A Novel Diagnostic Model for Primary Adrenal Lymphoma

ObjectivePrimary adrenal lymphoma (PAL) is easily misdiagnosed as other adrenal masses, such as adrenocortical carcinoma and pheochromocytoma, but patients with PAL benefit little from surgery. The diagnostic method for PAL thus far is limited to adrenal biopsy. In our study, we aimed to develop a quick and efficient diagnostic method for PAL.Methods and ResultsAt the same institution, 505 patients (between 2009 and 2019) and 171 patients (between 2019 and 2020) were separately included in the primary and validation studies. Univariate and multivariate analyses were conducted to evaluate clinical manifestations, laboratory findings, and radiological characteristics. Four determinants (age, bilateral masses, high-density lipoprotein cholesterol, and lactate dehydrogenase) were selected and further incorporated into a regression model to screen PAL. Accordingly, the nomogram was developed for clinical practice. In the primary study, the nomogram showed good discrimination, with an area under the receiver operating characteristic (ROC) curve (AUC) of 95.4% (95% CI, 90.6%–100.0%). Further validation study verified the efficacy of the nomogram, with an AUC of 99.0% (95% CI, 96.9%–100.00%) and 100.0% in all patients and patients with bilateral masses, respectively, and a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 66.67%/99.40%/66.67%/99.40%, 66.67%/100%/100%/92.86%, 50%/99.20%/50%/99.20%, and 100%/100%/100%/100%, in all patients, patients with bilateral adrenal masses, patients with nonfunctional adrenal masses, and patients with positive catecholamine results, respectively. The validation study also revealed a diagnostic specificity of 99.35% and 100% for patients with a unilateral adrenal mass and functional PCC, respectively.ConclusionsThe presented nomogram is the first user-friendly diagnostic model for PAL that simplifies the complex diagnostic process into personalized numeric estimates. We deem that patients who score below 50 are less likely to have PAL. We suggest that clinicians should arrange adrenal biopsy and surgery for patients with nonfunctional tumors and overt catecholamine-secreting tumors, respectively, who receive a score of 50 points or higher to confirm the diagnosis as soon as possible.

Download Full-text

SAT-185 Primary Adrenal Lymphoma Presenting with Symptomatic Hypercalcaemia

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1742 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Hannah Elizabeth Forde ◽

Jane Noble ◽

David Gibbons ◽

John Holian ◽

Connaghan Daniel Gerard ◽

...

Keyword(s):

Differential Diagnosis ◽

The Philippines ◽

Primary Adrenal Lymphoma ◽

Adrenal Biopsy ◽

Catecholamine Excess ◽

Positron Emission ◽

Adrenal Lymphoma ◽

Bilateral Adrenal Hyperplasia ◽

Synacthen Test ◽

Adrenal Masses

Abstract Introduction: Primary adrenal lymphoma (PAL) is a rare cause of adrenal enlargement with approximately 200 cases reported in the literature to date. It tends to affect elderly men and has a high incidence of bilateral involvement at diagnosis. We report the case of a 66 year old man, whose PAL manifested with symptomatic hypercalcaemia. A 66 year old male, originally from the Philippines, was referred to the emergency department with nausea, vomiting, weight loss and right flank pain. His past medical history was significant for hypertension, gout and stage 3b chronic kidney disease. His medications were amlodipine, losartan and febuxostat. His family history was significant for hypertension. On examination he was hypertensive (blood pressure, 160/100 mmHg) and hyperpigmented. His laboratory investigations revealed; corrected calcium of 3.79 mmol/l, undetectable PTH, vitamin D 49 nmol/l. He was treated with intravenous (IV) 0.9% saline and IV zoledronic acid and his calcium levels improved. To investigate causes of non-PTH mediated hypercalcaemia, computerised tomography of the thorax, abdomen and pelvis (CT TAP) as well as a positron emission tomography (PET) scan were performed. These demonstrated bilateral, large, metabolically active adrenal masses with no evidence of extra-adrenal disease. Differential diagnosis at this point included bilateral adrenal hyperplasia, metastases, lymphoma or adrenal TB. There were no radiological features of adrenocortical carcinoma (ACC) or phaeochromocytoma and subsequent biochemical investigations confirmed no evidence of cortisol, androgen or catecholamine excess. Adrenocorticotrophic hormone (ACTH) levels were elevated however, and a synacthen test revealed inadequate adrenal reserve (peak cortisol 214 nmol/l). The patient was commenced on maintenance steroids and with stress dose steroid cover, proceeded to adrenal biopsy. Histology confirmed diffuse large B cell non-Hodgkin’s lymphoma. Haematology became involved in his care and he commenced polychemotherapy in the form of R-CHOP, 1 week post confirmation of the diagnosis. His treatment is ongoing and he has tolerated it well with minimal side effects, except a flare of gout. Learning points: PAL should be considered in the differential diagnosis in patients with bilateral adrenal masses. Image guided adrenal biopsy is the gold standard for diagnosis, though caution must be exercised and an ACC or phaeochromocytoma should be excluded prior to biopsy. The prognosis of PAL is poor and therefore early diagnosis and prompt initiation of treatment are required to improve outcomes.

