Residual Tumor Research Articles

12526 Acromegaly Secondary to Sparsely Granulated Adenoma

Abstract Disclosure: D. John: None. M. Kinaan: None. J. Titus: None. K. Lamar: None. The most common pathological finding in acromegaly is a densely granulated adenoma which is composed of large round eosinophilic cells with prominent nucleoli and spherical nuclei that closely resemble a somatotroph cell. Less common finding is a sparsely granulated adenoma that is composed of sheets of poorly cohesive, pleiomorphic nuclei, chromophobic cells. We present a case of a 58-year-old gentleman presenting to our endocrine clinic for evaluation of a pituitary macroadenoma. The patient was hospitalized for nausea, vertigo, headaches, and blurring of vision. CT brain at that time showed a pituitary mass measuring 2.4 x 1.6 x 1.7 cm centered in the right cavernous sinus and inseparable from the pituitary gland. Hormonal work-up in the hospital was remarkable for high GH level. IGF-1 level was not done. Patient was advised to follow-up with neurosurgery as outpatient and no emergent surgery was planned. In the clinic, patient denied symptoms of DI, adrenal insufficiency or hypothyroidism. He has history of hypogonadotropic hypogonadism and was on testosterone therapy, but he stopped it since his hospitalization. On physical examination, he was noted to have macroglossia, deep voice, prominent jawbone, and soft tissue swelling in the hands and feet. Patient did not have any visible joint swelling. He stated he did not notice these changes personally and that he’s always been a “big guy” and always had a deep voice since he was a teenager. Repeat hormonal workup (done at 8 AM) showed: normal CMP, ACTH, cortisol, prolactin, TSH, T4, and T3. Testosterone was low with LH and FSH inappropriately within the normal reference range consistent withhypogonadotropic hypogonadism. IGF-I was elevated at 628ng/mL with a Z score of 3.9. These findings were consistent with acromegaly. He underwent surgery for tumor resection and pathology report showed that about 40% of the cells demonstrated weak immunoreactivity for GH, and rare (less than 1%) prolactin-positive cells were present within the tumor. The specimen was negative for TSH, ACTH, FH, and LH immunostains. Immunostain for CAM5.2 showed predominantly perinuclear dot-like immunoreactivity. The *MIB1 proliferation index is about 1%. The findings were consistent with a sparsely granulated gonadotrophic adenoma, which may demonstrate aggressive behavior. Postoperative MRI showed postoperative changes with residual pituitary tissue (normal gland vs. residual tumor). Postoperative cortisol >16. Postoperative GH dropped from 4.39 to 2.69 after 1 month. After 3 months, patient was doing well with no symptoms. However, IGF1 level (>400) showing that surgery was not curative. Currently he is awaiting gamma knife radiation therapy with possible medical therapy afterwards. Our case will provide an overview of the specific management considerations for these tumor and how they differ from densely-granulated tumors. Presentation: 6/3/2024

12612 Chiasmal Herniation - A Rare Complication Of Prolactinoma Treatment

Abstract Disclosure: A. Syeda: None. V. Kantorovich: None. Introduction: Primary treatment of symptomatic prolactinomas is medical therapy with dopamine agonists (DA). Herniation of optic chiasm is a rare complication of tumor shrinkage induced by DA therapy which causes secondary deterioration in visual fields. Case:A 26-year-old man presented to our hospital after a syncopal episode. He had headaches and blurry vision in the left eye for the past 4 months. He was diagnosed with a 4 cm x 3.6 cm x 2.6 cm pituitary macroprolactinoma compressing the optic chiasm, his prolactin (PRL) was 4700 ng/mL (N: 4.0-15.2 ng/mL) and testosterone was suppressed to 10 ng/dL (N: 249-836 ng/dL). Other hormonal workup was unremarkable. Ophthalmologic evaluation was consistent with left optic nerve pallor and neural rim thinning suggestive of a guarded prognosis. Immediate neurosurgical intervention was deemed unnecessary. Cabergoline 0.25 mg twice a week was initiated. Subsequently, the PRL levels improved but remained elevated to 414.2 ng/mL and cabergoline dose was increased to 0.5 mg twice a week. MRI Brain after 10 months revealed significant tumor reduction to 2.1 cm x 2.1cm x 1.2 cm. He was inconsistent with his endocrinology follow up appointments and was also non-adherent to cabergoline intermittently. After 14 months of starting DA therapy, he presented with worsening blurriness in his left eye. A repeat brain MRI showed stable appearance of the large pituitary macroadenoma with inferior bowing of the optic chiasm. Significant distortion, tented appearance, and attenuation of the left prechiasmatic optic nerve was also noted. He was evaluated by neuro ophthalmology and a diagnosis of secondary visual deterioration due to optic chiasmal herniation was made. Cabergoline therapy was promptly discontinued. Two weeks post-cabergoline cessation, he underwent trans-sphenoidal resection reporting vision improvement pre-surgery. Post-operative MRI depicted changes with no residual tumor and improved optic chiasm position. Discussion:Various theories explain chiasmal herniation with dopamine agonist (DA) treatment for prolactinomas. Pre-existing chiasm-tumor tethering may exacerbate downward pull during tumor reduction caused by DA therapy. Some case series have suggested that not all patients with chiasmal herniation have visual field defects and that despite improvement in visual fields with decrease in DA dosage, there are no appreciable radiographic changes/reversal of chiasmal herniation. One of the explanations for this lack of correlation is that visual impairment is rather a consequence of vascular compression. This case underscores the need for regular perimetry in macroprolactinoma patients on medical treatment. Adjusting dopamine agonist dosage to allow controlled tumor regrowth, monitored closely with frequent visual field and prolactin assessments, is crucial for relieving optic chiasm tension. Presentation: 6/3/2024

