American Journal of
Case Reports
| Received: | 2023.09.23 |
| Accepted: | 2023.12.11 |
| Available online: | 2023.12.21 |
| Published: | 2024.01.30 |
Uncovering Primary Extranodal Diffuse Large B Cell Lymphoma in the Adrenal and Thyroid Glands
Authors’ Contribution:
Study Design A
Data Collection B
BDE 2 Raisa Balbuena-Merle
Statistical Analysis C Data Interpretation D
BDE 3 Morgan Hrones
ADEF 1 Courtney Elizabeth Gibson
Manuscript Preparation E Literature Search F Funds Collection G
ABDEF 1 Judy Li İD
1 Section of Endocrine Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT USA
2 Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA
3 Department of Pathology, Yale School of Medicine, New Haven, CT, USA
| Corresponding Author: | Judy Li, e-mail: judy.li@yale.edu |
| Financial support: | None declared |
| Conflict of interest: | None declared |
Case series
Patients:
Female, 69-year-old . Female, 59-year-old
Final Diagnosis: Diffuse large B cell lymphoma
Symptoms: Abdominal pain . thyroid gland enlargement . hoarseness . dysphagia
Clinical Procedure:
Adrenalectomy . en bloc resection . nephrectomy . thyroidectomy
Specialty: Oncology . Surgery
Objective: Unusual clinical course
Background: Primary extranodal diffuse large B-cell lymphoma (DLBCL) is a rare, yet highly aggressive and invasive malig- nancy that can masquerade as a solid organ tumor. Timely diagnosis is critical for improving prognosis; how- ever, it is challenging to achieve.
Case Reports: We report 2 cases treated at Yale New Haven Hospital (New Haven, CT, USA) and the West Haven Veteran’s Affairs Medical Center (West Haven, CT, USA) in 2023. Case 1 describes a 69-year-old woman who presented with a large left adrenal mass that was suspicious for adrenocortical carcinoma and was found to have prima- ry adrenal DLBCL following surgical resection. Case 2 describes a 59-year-old woman with Hashimoto’s thy- roiditis and goiter who was found to have primary thyroid DLBCL following partial thyroidectomy. Conclusions: Primary extranodal DLBCL should be included in the differential diagnosis of solid adrenal and thyroid tumors. The risks of biopsy, given currently available techniques, should be weighed against the benefits of achieving a definite diagnosis, allowing for timely initiation of systemic immunochemotherapy. When biopsy can be safe- ly performed, techniques designed to evaluate for DLBCL should be incorporated.
Keywords: Adrenal Gland Neoplasms . Delayed Diagnosis . Lymphoma, Non-Hodgkin . Surgical Oncology . Thyroid Neoplasms
Full-text PDF: https://www.amjcaserep.com/abstract/index/idArt/942659
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Background
Diffuse large B-cell lymphoma (DLBCL) is an aggressive hemato- poietic malignancy that is diagnosed by its morphologic, immu- nophenotypic, and molecular profile. Patients most commonly present with a symptomatic lymphadenopathy, in which core or excisional lymph node biopsy is subsequently performed [1]. The average age of diagnosis is 64 years, and approximately 30% of patients experience B symptoms, which include fever, night sweats, and weight loss [2]. Roughly one-third of cas- es arise from extranodal sites (most commonly the gastroin- testinal tract or skin [3]); although, in cases where extranod- al and nodal disease coexist, it is challenging to differentiate between primary extranodal and nodal disease. The definition of primary extranodal DLBCL has remained controversial, but it is currently accepted to classify DLBCL as primary extranod- al when the extranodal component is clinically dominant and there is no to minimal nodal involvement or history of lympho- ma [4]. However, in rare cases, DLBCL can present as a solid organ tumor and masquerade as a carcinoma [5,6] or sarco- ma [7] on imaging, especially when symptoms are nonspecif- ic. Biopsies may thus not be routinely performed out of con- cern for malignancies in which tissue sampling prior to surgical resection is not indicated, such as in the first case described here of an adrenal mass suspicious for adrenocortical carci- noma. If biopsies are performed, such as in our second case, of an enlarging thyroid, standard techniques may not gather significant enough tissue or incorporate cytology techniques optimized for lymphoma detection, decreasing the likelihood of an accurate and timely diagnosis. The aim of this report is to share 2 cases of primary extranodal DLBCL presenting as solid organ tumors: the first being a case of primary adrenal DLBCL and the second being a case of primary thyroid DLBCL. Both cases presented with minimal lymphadenopathy in the absence of B symptoms and were not known to be DLBCL un- til after surgical resection.