Download Full-text

Primary adrenal lymphoma: a case of hiccups

Oxford Medical Case Reports ◽

10.1093/omcr/omaa030 ◽

2020 ◽

Vol 2020 (4-5) ◽

Author(s):

Kylan Pathmanathan ◽

Venkata Kodali ◽

Abdulrazak Mohamad

Keyword(s):

Adrenal Insufficiency ◽

Adrenal Glands ◽

B Cell Lymphoma ◽

Primary Adrenal Insufficiency ◽

Primary Adrenal Lymphoma ◽

Adrenal Biopsy ◽

Large B Cell Lymphoma ◽

Adrenal Lymphoma ◽

Biochemical Evaluation ◽

Adrenal Masses

Abstract Approximately 250 cases of primary adrenal lymphoma have been reported. We describe an unusual presentation of this condition. Our patient is a 65-year-old male whom presented to the emergency department with 4 days of severe persistent hiccups. He had lost 26 kg in weight in the preceding 4 months. Computed tomography abdomen revealed large invasive bilateral adrenal masses. Biochemical evaluation confirmed adrenal insufficiency. Hiccups resolved within 24 h of steroid replacement. Adrenal biopsy confirmed a diffuse large B-cell lymphoma. Hypotheses for the aetiology of his hiccups include diaphragmatic irritation and primary adrenal insufficiency. This case is interesting for its rarity involving bilateral adrenal glands, Addison’s disease from the primary adrenal tumour and rapid resolution of hiccups with corticosteroid therapy.

Download Full-text

Tele-Oncology: A Validation Study of Choroidal and Iris Nevi

Ocular Oncology and Pathology ◽

10.1159/000494977 ◽

2018 ◽

Vol 5 (4) ◽

pp. 298-302 ◽

Cited By ~ 3

Author(s):

Kelsey Roelofs ◽

Ezekiel Weis

Keyword(s):

Positive Predictive Value ◽

Standardized Tests ◽

Clinical Examination ◽

Validation Study ◽

Predictive Value ◽

Primary Study ◽

Standard Testing ◽

Common Diagnosis ◽

Sensitivity Specificity ◽

Growth Methods

Background/Aims: To evaluate teleophthalmological assessment of choroidal and iris nevi (tele-oncology) compared to traditional in-person clinical evaluation for detection of either axial or basal growth. Methods: This is a validation study. All 97 eyes of 99 patients were evaluated with an in-person ocular oncology visit utilizing standard testing, and subsequently had a tele-oncology evaluation with the standardized tests. The tele-oncology reviewer was blinded to the in-person examination findings. The primary study outcome was detection of nevus growth on tele-oncology compared to in-person clinical examination. Results: Patients had a mean age of 61 years and the majority had nevi located in the choroid (n = 87; 88%). The most common diagnosis was a low-risk nevus (n = 38; 44%). By tele-oncology assessment, 11 eyes showed growth. Ten of these patients had growth confirmed on in-person clinical examination. Resultantly, tele-oncology assessment of choroidal and iris nevi growth had a sensitivity of 100%, specificity of 99%, positive predictive value (PPV) of 91%, and negative predictive value (NPV) of 100%. Conclusions: The results of this study suggest that tele-oncology is a safe platform for monitoring choroidal and iris nevi for growth, with excellent sensitivity, specificity, PPV, and NPV.

Download Full-text

Suspected Primary Adrenal Lymphoma (PAL) Associated With Hemophagocytic Lymphohistiocytosis (HLH)

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa156 ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Tara S Kim ◽

Kwan Cheng ◽

Radhika Jaiswal ◽

Pranisha Gautam-Goyal ◽

Alyson K Myers

Keyword(s):

Bone Marrow ◽

B Cell ◽

Bone Marrow Biopsy ◽

Hemophagocytic Lymphohistiocytosis ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Adrenal Incidentalomas ◽