7777 The Adrenal Tumor Volumes Help Predict Surgical Indications And Postoperative Recurrence Of PMAH

Abstract Disclosure: S. Suzuki: None. K. Ishiwata: None. Y. Ruike: None. K. Igarashi: None. S. Watanabe: None. M. Sugo: None. M. Fujimoto: None. H. Koide: None. K. Yokote: None. Introduction: Primary macronodular adrenal hyperplasia (PMAH) is characterized by benign bilateral enlarged adrenal masses, causing Cushing's syndrome (CS). Unilateral adrenalectomy of the largest gland has been proposed as a treatment for PMAH. However, there are cases of recurrence or persistence of hypercortisolism after unilateral adrenalectomy, and remaining tumor volumes might be associated. Objective: This study aimed to analyze whether tumor volume helps select treatment and predict postoperative recurrence. Patients and methods: We conducted a retrospective study of thirteen patients (five males and eight females, mean age 59 years) with CS due to PMAH in a single center. Eight patients with PMAH underwent unilateral adrenalectomy, but five PMAH were not. Long-term clinical and biochemical outcomes were analyzed in operated and non-operated patients (112±57 months after unilateral adrenalectomy and 144±49 months after initial diagnosis, respectively). Results: Eight PMAH patients who underwent unilateral adrenalectomy had total tumor volumes greater than 1500 mm2. After unilateral adrenalectomy, when the size of the remaining adrenal tumor was greater than 1000 mm2 (1053, 1268, and 1910, respectively), recurrence occurred along with enlargement of the residual adrenal tumor in two cases, and diabetes worsened in one case. However, when the size of the remaining adrenal tumor was less than 500 mm2 (18.2, 201, 214, 327, and 446, respectively), CS resolved. Among five PMAH patients who did not receive surgery, three PMAH patients with total tumor volume less than 1500 mm2 (856, 1038, and 1496, respectively) were biochemically controlled. However, in two PMAH patients with a total volume greater than 1500 mm2 (1610 and 1650), Cushing's signs, including buffalo hump and central obesity, appeared and worsened metabolic complications during follow-up. Conclusions: Our data suggest that adrenalectomy should be considered in PMAH with a total tumor volume greater than 1500 mm2. Unilateral adrenalectomy might have a risk of recurrence if the remaining adrenal tumor is over 1000 mm2. Further large-scale examination is required. Presentation: 6/3/2024

6400 An Unusual Presentation of Silent Corticotroph Pituitary Macroadenoma

Abstract Disclosure: N. Mon: None. V. Lohano: None. B. Williams: None. N. Lehman: None. R. Kulkarni: None. S.L. Mokshagundam: None. Silent Corticotroph Pituitary Adenomas (SCA) are a rare group of nonfunctioning pituitary adenomas (NFA) comprising 3-6% of all pituitary adenomas and up to 20% of corticotroph adenomas. SCA are biologically and clinically distinct from Cushing disease and NFA. SCA present with headache, visual field impairment, hypopituitarism, and pituitary apoplexy. We present a case of SCA with the initial presentation of syncope with undetectable ACTH and very low AM cortisol level.A 67 year-old-female was incidentally found to have a pituitary macroadenoma in MRI brain for syncope work up in 2017. MRI reported 1.4 x 1.2 x 1.3 cm sellar mass with suprasellar extension, minimal mass effect on the optic chiasm and no cavernous sinus invasion. Initial labs showed ACTH <5 (7.2-63.3 pg/mL), AM cortisol 0.8 (6-28ug/dl), Prolactin 101.1 (3.3-27 ng/mL), TSH 0.08 (0.34-5.60 uIU/mL), Free T4 0.6 (0.58-1.64 ng/dL), FSH 1.7 (2-5 mIU/mL), LH <0.2 (1-13 mIU/mL), IGF-1 33 ( 41-279 ng/mL). ACTH stimulation test: cortisol 0.5 ug/dl at baseline, 5.8 ug/dl at 60min. She was diagnosed with panhypopituitarism and hyperprolactinemia due to stalk effect. Hydrocortisone and Levothyroxine (LT4) were started. She underwent pituitary macroadenoma resection for optic chiasm decompression in 2017. Pathology reported pituitary neuroendocrine tumor (pitNET), but no immunostaining was done at that time. Follow up MRI in 2019 showed residual pituitary tumor. In 2023, she endorsed headaches, mood changes, fatigue and weight gain. Physical exam was unremarkable except BMI 34.75. Prolactin, Free T4, IGF-1 were normal. MRI in 2023 revealed recurrent and enlarging pituitary adenoma (1.9 x 1.4 x 1.6 cm) with suprasellar extension, abutting the optic chiasm, and left cavernous sinus invasion with internal carotid artery encasement. She underwent revision transsphenoidal resection of pituitary tumor to decompress the optic chiasm with plan for subsequent focused radiation to the cavernous sinus portion. Postoperative period was uneventful and hydrocortisone and LT4 were continued on discharge. Final pathology reported silent corticotroph lineage pitNET with low Ki67, immunostaining positive for TPIT, CAM5.2, and negative for ACTH. ACTH-negative SCA are a rare subtype and more likely to have lower ACTH levels, and multiple microcysts on MRI than ACTH-positive SCA. New WHO classification of pitNET highlights the histological typing and subtyping based on immunostaining of pituitary lineage transcription factors as the cornerstone for accurate classification. SCA are more biologically aggressive tumors with a high propensity of recurrence and resistance to conventional treatment. TPIT and ACTH immunostaining significantly improved the diagnosis of SCA and thereby close clinical follow up for early recognition and management of SCA recurrence. Absence of serum markers of recurrence makes this challenging. Presentation: 6/1/2024