Case Reports
Case 1
A 69-year-old woman presented to the Emergency Department with severe, worsening left upper quadrant and epigastric ab- dominal pain upon waking up that morning. The pain radiated to the left flank and pelvis. Her symptoms included intermit- tent hot flashes and nausea; she denied gastrointestinal symp- toms (vomiting, diarrhea, changes in appetite), B symptoms (fever, chills, night sweats), weight loss, chest pain, shortness of pain, or any genitourinary symptoms. She had been expe- riencing burning back pain for 8 months, which she controlled with over-the-counter pain medications, as well as nail ridg- ing and hair loss. She did not initially seek care, owing to lack
of insurance. However, she presented for care due to worsen- ing abdominal and flank pain that was no longer responsive to pain medications.
Computed tomography (CT) scan with contrast of the abdo- men and pelvis revealed a large (7.1×6.6×8.3 cm) left hetero- geneous, centrally hypodense and possibly necrotic mass in the left retroperitoneal space, with associated lymphadenopathy (eg, 2.2-cm left para-aortic lymph node). The mass appeared to be inseparable from the left kidney and adrenal gland and appeared to invade the left diaphragm (Figure 1). Follow-up CT scan of the chest and head did not reveal evidence of met- astatic disease or additional lymphadenopathy.
Magnetic resonance imaging (MRI) of the abdomen was addi- tionally performed and identified an enhancing mass favored to be of left adrenal origin. A normal left adrenal gland was not identified, and the mass and its associated retroperitone- al lymphadenopathy appeared to encase the left renal artery and vein and abut the aorta and the origin of the celiac and superior mesenteric arteries (Figure 2).
Surgical oncology, endocrine surgery, and urology services were consulted for initial workup. As reported in Table 1, blood test- ing revealed mild transaminitis and slightly low dehydroepi- androsterone sulfate. A negative dexamethasone suppression test and normal levels of thyroid stimulating hormone, adre- nocorticotropic hormone, plasma and 24-h urine epinephrine and metanephrines, aldosterone, and plasma renin activity suggested that the mass was likely non-functional.
Her past medical history was notable for hypertension and hy- pothyroidism, managed with losartan and levothyroxine, respec- tively. Her past surgical history included a hysterectomy and sal- pingo-oophorectomy, due to concern for possible cancer several years ago, but the final pathology report did not demonstrate any malignancy. She denied any family history of cancer and prior exposure to radiation; however, she was exposed to tox- ic chemicals while working as a housekeeper prior to retiring.
Given concern for locally advanced adrenocortical carcinoma, resection was planned and performed by a multidisciplinary team including endocrine, oncologic, thoracic, urological, and vascular surgeons. Out of concern for tumor seeding, a preop- erative diagnostic biopsy was not undertaken. The patient un- derwent an open left adrenalectomy with en-bloc nephrecto- my, para-aortic lymph node dissection, and partial diaphragm resection and repair. A large, firm multinodular mass involving the left adrenal gland, left upper pole of the kidney, left renal hilum, and diaphragm with para-aortic adenopathy was con- firmed intraoperatively. The mass encased the 2 left renal ar- teries and adhered to, but did not invade, the superior mes- enteric artery, celiac artery, and abdominal aorta.
A
B
70.8 mm (2D)
66.2 mm (2D)
83.0 mm (2D)
C
22.7 mm (2D)
A
80.5 mm
P
The en-bloc resection specimen (weighing 803 g and measuring 18×10×9 cm), including the kidney, adrenal gland, and a portion of diaphragm. A diagnosis of DLBCL, non-germinal center sub- type, was confirmed by morphologic evaluation and immuno- phenotypic analysis. The lesion, measuring 8.7×8.5×8.2 cm in size, consisted of a tan, bulky mass with a “fish-flesh” appear- ance (Figure 3). Microscopy and histopathological examination
of the mass revealed effacement of normal renal parenchyma by a diffuse proliferation of large lymphocytes with vesicular chromatin and variably prominent nucleoli. Increased mitot- ic activity with numerous apoptotic bodies and frank necrosis were also identified (Figure 4A). The tumor was cell CD20(+), CD10(-), CD30(-), CD138(-), MUM-1(+), BCL-2(+), BCL-6(+), and Ki-67(50%) (Figure 4B-4D). Central Nervous System International Prognostic Index score was 4. The fluorescence in situ hybridiza- tion (FISH) panel was negative for c-MYC gene rearrangements.