Primary Adrenal Lymphoma ◽

Adrenal Lymphoma ◽

Adrenal Masses

Abstract Adrenal incidentalomas, masses noted on imaging performed for other purposes, are common, with 10% to 15% presenting as bilateral adrenal masses. These cases can be challenging as the differential diagnosis is broad, including metastatic disease, primary adrenal lymphoma (PAL), or infection, and often requiring a biopsy if initial biochemical workup is unrevealing. We present here a relevant case description, laboratory and radiologic imaging studies, and discussion of literature. A 62-year-old Korean woman presented with altered mental status and fevers. She was found to have bilateral adrenal incidentalomas and retained acupuncture needles. Adrenal workup did not show biochemical evidence of hormonal excess. Infectious workup was unrevealing, as was a metal/toxin workup due to retained acupuncture needles. Fevers and episodes of hypotension persisted which prevented the patient from obtaining an adrenal biopsy. Bone marrow biopsy was obtained for pancytopenia and revealed B-cell lymphoma with large cell morphology and few histiocytes with hemophagocytosis, raising concern for lymphoma-induced hemophagocytic lymphohistiocytosis (HLH). PAL associated with HLH was highly suspected in our patient, given the large (7 cm) bilateral adrenal masses and bone marrow biopsy findings of lymphoma. The patient was treated for diffuse large B-cell lymphoma, with clinical improvement. PAL is a rare but aggressive lymphoma with few reported cases. It should be considered in the differential for both unilateral and bilateral adrenal masses. An early diagnosis is crucial as the main treatment is chemotherapy rather than surgery and it confers a significant survival benefit.

Download Full-text

Primary Adrenal Lymphoma Presenting as Bilateral Adrenal Masses

The Endocrinologist ◽

10.1097/01.ten.0000206388.01581.a0 ◽

2006 ◽

Vol 16 (2) ◽

pp. 75-76 ◽

Cited By ~ 3

Author(s):

Umut Barbaros ◽

Ye??im Erbil ◽

Alp Bozbora ◽

U??ur Deveci ◽

Sel??uk ??zarma??an ◽

...

Keyword(s):

Primary Adrenal Lymphoma ◽

Adrenal Lymphoma ◽

Adrenal Masses

Download Full-text

Abstract #104: Primary Adrenal Lymphoma Presenting as Bilateral Adrenal Masses.

Endocrine Practice ◽

10.1016/s1530-891x(20)44165-5 ◽

2017 ◽

Vol 23 ◽

pp. 3

Author(s):

Adnan Haider ◽

James Burks ◽

Siddique Ayesha ◽

Ana Ramirez ◽

Chaar Natalia

Keyword(s):

Primary Adrenal Lymphoma ◽

Adrenal Lymphoma ◽

Adrenal Masses

Download Full-text

Primary adrenal lymphoma as a cause of adrenal insufficiency, a report of two cases

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-19-0131 ◽

2020 ◽

Vol 2020 ◽

Author(s):

Kaja Grønning ◽

Archana Sharma ◽

Maria Adele Mastroianni ◽

Bo Daniel Karlsson ◽

Eystein S Husebye ◽

...

Keyword(s):

B Cell ◽

Adrenal Insufficiency ◽

Cell Lymphoma ◽

Unknown Origin ◽

B Cell Lymphoma ◽

List Type ◽

Primary Adrenal Lymphoma ◽

Adrenal Lymphoma ◽

Adrenal Masses ◽

Learning Points

Summary Primary adrenal lymphoma (PAL) is a rare cause of adrenal insufficiency. More than 90% is of B-cell origin. The condition is bilateral in up to 75% of cases, with adrenal insufficiency in two of three patients. We report two cases of adrenal insufficiency presenting at the age of 70 and 79 years, respectively. Both patients had negative 21-hydroxylase antibodies with bilateral adrenal lesions on CT. Biopsy showed B-cell lymphoma. One of the patients experienced intermittent disease regression on replacement dosage of glucocorticoids. Learning points: Primary adrenal lymphoma (PAL) is a rare cause of adrenal insufficiency. Bilateral adrenal masses of unknown origin or in individuals with suspected extra-adrenal malignancy should be biopsied quickly when pheochromocytoma is excluded biochemically. Steroid treatment before biopsy may affect diagnosis. Adrenal insufficiency with negative 21-hydroxylase antibodies should be evaluated radiologically.