7405 A Case of Pituitary Apoplexy in Pregnancy

Abstract Disclosure: Y. Esaki: None. G.E. Vates: None. I. Shafiq: None. Pituitary apoplexy is a rare cause of headache during pregnancy. The prevalence of pituitary apoplexy during gestation and the peripartum period is estimated to be 1 in 10,000 term pregnancies. Approximately 42-47% of these patients were known to have a pituitary lesion especially history of prolactinoma. Here we report a pregnant female developing pituitary apoplexy after discontinuation of dopamine agonist. A 27-year-old female was initially diagnosed with prolactinoma with elevated prolactin of 158.1 ng/ml (3.0-300 ng/ml). MRI revealed a 1.3 cm x 1.5 cm x 1.4 cm pituitary mass with solid and cystic components. Treatment with cabergoline 0.25 mg twice weekly was started. After 2 years of treatment, prolactin was 74.2 ng/ml and the size of the adenoma decreased to 1.0 cm x 1.2 cm x 1.3 cm. One year later, she became pregnant at age 30 and discontinued cabergoline after 7 weeks of gestation. At 12 weeks of gestation, she presented to the Emergency Department for 3 days of severe headaches associated with emesis. The ED work up includes prolactin > 2,000 ng/ml. MRI head without contrast demonstrated an interval increase in size to 1.5 cm x 1.7 cm with hemorrhagic component. Urgent evaluation by a Neuro-ophthalmologist revealed no clinical evidence of optic neuropathy. Blood work showed AM cortisol 2.3 mcg/dl (4.0-22.0 mcg/dl), TSH 0.5 mIU/L (0.4-0.5 mIU/L), FT4 0.6 ng/dl (0.8-1.8 ng/dl). Cabergoline 0.25 mg twice weekly was restarted to control the size of the tumor as well as hydrocortisone and levothyroxine for central adrenal insufficiency and hypothyroidism respectively. Four weeks later, she was 17 weeks pregnant. MRI showed a further increase in the size of the adenoma, now measuring 1.8 cm x 2.0 cm x 1.3 cm. The lesion now extended into the suprasellar cistern, affecting the optic chiasm. She underwent the transsphenoidal resection of the pituitary adenoma at 18 weeks of gestation due to the increase in size of the tumor. The final pathology was consistent with pituitary adenoma, lactotroph cell type, WHO grade 1. MRI obtained 3 months post-operation showed no residual T1 hyperintense tumor signal. There was a cyst-like expansion of the sella turcica with a decreased mass effect on the optic chiasm. She delivered her healthy baby at 40 weeks and 5 days via vaginal delivery. She received stress dose steroid during labor, then was discharged home with hydrocortisone 10 mg twice daily. She is doing well following the delivery and breastfeeding the baby. This case illustrates a rare case of pituitary apoplexy during pregnancy in a patient with prolactinoma. Pituitary apoplexy should be considered as a differential diagnosis when pregnant patients develop an acute, severe headache, especially those with an underlying pituitary adenoma. It is critical to assess and treat the hormonal deficiencies. For prolactinoma, pharmacological therapy can be initiated. Surgery is considered if the medical therapy fails. Presentation: 6/3/2024