As reported in Table 2, HIV and hepatitis panels were nega- tive. Postoperative serum beta-2 microglobulin was elevated at 3.69 mg/L, and lactate dehydrogenase (LDH) was elevated at 309 in a slightly hemolyzed sample. The 18-fluorodeoxy- glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan demonstrated residual retroperitoneal metabolically active disease without splenomegaly. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy with intrathecal methotrexate and growth factor support were initiated.
Case 2
A 59-year-old woman with hypothyroidism secondary to Hashimoto thyroiditis presented with right neck swelling that
| Value (reference range) | |
|---|---|
| Complete blood count with differential | |
| White blood cell count | 5.4 (4.0-11.0×1000/uL) |
| Red blood cell count | 4.55 (4-6 M/uL) |
| Hemoglobin | 14.1 (11.7-15.5 g/dL) |
| Hematocrit | 42.60 (35.00-45.00%) |
| Mean corpuscular volume | 93.6 (80.0-100.0 fL) |
| Mean corpuscular hemoglobin | 31.0 (27.0-33.0 pg) |
| Mean corpuscular hemoglobin concentration | 33.1 (31.0-36.0 g/dL) |
| Red cell distribution width | 13.2 (11.0-15.0%) |
| Platelets | 267 (150-420×1000/µL) |
| Mean platelet volume | 11.4 (8.0-12.0 fL) |
| Neutrophils | 40.5 (39.0-71.0%) |
| Lymphocytes | 41.4 (17.0-50.0%) |
| Monocytes | 11.6 (4.0-12.0%) |
| Eosinophils | 5.8 (0.0-5.0%) |
| Basophils | 0.7 (0.0-1.4%) |
| Immature granulocytes | 0.0 (0.0-1.0%) |
| Nucleated red blood cells | 0.0 (0.0-1.0%) |
| Complete metabolic panel | |
| Sodium | 140 (136-144 mmol/L) |
| Potassium | 4.2 (3.3-5.3 mmol/L) |
| Chloride | 102 (98-107 mmol/L) |
| Blood urea nitrogen | 12 (8-23 mg/dL) |
seemed to subside following resolution of a viral infection, only to return and lead to compressive symptoms of voice hoarse- ness, morning cough, orthopnea, difficulty swallowing, and a positive Pemberton sign. She also developed predominant- ly left-sided neck tenderness. Other past medical history in- cluded hypertension, hyperlipidemia, gastroesophageal reflux disease, nephrolithiasis, and vitamin D deficiency. She had a right thyroid cyst drained 10 years ago but otherwise had no prior surgeries. She had no personal or family history of can- cer. A CT scan of the head and neck demonstrated a diffusely enlarged thyroid gland. A subsequent thyroid ultrasound re- vealed an enlarging left thyroid gland with left cervical lymph- adenopathy. The right thyroid lobe was 3.2×6.2×2.6 cm (vol- ume: 26.8 mL, increased from 20 mL 8 years ago), and the left thyroid lobe was 5.2×7.2×4.3 cm (volume: 83 mL, increased
| Value (reference range) | |
|---|---|
| Creatinine | 0.57 (0.40-1.30 mg/dL) |
| Alanine aminotransferase | 107 (10-35 U/L) |
| Alanine aminotransferase | 91 (10-35 U/L) |
| Alkaline phosphatase | 77 (9-122 U/L) |
| Total bilirubin | 0.4 (≤1.2 mg/dL) |
| Endocrine | |
| Thyroid stimulating hormone | 3.7 (0.27-4.20 ulU/mL) |
| Free cortisol, overnight dexamethasone suppression test | 1.4 (6.0-18.4 µg/dL) |
| Adrenocorticotropic hormone | 6.2 (7.2-63.3 pg/mL) |
| Norepinephrine | |
| Plasma | 459 (80-520 pg/mL) |
| 24-hour urine | 75 (15-100 mcg/24 h) |
| Metanephrines | |
| Plasma, free | <25 (<57 pg/mL) |
| 24-hour urine | 97 (21-153 mcg/g cr) |
| Dehydroepiandrosterone sulfate | 29.0 (35.0-430.0 µg/dL) |
| Plasma renin activity | 0.65 (0.25-5.82 ng/ml/h) |
| Aldosterone, morning | <1 (≤28 ng/dL) |
| Other | |
| Lipase | 25 (11-55 U/L) |
| Troponin, high sensitivity | Negative |
from 14 mL) with an enlarged cervical lymph node measuring 1.8×1.8×1.7 cm. Both lobes were heterogeneous, diffusely hy- poechoic without nodules and with hyperemic changes (mild on right; moderate on left).