Download Full-text

SAT-187 Altered Mental Status in a Patient with Bilateral Adrenal Masses

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.781 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Sherin Elsa Mathews ◽

Jessica Castellanos-Diaz ◽

Alexis da Silva ◽

William Troy Donahoo ◽

Hans Kumar Ghayee ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Mental Status ◽

Clinical Case ◽

Flow Cytometric Analysis ◽

Altered Mental Status ◽

Primary Adrenal Lymphoma ◽

Uncommon Presentation ◽

Severe Hypercalcemia ◽

Adrenal Lymphoma ◽

Adrenal Masses

Abstract Introduction Primary adrenal lymphoma (PAL) is a very rare and aggressive form of Non-Hodgkin’s lymphoma originating from the adrenal glands and with no prior history of lymphoma. It can present with symptoms related to adrenal insufficiency due to tumoral destruction of normal adrenal tissue. Hypercalcemia has also been previously reported as a less common presentation of PAL. We describe here a case of PAL presenting with severe hypercalcemia and adrenal insufficiency. Clinical Case 75 year male presented with 50 pound weight loss, fatigue and anorexia for several months. On admission, patient had altered mental status. Further investigation revealed severe hypercalcemia (corrected calcium for albumin =15mg/dl) and AKI (serum creatine=3.45mg/dl, blood urea nitrogen=89). He was started on IV fluids for the hypercalcemia and AKI. Additional work up revealed suppressed parathyroid hormone (PTH) levels of 9 (12 - 88 pg/mL), high normal PTH-related peptide 22 (14-27), low 25-OHD 7.34 (20-120 ng/ml), high normal 1,25-(OH)2-D 63.0 (19.9-79 pg/mL). His ACTH level was elevated ~159 (7.2-63.3 pg/ml) with low normal morning cortisol levels ~10 mcg/dl. Patient was started on IV stress dose steroids for concerns of adrenal insufficiency and calcitonin was also initiated for the treatment of hypercalcemia. CT of the abdomen showed bilateral adrenal masses, measuring 9.8 x 6.4 x 10.8 cm on the right and 9.3 x 5.2 x 9.6 cm on the left with marked retroperitoneal lymphadenopathy. After ruling out pheochromocytoma with negative plasma and urine metanephrines, biopsy of the adrenal mass revealed a highly aggressive diffuse B large cell lymphoma, with BCL2 and MYC overexpression. Concurrent flow cytometric analysis also identified an abnormal population of medium to large B cells expressing bright CD20, CD19, CD38, CD45 without CD10, CD5, CD23 or overt kappa or lambda expression. His calcium levels improved with hydration and steroids. Chemotherapy was later initiated. Conclusion Primary adrenal lymphoma is rare and aggressive type of NHL. While adrenal insufficiency is expected in this clinical scenario, hypercalcemia from 1,25-(OH)2-D excess is a relatively uncommon presentation. Adrenal insufficiency should be ruled out in bilateral infiltrative adrenal masses. Likely etiologies for hypercalcemia in our case appeared to be secondary to elevated 1,25-(OH)2-D production, humoral hypercalcemia of malignancy and worsened by untreated clinically evident adrenal insufficiency. References (1) Laurent C, Casasnovas O, Martin L, et al. Adrenal lymphoma: presentation, management and prognosis. QJM. 2017 Feb 1;110(2):103-109. doi: 10.1093/qjmed/hcw174 (2) Masood A, Tumyan A, Nussenzveig D R., Wakefield D N., Barb D, Ghayee H K., Maalouf N M. The Diverse Clinical Presentations of Adrenal Lymphoma. AACE Clinical Case Reports: Autumn 2017, Vol. 3, No. 4, pp. e307-e312. doi: 10.4158/EP161595.CR

Download Full-text

Bilateral Adrenal Incidentalomas, Uncommon Presentation and Very Rare Pathology

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.239 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A119-A119

Author(s):

Mohammad Khair Ahmad Ibraheem Hamad ◽

Ahmed Osman Saleh ◽

Emad Naem

Keyword(s):