7422 Adipsic Diabetes Insipidus Following Pituitary Macroadenoma Resection

Abstract Disclosure: J. Chippior: None. L. Ghalib: None. A 44 year-old female with a PMH of primary hypothyroidism, and a pituitary macroadenoma that was lost to follow up, presented to the ED with a chief complaint of an acute headache and decreased visual acuity involving the right eye over the past year. Patient was found to have a large, homogenous suprasellar mass with the largest dimension measuring 6.3 cm in size, and causing displacement of the optic chiasm. Initial hormonal workup was most notable for elevated prolactin at 128 ng/ml (3.3-26.7 ng/ml), which was slightly lower than when it was previously measured 10 years ago. The patient was taken to the OR for transsphenoidal endoscopic partial resection, but within 24 hours of post-op, she developed hypernatremia at 153 mmol/dL (135-145 mmol/dL) that was suspected to be secondary to diabetes insipidus (DI). In addition, she also suffered several small strokes involving her right midbrain and basal ganglia. She required multiple doses of DDAVP throughout her stay and this was ultimately continued upon discharge. Unfortunately, as follow up MRI had shown residual tumor within the third ventricle, she returned for a 2nd resection but once again suffered additional post-operative complications. The patient experienced additional strokes involving the right frontal and parietal lobes, and her DI became more labile than before, with her serum sodium peaking at 172 mmol/dL. Despite such a high degree of hypernatremia, she did not demonstrate any signs of thirst or any desire to access free water, even after her post-stroke encephalopathy had largely resolved. With less than 100 severe cases documented over the past four decades, it was suspected that the patient had a rare form of DI known as “adipsic DI”. Osmoreceptors within the hypothalamus can trigger the release of ADH or stimulate thirst, with the former requiring a smaller change in serum osmolality to generate such a response. Pituitary surgery involves manipulation of the infundibulum and any inadvertent severing can prevent ADH’s ability to travel from the hypothalamus to the posterior pituitary, subsequently leading to DI. The majority of patients with post-op DI increase their free water intake and subsequently do not develop hypernatremia. Those with adipsic DI lack this compensatory mechanism which leads to the electrolyte disturbance, and carries a higher risk of morbidity and mortality than those with typical DI. Following her second surgery, our patient was discharged with DDAVP once again but this time with a higher dose and frequency. She’s had numerous hospital readmissions since then for altered mental status in the setting of hypernatremia as she still struggles to meet her free water intake and continuously relies on her family for reminders. Though her case is certainly not typical, it highlights the added complexity of managing adipsic DI as it relies not only on DDAVP replacement, but replicating what is supposed to be an innate behavior. Presentation: 6/3/2024

6850 A Case of Anaplastic Thyroid Carcinoma With a Complete Metabolic Response to Pembrolizumab

Abstract Disclosure: E. Tirthani: None. J.T. Kung: None. Background: Anaplastic thyroid carcinoma (ATC) is an aggressive disease with limited therapeutic options and generally poor prognosis. Post-surgery, most patients are treated with a combination of chemotherapy, radiation, and tyrosine kinase inhibitors +/- immune checkpoint inhibitors. We describe a unique case of ATC with a complete metabolic response to pembrolizumab, a selective PD-1 inhibitor, as evidenced by imaging. Clinical Case: A 69-year-old female presented to the clinic for evaluation of a rapidly enlarging neck mass. The initial ultrasound showed a large mixed cystic-solid right thyroid nodule with irregular margins with micro- and macrocalcifications, which was biopsied. Cytology showed discohesive high-grade malignant tumor cells with enlarged nuclei, nuclear hyperchromasia in the background of necrosis, and dense neutrophilic infiltration concerning for ATC. A CT scan of the neck and chest showed a complex cystic thyroid mass with central necrosis and calcification with paratracheal, supraclavicular, and mediastinal lymphadenopathy. MRI of the brain was negative for metastatic disease. The patient underwent a total thyroidectomy with right and left level 6 and 7 neck dissection. Intra-operatively, gross extrathyroidal extension of the tumor was noted to the right carotid, larynx, right recurrent laryngeal nerve, and esophagus, with residual tumor left behind near the larynx. Pathology confirmed stage IVC ATC, positive for PIK3CA, NF1, p53 mutations, and BRAF negative. 90% of tumor cells showed PD-L1 expression on immunohistochemical staining. The post-surgical PET scan showed two discrete, well-defined foci of very intense FDG uptake, corresponding to the right lower cervical and para-esophageal lymph nodes with no evidence of distant metastasis. Systemic chemotherapy with carboplatin and paclitaxel (5 cycles) was initiated with concurrent intensity modulated radiation therapy (total 60 Gy/40 fractions to thyroid bed and bilateral neck). Repeat imaging showed minimal change in the size of the PET-positive lymph nodes. Immunotherapy was initiated and with just 2 cycles of 400 mg IV pembrolizumab, a repeat PET scan was obtained, which showed a complete metabolic response to therapy. Minimal residual FDG activity in the right supraclavicular region was thought to be secondary to posttreatment changes. The patient was able to resume her activities of daily living and had an improvement in appetite. The plan is to continue 400 mg IV pembrolizumab every 6 weeks while cautiously assessing for adverse effects from immunotherapy. Conclusion: It is rare to see a complete metabolic response to therapy with pembrolizumab without concurrent use of tyrosine kinase inhibitors in patients with ATC. A high tumoral PD-L1 expression may be the key to having this kind of dramatic response. Presentation: 6/3/2024