Because of the patient’s extremely tender left neck and se- vere anxiety regarding biopsy of this area, as well as the lack of any discrete nodules within the gland, biopsy of the right thyroid lobe with fine needle aspiration (FNA) was performed. Cytologic evaluation revealed clusters of follicular cells with mixed lymphocytes, consistent with thyroiditis. As reported in Table 3, thyroid function test results were within normal lim- its, consistent with the known history of Hashimoto thyroid- itis and levothyroxine supplementation.
A
B
Q
A
B
C
D
| Value (reference range) | |
|---|---|
| Biochemical | |
| Lactate dehydrogenase | 309 (sample slightly hemolyzed) (122-241 U/L) |
| Beta-2 microglobulin | 3.69 (0.80-2.20 mg/L) |
| Infection screening | |
| Human immunodeficiency virus test | Negative |
| Hepatitis B surface antigen | Negative |
| Hepatitis C antibody | Negative |
A total thyroidectomy was planned for compressive symp- toms. During the operation, a large necrotic left thyroid lobe with extensive encasement of the trachea and carotid sheath structures was noted. Thus, a left partial thyroidectomy was completed for diagnostic purposes. Microscopy and histopath- ological examination of the resected specimen revealed a dif- fuse infiltrate of atypical cells. The cells were intermediate to large in size, with irregular nuclear contours and a scant to moderate amount of cytoplasm (Figure 5A). One section re- vealed intact foci of thyroid follicles without lymphoplasma- cytic infiltrates or lymphoepithelial lesions. The malignant cells were CD20(+), PAX-5(+), CD10(-), CD3(-), CD5(-), CD138(-), CYCLIN-D1(-), MUM-1(-), BCL-2(+), BCL-6(+), and Ki-67(80%) (Figure 5B-5D). Additionally, there was no light-chain restric- tion by immunohistochemistry. The morphologic and immuno- histochemistry features failed to rule in an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type or definite MALT transformation. The FISH pan- el was negative for BCL2 and BCL6 gene rearrangements but equivocal for c-MYC. This constellation of findings confirmed a diagnosis of DLBCL, germinal cell subtype.
Postoperative laboratory test results revealed elevated LDH but were otherwise noncontributory (Table 4). An 18F-FDG PET/CT scan demonstrated residual hypermetabolic activity in the re- maining thyroid gland and bed. Pola-R-CHP (polatuzumab ve- dotin, rituximab, cyclophosphamide, doxorubicin, and pred- nisone) therapy was initiated with prophylactic allopurinol, trimethoprim-sulfamethoxazole, and valacyclovir.
Discussion
Primary adrenal DLBCL and primary thyroid DLBCL are extreme- ly rare malignancies, each accounting for less than 2% to 3% of all primary extranodal lymphomas [8,9]. Both DLBCL cases
| Value (reference range) | |
|---|---|
| Thyroid | |
| Thyroid stimulating hormone | 2.94 (0.5-5.0 mIU/L) |
| Free thyroxine | 1.1 (0.9-2.3 ng/dL) |
| Thyroid peroxidase antibodies | 35 (<34 IU/mL) |
| Antithyroglobulin | 59 (<116 IU/mL) |
described in this report presented as symptomatic, enlarging non-functional solid organ tumors with minimal associated lymphadenopathy and without B symptoms. Diagnosis of DLBCL was not reached until after surgical resection was performed.
