluation was 55 points (higher than 50), and PAL was the first highly suspected diagnosis to be considered. After excluding pheochromocytoma, we arranged a core needle biopsy of the adrenal mass as soon as possible and repeatedly communicated with the Pathology Department to speed up the subsequent examination. The final diagnosis was DLBCL in the adrenal gland.
Treatment of PAL includes surgery, combined chemotherapy, postoperative chemotherapy and/or radiotherapy, and replacement therapy with corticosteroids. Several studies have reported a significant difference in survival time between patients receiving chemotherapy and those receiving conservative treatment. CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) combined with chemotherapy is the first choice for treating PAL [1, 5, 8]. In some cases, a non-CHOP regimen has been used, achieving a good prognosis [26]. In some cases, a non-CHOP regimen has been used, achieving a good prognosis[26]. Rituximab (R) binds to transmembrane antigen CD20 and initiates the immune response mediated by B cell lysis. Therefore, rituximab is recommended as targeted treatment for CD20-positive immunohistochemical results[27]. The complete remission (CR) rate of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) is 54.8%, the overall remission (OR) rate is 87.0%, and the 2-year overall survival (OS) and progression-free survival (PFS) rates are 68% and 51%, respectively[28]. Surgical treatment or laparoscopic adrenalectomy is not recommended as adjuvant treatment due to the high risk of recurrence and because surgery does not improve the survival rate of patients [28, 29]. As PAL itself is a rare tumor, research with a larger sample or a case analysis are needed to verify the above results.
The need for central nervous system prophylaxis, given reports raising the possibility of a high risk of parenchymal or meningeal relapse[30, 31]. Based on the international prognostic index score (a standard prognostic tool for patients with DLBCL), central nervous system involvement is a poor prognostic factor [32].Therefore, central prophylaxis in these patients must be integrated into the overall treatment plan. This patient's histochemistry showed C-MYC (+) and BLC-2 (+), which was the basis for the diagnosis of double-expressor DLBCL; we added sidabenamine because of the dual-expressed lymphoma. The addition of sidabenamine to dual-expressing lymphoma is known as CR-CHOP, and is currently being explored by hematologists as a treatment strategy for this high-risk group of DLBCL [33]. R-CHOP chemotherapy and preventive intrathecal chemotherapy can be combined to achieve a better prognosis [1, 5]. S Studies have shown 5-year overall and progression-free survival rates of 56.5% and 57.5%, respectively, when R-CHOP is combined with prophylactic intrathecal chemotherapy [26]. Studies have shown 5-year overall and progression-free survival rates of 56.5% and 57.5%, respectively, when R-CHOP is combined with prophylactic intrathecal chemotherapy [8, 13, 28]. The successful experience regarding the current case was that we added cedarbenamide according to the pathological subtype and actively performed autologous hematopoietic stem cell transplantation.
Based on the above research results, the patient received R-CHOP supplemented with preventive intrathecal chemotherapy during the middle of the chemotherapy sessions and hematopoietic stem cell transplantation after the completion of all chemotherapy and consolidation treatment sessions. After discharge, the patient had regular close follow-up at the Hematology and Endocrinology departments. Regular evaluation of the response to chemotherapy and dynamic monitoring of various indexes, including adrenocortical function, indicated that the patient did not have adrenal insufficiency since the beginning of treatment. All follow-up indexes indicated a good prognosis. The patient’s LDH decreased significantly to 143 IU/L, and her HDL-C and blood glucose, routine blood indexes, liver function, renal function, adrenocortical function and electrolytes returned to normal ranges. This case illustrates that this regimen can effectively alleviate PAL and improve prognosis.
In general, PAL prognosis is related to multiple risk factors. Older age, bilateral lesions, adrenal insufficiency, B cell symptoms, elevated LDH, central nervous system recurrence, and non-GCB type are predictors of poor prognosis[11, 34]. Several studies have shown that the LDH level is not only an important prognostic factor but can also predict survival [1, 8, 23, 32], and elevated serum LDH levels are associated with worse outcomes [21]. Early identification and biopsy and the treatment scheme of R-CHOP combined with autologous stem cell transplantation are essential for better therapeutic outcomes.