6630 Crooke Cell Pituitary Adenoma Without a Cushingoid Appearance

Abstract Disclosure: J. Hodge: None. S. Idriss: None. I. Jamal: None. R. Panta: None. Background: Crooke cell pituitary adenomas are corticotroph adenomas with Crooke’s cell changes, which are cytoplasmic accumulation of cytokeratin filaments in response to glucocorticoid excess. They are aggressive, invasive tumors, typically macroadenomas, with a high rate of Cushing’s disease and post -treatment (surgery and/or radiotherapy) recurrence. We present a case of Crooke cell pituitary adenoma without a Cushingoid appearance. Clinical Case: A 66-year-old Hispanic male with a 16-year history type II diabetes mellitus with retinopathy, presented with a pituitary macroadenoma at age 60. This was found incidentally when he had a brain CT for evaluation of vertigo. Subsequent brain MRI demonstrated a large 2.4 x 2.0 x 1.7 cm pituitary macroadenoma with extension into the suprasellar cistern and the left cavernous sinus. He was asymptomatic, without Cushingoid features. Hormonal evaluation revealed central hypogonadism and hypothyroidism, mildly elevated prolactin of 39.3 (4-15.2 ng/mL) and morning cortisol level of 12.7 (6-18.4 ug/dL). A 24-hour urine cortisol was normal. He was started on testosterone and thyroid hormone replacement therapy. His diabetes mellitus became progressively difficult to control with a peak HbA1C of 10.1%, about 7 years prior the macroadenoma finding. His HbA1C remained persistently elevated in the 8.1-9.5% range despite being on 6 anti-hyperglycemic agents, including basal insulin. A morning ACTH level 4 years after the initial visit, was 115 (6-50 pg/mL) with a cortisol level of 13.7 (6-18.4 ug/dL). Repeat morning ACTH and cortisol levels 7 months later were very similar. 5 years after the macroadenoma finding, he was noted to have worsening glaucoma, which was believed to be due to optic nerve compression. Therefore, he underwent endoscopic transphenoidal resection for tumor debulking. Pathology supported the diagnosis of Crooke cell corticotroph pituitary adenoma. Repeat brain MRI 3-months post-surgery demonstrated residual tumor, but normal optic chiasm and optic tracts. He had an abnormal dexamethasone suppression test prior to surgery (cortisol 6.4 ug/dL) and continued to do so post-operatively (cortisol 3.7 ug/dL with persistently elevated ACTH). Just prior to his surgery, testosterone replacement therapy was held. Total testosterone level after surgery was normal 309.6 (280-800 ng/dL) and free testosterone 7 (5-21 ng/dL); he remained off replacement therapy. Conclusion: Crooke cell pituitary adenomas are rare with limited data on prognosis and guidance for clinical management. Some patients may have subtle features of hypercortisolism, such as difficult to control diabetes mellitus, without an overt Cushingoid appearance. Presentation: 6/1/2024

7594 Diagnostic utility of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing’s disease after transsphenoidal surgery

Abstract Disclosure: R. Furnica: None. F. Devuyst: None. C. Mathey: None. S. Constantinescu: None. C. De Herdt: None. L. Renaud: None. D.M. Maiter: None. Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing’s disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of [1][1]C-methionine (MET) positron emission tomography coupled with computerized tomography (PET-CT) in localizing the residual corticotroph adenoma. Methods: We retrospectively analyzed the results of all MET-PET-CT performed between May 2002 and November 2023 in patients with a CD persisting or relapsing after TSS, and equivocal (n=14) or negative pituitary MRI findings (n=8). In 15 cases, images obtained from MET-PET were also co-registered with a high-resolution 3D pituitary MRI. All patients had a pathologically confirmed corticotroph tumor, and/or biochemical evidence of early postoperative remission after the first TSS, and/or proven ACTH-dependent Cushing’s syndrome with positive bilateral inferior petrosal sinus sampling. Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 35.5 years at diagnosis. Initial tumors were mostly microadenomas with a mean tumor volume of 15 mm3. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A significant MET standardized uptake value (SUV) in the suspected area of the tumor residue was defined as a ratio ≥ 1.80 relative to cerebellum SUV and was found in 12/22 patients (55%; 4 patients with negative pituitary MRI and 8 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 10 patients and was successful in 6, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate: 8/12). Among the 4 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Exploratory TSS was performed in 4 of the 10 PET negative patients, with no remission. Two patients were treated with GKRS, with remission in 1 case. Among the 4 other patients, bilateral adrenalectomy was performed in one case and adrenal steroidogenesis inhibitors were used in the remaining patients. Conclusions: [1][1]C-Methionine PET-CT imaging can provide valuable diagnostic information to detect a residual active corticotroph adenoma in about half of patients with a persistent or recurrent CD and equivocal or negative MRI results, thereby allowing targeted TSS or radiosurgery with a global success rate of 67% in this selected subpopulation. Presentation: 6/1/2024

9272 Diagnostic utility of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing’s disease after transsphenoidal surgery