Ct Scan ◽

Adrenal Insufficiency ◽

Adrenal Mass ◽

Adrenal Glands ◽

Adrenal Incidentaloma ◽

B Cell Lymphoma ◽

Primary Adrenal Lymphoma ◽

Adrenal Lymphoma ◽

History Of ◽

Adrenal Masses

Abstract Background: Adrenal incidentaloma is an adrenal mass larger than 1cm accidentally discovered by radiological examination. The incidentalomas should be evaluated for malignancy and functionality. The prevalence of adrenal incidentaloma is 4–10%,1 and around 10–15% of incidentally discovered adrenal masses can be bilateral.2 We present a patient with bilateral adrenal masses due to primary adrenal lymphoma. Clinical Case: 74-year-old gentleman, with past medical history of type-2 Diabetes mellitus, hypertension, presented to our hospital with 2 months history of right-sided flank pain, 20 kg weight loss, loss of appetite and dizziness. Otherwise, no fever, night sweats, bleeding per rectum or urinary symptoms. On physical examination, vital signs were within normal, no remarkable findings other than tenderness over the right flank. Complete blood count and chemistry panel were within normal. Abdominal CT scan was done for evaluation of the abdominal pain which showed two large masses replacing the adrenal glands measure about 10cm in diameter with patchy areas of enhancement. Adrenal insufficiency was suspected based on the symptoms and the CT scan findings. Short syncatin test (high-dose test 250mcg) was done, which showed a cortisol baseline 152nmol/L, 30 minutes 168nmol/L, and 60 minutes 169nmol/L. This was suggestive of adrenal insufficiency, so he was started on hydrocortisone. Screening for pheochromocytoma was done as the patient developed uncontrolled BP readings prior to a scheduled adrenal biopsy. 24-hour urine metanephrines and normetanephrine were negative. CT-guided adrenal mass biopsy showed findings suggestive of large B-cell lymphoma. FDG PET-CT scan showed huge bilateral intense FDG uptake in the adrenal glands with no extra-abdominal manifestations noted. He was started on R-CHOP chemotherapy and after 4cycles, a PET scan showed a significant decrease in the size of previous adrenal masses. Conclusion: Bilateral adrenal incidentaloma should be evaluated the same as unilateral adrenal mass. Although adrenal involvement is common in non-Hodgkin lymphoma, primary adrenal lymphoma is extremely uncommon. References 1.Bovio S, Cataldi A, Reimondo G, Sperone P, Novello S, Berruti A, Borasio P, Fava C, Dogliotti L, Scagliotti GV, Angeli A, Terzolo M. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Invest. 2006 Apr;29(4):298–302. doi: 10.1007/BF03344099. PMID: 16699294. 2.Angeli A, Osella G, Alì A, Terzolo M. Adrenal incidentaloma: an overview of clinical and epidemiological data from the National Italian Study Group. Horm Res. 1997;47(4–6):279–83. doi: 10.1159/000185477. PMID: 9167965.

Download Full-text

Reliability and relationship of colposcopical, cytological and hystopathological findings in the diagnostic process

Vojnosanitetski pregled ◽

10.2298/vsp1210869m ◽

2012 ◽

Vol 69 (10) ◽

pp. 869-873 ◽

Cited By ~ 1

Author(s):

Vera Milenkovic ◽

Radmila Sparic ◽

Jelena Dotlic ◽

Lidija Tulic ◽

Ljiljana Mirkovic ◽

...

Keyword(s):

Predictive Value ◽

Diagnostic Method ◽

Diagnostic Methods ◽

Diagnostic Process ◽

Final Decision ◽

Gynecology And Obstetrics ◽

Clinical Center ◽

Negative Findings ◽

Malignant Changes ◽

Relationship Of

Background/Aim. The question about the accuracy of cytology and colposcopy is more and more asked due to false positive and negative findings on the basis of which the decision on biopsy is made. The aim of this study was to examine reliability of biopsies based only on abnormal colposcopical findings, before receiving the results of Papanicolaou (PA) smear, by comparing findings of colposcopical, cytological and histopathological (HP) examinations as well as determining validity of these diagnostic methods. Methods. The study involved all patients who had their regular colposcopical and cytological examinations in the outpatient department during a two-year period (2009-2010) in the Clinic for Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade. The material for HP examination was obtained by colposcopically directed biopsy, due to abnormal colposcopical findings and without waiting for PA smear results. The data obtained by these methods were statistically analyzed and compared. Furthermore, validity of colposcopical and cytological examinations was assessed. Results. Out of 127 patients highly significantly more patients had more malignant cervical changes on colposcopical exam compared to HP (p = 0.000), and cytological exam (p = 0.000). Highly significantly more patients had more malignant cervical changes on PA smear than HP exam (p = 0.000), unless when findings were assessed in the widest sense of benign and malignant changes when there were no significant differences in these findings (p = 0,450). Sensitivity of colposcopy as a diagnostic method was 87.5%, specificity 24.14%, positive predictive value (+PV) was 34.65% and negative predictive value (-PV) 80.77%. Sensitivity of PA smear as a diagnostic method was 62.5%, specificity 87.36%, +PV was 69.44%, and -PV 83.52%. Conclusion. Regarding the results of our study it is best to make a decision on treatment according to findings of all the three methods. Cytological analysis is more reliable than colposcopical examination. Therefore, it is advisable that following abnormal colposcopical findings, PA smear should always be taken and only after receiving the results further diagnostics can be planned (biopsy and HP). A final decision on the therapy has to be made based on HP findings which are the only method that can give the ultimate reliable diagnosis of cervical changes.

Download Full-text