In case 1, preoperative biopsy was not conducted due to con- cern for adrenocortical carcinoma. Current guidelines recom- mend against biopsy of large adrenal masses suspicious for malignancy, such as adrenocortical carcinoma, given inevitable resection in most cases, limited diagnostic utility, and risks for complications and needle-track seeding [10,11]. The exception to this rule is when an adrenal mass requires a treatment oth- er than surgical resection, such as in the case of lymphoma re- quiring immunochemotherapy. In practice, this distinction be- tween adrenocortical carcinoma and DLBCL can be extremely challenging to discern with confidence, given the heterogene- ity of presentation. Preoperative biopsy of adrenal masses has been generally avoided because of the aforementioned risks; however, recent advances in image-guided techniques have im- proved biopsy safety without compromising tissue quality [12,13] and may have the potential to change guidelines in the future.
In contrast, preoperative FNA remains the universal criteri- on standard first-line diagnostic tool for thyroid malignan- cies and thus was performed in case 2. However, FNA failed to reveal DLBCL and only demonstrated Hashimoto disease. Resection was ultimately performed for compressive symp- toms, and only then was DLBCL revealed on tissue patholo- gy. Thyroid FNA appears to have decent diagnostic accuracy in detecting malignancy, with sensitivities ranging from 65% to 98% and specificities from 72% to 100% [14]. Unfortunately, diagnostic performance of FNA is markedly poorer in cases of lymphoma due to limited tissue sampling [15,16], and thus, more generous core, if not excisional, biopsies are recommend- ed over FNA when lymphoma of the thyroid is suspected [16]. Different cytology tests also have varying degrees of sensitiv- ity for detecting atypical cells. In practice, cell block prepara- tions are selected based on clinical impression, which in this case was goiter without nodules and Hashimoto thyroiditis, and thus a cell block preparation not designed for the evalu- ation of lymphoma (ie, one with significant artifact and low
A
B
C
D
cellularity) was used. Finally, the FNA was performed on the less tender and less diseased side of the thyroid, which may have further reduced the likelihood of lymphoma detection.
Consideration of DLBCL is important in the evaluation of all sol- id organ tumors because DLBCL must be treated with system- ic immunochemotherapy as opposed to solely surgical resec- tion. Assessment of DLBCL likelihood in such tumors can help weigh the risks and benefits of preoperative biopsy, which is required for definitive diagnosis, but is challenging. In the ab- sence of systemic B symptoms, which is the case among the vast majority of patients presenting with DLBCL, the clinical presentation of DLBCL can be especially difficult to differentiate from those of other malignancies. Common local symptoms of primary adrenal or primary thyroid lymphoma (eg, abdominal
pain and symptomatic goiter, respectively) are highly nonspe- cific. Elevated LDH could reflect DLBCL but is also nonspecific and does not rule out other disease processes [17]. Elevated serum beta-2 microglobulin and atypical cells on peripheral smears could similarly increase suspicion for a lymphoprolifer- ative disorder such as DLBCL; however, they are currently not routinely ordered in the workup of solid organ tumors (and were not ordered in either of these cases prior to diagnosis).
However, as more cases of primary adrenal and primary thy- roid DLBCL are reported and studied, patterns may emerge and help guide diagnostic workup. The largest systematic review of primary adrenal lymphoma to date, consisting of 187 cases, found that most cases were among elderly men (with a 1.8: 1 male-to-female ratio), involved bilateral adrenal glands (75%),
| Value (reference range) | |
|---|---|
| Biochemical | |
| Lactate dehydrogenase | 280 (125-243 U/L) |
| Complete blood count with differential | |
| White blood cell count | 4.3 (4.5-11.0×1000/µL) |
| Red blood cell count | 3.65 (3.93-5.16 M/uL) |
| Hemoglobin | 11.9 (12-15.2 g/dL) |
| Hematocrit | 36.0 (36.60-45.60%) |
| Mean corpuscular volume | 99.0 (82.0-99.0 fL) |
| Mean corpuscular hemoglobin | 32.6 (26.2-32.6 pg) |
| Mean corpuscular hemoglobin concentration | 33.1 (30.8-35.1 g/dL) |
| Red cell distribution width | 14.0 (12.0-16.0%) |
| Platelets | 234 (140-360×1000/µL) |
| Mean platelet volume | 11.1 (9.2-12.4 fL) |
| Granulocytes | 55.0 (43.7-75.8%) |
| Lymphocytes | 29.3 (14.0-42.3%) |
| Monocytes | 9.8 (5.1-13.7%) |
| Eosinophils | 0.0 (0.4-6.8%) |