Abstract Disclosure: R. Furnica: None. F. Devuyst: None. C. Mathey: None. S. Constantinescu: None. C. De Herdt: None. L. Renaud: None. D.M. Maiter: None. Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing’s disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of [1][1]C-methionine (MET) positron emission tomography coupled with computerized tomography (PET-CT) in localizing the residual corticotroph adenoma. Methods: We retrospectively analyzed the results of all MET-PET-CT performed between May 2002 and November 2023 in patients with a CD persisting or relapsing after TSS, and equivocal (n=14) or negative pituitary MRI findings (n=8). In 15 cases, images obtained from MET-PET were also co-registered with a high-resolution 3D pituitary MRI. All patients had a pathologically confirmed corticotroph tumor, and/or biochemical evidence of early postoperative remission after the first TSS, and/or proven ACTH-dependent Cushing’s syndrome with positive bilateral inferior petrosal sinus sampling. Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 35.5 years at diagnosis. Initial tumors were mostly microadenomas with a mean tumor volume of 15 mm3. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A significant MET standardized uptake value (SUV) in the suspected area of the tumor residue was defined as a ratio ≥ 1.80 relative to cerebellum SUV and was found in 12/22 patients (55%; 4 patients with negative pituitary MRI and 8 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 10 patients and was successful in 6, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate: 8/12). Among the 4 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Exploratory TSS was performed in 4 of the 10 PET negative patients, with no remission. Two patients were treated with GKRS, with remission in 1 case. Among the 4 other patients, bilateral adrenalectomy was performed in one case and adrenal steroidogenesis inhibitors were used in the remaining patients. Conclusions: [1][1]C-Methionine PET-CT imaging can provide valuable diagnostic information to detect a residual active corticotroph adenoma in about half of patients with a persistent or recurrent CD and equivocal or negative MRI results, thereby allowing targeted TSS or radiosurgery with a global success rate of 67% in this selected subpopulation. Presentation: 6/1/2024

Do Anatomical Variations of Sphenoid Sinus Influence Sella Exposure and Residual Disease in Pituitary Surgery? - A Study in an Indian Population.

Introduction Endoscopic transsphenoidal surgery (ETS) is the standard practice in pituitary surgeries. The sellar exposure becomes the main factor which determines the residual disease in ETS. Not many studies can be found in the literature on the influence of anatomical variations of the sphenoid on intraoperative sella exposure. Objective The aim of the current study is to ascertain whether sphenoid sinus variations play a role in sellar exposure and residual tumor volume. Methods This is a prospective study conducted in a south Indian tertiary care center between June 2020 to June 2022, with 21 study participants who were scheduled to have ETS. The relation of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) parameters with the intraoperative area of sellar exposure and residual tumor volume was evaluated. Results Sphenoid sinus dimensions, like presellar width (mean = 1.89 ± 0.51 cm), maximum width (mean = 2.94 ± 1.09 cm), presellar depth (mean = 1.14 ± 0.55 cm), suprasellar depth (mean = 1.08 ± 0.24 cm), infrasellar depth (mean = 2.36 ± 0.92 cm), presellar height (mean = 2.22 ± 0.47 cm), or the 9 internal carotid artery (ICA)-related measures, did not have any correlation with the mean intraoperative area of sellar exposure (0.57 ± 0.28 cm 2 ). Also, the adequacy of sellar exposure did not relate to the residual tumor. Preoperative tumor volume was found to be higher (20.2 [55.3-13.2] cm 3 ) in patients with residual tumor compared with those with no residual tumor (5.9 [6.8-5.2] cm 3 ). Tumor extension had a significant association with the residual tumor volume. Conclusion According to the present study, anatomical variations of the sphenoid sinus do not influence the adequacy of sellar exposure. Further studies need to be undertaken concerning residual tumor volume as well as preoperative tumor volume and extension.

Residual Nodal Burden After Neoadjuvant Chemotherapy in cN1 Breast Cancer Patients with Positive Nodes at Targeted Axillary Dissection.

Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p=0.04), more than three suspicious nodes on initial US (30% vs 13%; p≤0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p=0.0004), and more positive TAD nodes (median, 2 vs 1; p≤0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p≤0.0001), more positive TAD nodes (OR, 1.1; p≤0.0001), larger clipped node metastasis (OR, 1.1; p≤0.0001), and larger residual tumor on pathology (OR, 1.1; p=0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

Concordance of Whole-Slide Imaging and Conventional Light Microscopy for Assessment of Pathologic Response Following Neoadjuvant Therapy for Lung Cancer

Pathologic response is an end point in many ongoing clinical trials for neoadjuvant regimens, including immune checkpoint blockade and chemotherapy. Whole-slide scanning of glass slides generates high-resolution digital images and allows for remote review and potential measurement with image analysis tools, but concordance of pathologic response assessment on digital scans compared with that on glass slides has yet to be evaluated. Such a validation goes beyond previous concordance studies, which focused on establishing surgical pathology diagnoses, as it requires quantitative assessment of tumor, necrosis, and regression. Further, as pathologic response assessment is being used as an end point, such concordance studies have regulatory implications. The purpose of this study was 2-fold, which was as follows: first, to determine the concordance between pathologic response assessed on glass slides and that assessed on digital scans, and second, to determine if pathologists benefited from using measurement tools when determining pathologic response. To that end, hematoxylin and eosin–stained glass slides from 64 non–small cell lung carcinoma specimens were visually assessed for percent residual viable tumor (%RVT). The sensitivity and specificity for digital vs glass reads of pathologic complete response (0% RVT) and major pathologic response (≤10% RVT) were all >95%. When %RVT was considered as a continuous variable, the intraclass correlation coefficient of digital vs glass reads was 0.94. The visual assessments of pathologic response were supported by pathologist annotations of residual tumor and tumor bed areas. In a separate subset of hematoxylin and eosin–stained glass slides, several measurement approaches to quantifying %RVT were performed. Pathologist estimates strongly reflected measured %RVT. This study demonstrates the high level of concordance between glass slides evaluated using light microscopy and digital whole-slide images for pathologic response assessments. Pathologists did not require measurement tools to generate robust %RVT values from slide annotations. These findings have broad implications for improving clinical workflows and multisite clinical trials.

Neoadjuvant immunochemotherapy followed by ex situ lung auto‐transplant (Oto procedure) for central lung cancer: A case report with literature review

AbstractSleeve and double‐sleeve lobectomies are lung‐sparing techniques for treating central lung cancers. However, if the tumour extends to involve the bronchi and vessels, lung auto‐transplantation may be an alternative to pneumonectomy. Neoadjuvant therapy after surgery is the most common strategy for patients with extensive central lung cancer. Herein, we report a case of central lung cancer in a patient who underwent immunochemotherapy as neoadjuvant therapy following lung auto‐transplantation. A 68‐year‐old man with stage IIIA non‐small cell lung cancer and left upper lobe squamous cell carcinoma underwent neoadjuvant immunochemotherapy. Following partial regression, a multidisciplinary team decided on a back‐table procedure with auto‐lung transplantation after pneumonectomy to preserve pulmonary function. The patient had an uneventful recovery and was discharged after three weeks with no residual tumour or lymph node metastases. Lung auto‐transplantation can be successfully performed in non‐lung transplantation centres, potentially broadening treatment options for patients with central lung cancer.

Quantitative assessment of residual tumor is a strong and independent predictor of survival in methylated glioblastoma following radiochemotherapy with CCNU/TMZ.

Maximum tumor resection improves overall survival (OS) in patients with glioblastoma. The extent of resection (EOR) is historically dichotomized. The RANO resect group recently proposed criteria for volumetry-based EOR assessment in patients that were treated according to Stupp´s protocol. The purpose of this study was (1) to investigate the prognostic value of EOR in patients receiving combined chemotherapy with lomustine (CCNU)/temozolomide (TMZ), and (2) to analyse the prognostic performance of binary EOR assessment compared to volumetric assessment. 78 patients with newly diagnosed MGMT-methylated GBM undergoing tumor resection followed by radiochemotherapy with CCNU/TMZ were included in this study. Residual contrast-enhancing (CE) tumor volume after the first resection was measured and its influence on OS and PFS was analysed using uni- and multivariable Cox regression analysis as well as two-sided log rank test. Patients were divided into RTV ≤1 cm³, >1 cm³ - ≤5 cm³ and >5 cm³ following the proposed criteria of the RANO resect group. Prolonged OS was associated with age <60 years, low RTV, and gross total resection (GTR). Residual tumor volume (RTV) had a superior prognostic value compared to binary EOR assessment. Patients with total or near total resection of CE tumor (≤1 cm³ RTV) showed prolonged OS (median 54.4 months, 95% CI 46.94-not reached), with a 5-year survival rate of 49%. Low RTV is associated with increased survival in glioblastoma patients undergoing radiochemotherapy with CCNU/TMZ. This study demonstrates the applicability of the recently proposed RANO resect criteria in this subgroup of patients.

A case of neoadjuvant targeted therapy with pralsetinib for locally advanced lung adenocarcinoma with RET fusion mutation

This case report details the successful treatment of a 68-year-old male patient with locally advanced RET-rearranged lung adenocarcinoma using neoadjuvant pralsetinib. The patient initially presented with a suspicious right upper lobe nodule, which was later diagnosed as lung adenocarcinoma following genetic testing that revealed a RET exon 12 fusion. After 2 months of neoadjuvant treatment with pralsetinib, a significant radiological response was observed, with a reduction in tumor size and metabolic activity. Subsequently, the patient underwent video-assisted thoracoscopic right upper lobectomy and mediastinal lymph node dissection. Postoperative pathological analysis revealed a major pathological response, with only 5% residual tumor cells in the primary lesion and no viable tumor cells in the lymph nodes. Postoperative pathological staging of TNM was ypT1aN0M0, stage IA1(AJCC, 8th edition). The patient recovered well after surgery, demonstrating the potential efficacy of neoadjuvant pralsetinib in locally advanced RET-rearranged lung adenocarcinoma. However, further clinical validation is required to establish the role of neoadjuvant targeted therapy and postoperative adjuvant therapy in this patient population.