| Basophils | 1.9 (0.1-2.0%) |
| Nucleated red blood cells | 0.7 (0.0%) |
| Basic metabolic panel | |
| Serum sodium | 140 (135-145 mmol/L) |
| Serum potassium | 4.3 (3.5-5.0 mmol/L) |
| Serum sodium | 104 (100-108 mmol/L) |
| Blood urea nitrogen | 13 (7-25 mg/dL) |
| Creatinine | 0.74 (0.50-1.50 mg/dL) |
and presented with adrenal insufficiency (61%) and elevated LDH (88%) [18]. More recent studies of case series have yield- ed similar findings [19-21], although the largest series of 97 patients found the distribution between bilateral and unilat- eral adrenal involvement to be more evenly split [21]. Despite these emerging associations, the clinical spectrum of prima- ry adrenal lymphoma appears vast, and current retrospective studies have been limited by heterogeneity in the data col- lected and reported. On the other hand, primary thyroid lym- phomas appear to have a greater predominance in elderly women (with a 3: 1 female-to-male ratio [22]). In addition,
Hashimoto thyroiditis has been associated with an estimated 60-fold increase in risk for thyroid lymphoma [16,23], although it is more commonly associated with papillary thyroid carcino- ma [24]. Interestingly, calcifications have been a common find- ing on ultrasound and CT imaging in thyroid carcinoma [25] but uncommon in thyroid lymphoma [26]. Overall, these asso- ciations alone remain inadequate in discriminating lymphoma from other pathologies without biopsy. Further work can be directed toward identifying profiles of risk factors and clini- cal attributes that may increase suspicion for lymphoma and therefore inform decision-making, namely, whether or not to perform a biopsy in light of risks associated with comorbidi- ties and other diseases on the differential, amount of tissue to biopsy, cell block preparation methods.
The cases described in this report were consistent with the proposed classic presentation of primary thyroid lympho- ma but not that of primary adrenal lymphoma, which is un- surprising given the greater clinical heterogeneity of the lat- ter disease. Surgical resection was most likely inevitable due to mass effect symptoms. Given that the resected tissue pa- thology would yield a definitive diagnosis, efforts could be di- rected toward expediting an excisional tumor biopsy when lymphoma is suspected and if surgery is to be inevitably per- formed for symptom management. However, if not expedit- ed, postponement of surgery can delay diagnosis and initia- tion of necessary chemotherapy. Prior studies have also failed to identify any survival benefit from surgical resection in pri- mary adrenal [19] and primary thyroid DLBCL [9], unless sup- plemented with systemic chemoimmunotherapy (eg, R-CHOP or pola-R-CHP) at early stages [27]. Thus, the impact of a po- tential delay in diagnosis and treatment in the absence of a preoperative biopsy should be carefully considered if surgi- cal resection is pursued. In the case of smaller or asymptom- atic masses not requiring immediate resection for symptom- atic relief, a preoperative biopsy can be beneficial if it can be performed safely. Current guidelines for DLBCL diagnosis rec- ommend an excisional lymph node biopsy over core biopsy or FNA, which are more susceptible to false negatives or incon- clusive results due to limited sampling [1,28]. However, when primary extranodal disease is being considered, lymph nodes may or may not be involved, and thus, lymph node biopsy can be required. Benefits and risks of the procedure differs based on disease burden, safety of biopsy given the target tissue and available techniques, tissue sample quantity and quali- ty, timing of potential resection, and the types of malignan- cies being considered.
Conclusions
As discussed in this brief 2-case series, primary adrenal DLBCL and primary thyroid DLBCL are rare yet aggressive
hematopoietic malignancies that require histopathology re- view for diagnosis. Given clinical presentations that overlap with solid organ tumors suggestive of other malignancies, such as thyroid carcinoma and adrenocortical carcinoma, bi- opsies with a large enough sample and sensitive cytology tech- niques may not be performed prior to surgical resection, lead- ing to delays in diagnosis and initiation of necessary systemic immunochemotherapy.
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Declaration of Figures’ Authenticity
All figures submitted have been created by the authors who confirm that the images are original with no duplication and have not been previously published in whole or in part.
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