Implantable Microneedle-Mediated Eradication of Postoperative Tumor Foci Mitigates Glioblastoma Relapse.

Glioblastoma multiforme (GBM) remains incurable despite multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin (2-3cm) of the initial resected lesion due to the unreachable residual cancerous cells. Here, a completely biodegradable microneedle for surgical cavity delivery glioblastoma-associated macrophages (GAMs)-activating immune nano-stimulator that mitigates glioblastoma relapse is reported. The residual tumor lesion-directed biocompatible microneedle releases the nano-stimulator and toll-like receptor 9 agonist in a controlled manner until the microneedles completely degrade over 1 week, efferently induce in situ phonotypic shifting of GAMs from anti- to pro-inflammatory and the tumor recurrence is obviously inhibited. The implantable microneedles offer a significant improvement over conventional transdermal ones, as they are 100% degradable, ensuring safe application within surgical cavities. It is also revealed that the T cells are recruited to the tumor niche as the GAMs initiate anti-tumor response and eradicate residual GBM cells. Taken together, this work provides a potential strategy for immunomodulating the postoperative tumor niche to mitigate tumor relapse in GBM patients, which may have broad applications in other malignancies with surgical intervention.

Clinical implications of residual normal plasma cells within bone marrow across various disease stages in multiple myeloma.

Residual normal plasma cells (NPCs), which compete with tumor plasma cells, play an important role in multiple myeloma. However, large-scale cohort studies investigating residual NPCs, especially at the minimal residual disease (MRD) phase, are currently lacking. In this study, we conducted a comprehensive investigation into the clinical significance of residual NPCs throughout the entire disease course in 1363 myeloma patients from the NICHE cohort (NCT04645199). Our results revealed that myeloma patients with high baseline NPCs ratio (≥5%) exhibited distinct indolent features, characterized by lower tumor burden, reduced frequencies of cytopenia, immunoparesis, and high-risk cytogenetics. Importantly, high residual NPCs ratio at diagnosis or relapse was independently associated with favorable survival. High absolute percentages of NPCs at undetectable MRD were related with superior clinical benefit and immune reconstitution. At MRD-positive phases, grouping based on NPCs ratio (<50%, 50-90%, ≥90%) demonstrated better risk stratification compared to residual tumor log levels. Based on the time-dependent NPCs ratio trend, we developed a dynamic MRD model that classifies patients into three groups with diverse longitudinal trends, leading to distinct prognoses. Collectively, residual NPCs serves not only as a valuable complementary biomarker for risk stratification but also provides valuable insights on reclassifications and kinetics of MRD.

Cerium as a crystalline phase stabilizer of α-TCP and its hydration and photothermal properties

Bone cement with photothermal properties can treat bone defects caused by bone tumors while killing residual tumor cells or preventing recurrence. In this study, trace amounts of cerium ions were introduced to enhance the crystal stability of α-TCP, thereby improving the hydration properties of α-TCP and obtaining excellent photothermal properties. The experimental results showed that the content of α-TCP in CON-TCP was 96.05 %, and the content of α-TCP in 1% Ce-TCP was 99.77 %, with an increase of 3.87 %; the compressive strength of 0.5% Ce-CPC hydrated for 5d increased from 16.6 MPa±2.18 MPa to 32.16 MPa±2.77 MPa, with an increase of 93.73 %. The temperature of 0.5% Ce-CPC can be raised to 50.9°C in two minutes under the irradiation of 808 nm laser, which is an increase of 31.5% compared with that of 38.7°C in the blank group. Therefore, trace cerium-doped calcium phosphate bone cement has excellent physicochemical and photothermal properties, and it is a promising composite bone cement material, and the results of the present study are expected to be used to treat bone defects in bone tumors.

Minimally Invasive Injectable Gel for Local Immunotherapy of Liver and Gastric Cancer.

Local immunotherapy represents a promising solution for preventing tumor recurrence and metastasis post tumor surgical resection by eliminating residue tumor cells as well as eliciting tumor-specific immune responses. Minimally invasive surgery has become a mainstream surgical method worldwide due to its advantages of aesthetics and rapid postoperative recovery. Unfortunately, the currently reported local immunotherapy strategies are mostly designed to be used after open laparotomy, which go against the current surgical philosophy of minimally invasive therapy and is not suitable for clinical translation. Aiming at this problem, a minimally invasive injectable gel (MIGel) is herein reported loaded with immunotherapeutic agents for gastric and liver cancer postoperative treatment. The MIGel is formed by crosslinking between oxidized dextran (ODEX) and 4-arm polyethylene glycol hydroxylamine (4-arm PEG-ONH2) through oxime bonds, which can be injected through a clinic-used minimally invasive drainage tube and adhered tightly to the tissue. The loaded oxaliplatin (OxP) and resiquimod (R848) can be released constantly over two weeks and resulted in over 75% cure rate in orthotopic mouse gastric and liver cancer model. Collectively, a concept of minimally invasive local immunotherapy is proposed and MIGel is designed for local intraperitoneal cancer immunotherapy through minimally invasive surgery, with good clinical translation potential.