PEDT-3

Background: Germ cell tumors (GCTs) containing a teratoma component is a group of diseases consisting of various pathological conditions such as mature teratoma, immature teratoma, teratoma with malignant transformation, and mixed tumor with other GCTs. There is controversy about the efficacy and safety of radiation and chemotherapy for GCTs with teratoma component other than mature teratomas. Methods: Of 212 cases of GCTs treated at Tohoku University Hospital Neurosurgery from January 1990 to March 2021. In this study, 23 histologically verified GCTs containing teratoma components were included. Pathological findings, recurrence, survival, and late complications were examined. Results: The age of onset was 2 months-21 years (median 10.5 years). Histological diagnosis was mature teratoma alone in 5 cases, mixed GCTs with mature teratoma in 11 cases, immature teratoma in 5 cases, and mixed tumor with mature teratoma and germinoma in 2 cases. Patients except mature teratoma were treated by chemotherapy alone or radiochemotherapy. During follow-up for 7–362 months (median 135 months), 3 patients relapsed. One of these patients was diagnosed with mature teratoma at the time of treatment and did not receive post-treatment, but relapsed as germinoma 21 years later. A review of pathological specimens at the time of initial onset revealed immature teratomas in addition to mature teratomas. Recurrent lesions in 3 cases were controlled by additional treatment, and no deaths due to tumor progression were observed. On the other hand, of the 18 patients who underwent radiochemotherapy, 1 developed primary hypothyroidism and 2 developed thyroid cancer and leukemia. Conclusion: GCTs with teratoma component often contain malignant histological types and require caution when making a pathological diagnosis. In these cases, tumor control can be expected by radiation or chemotherapy, but there is a risk of developing endocrine disorders and secondary tumors, and further studies are needed to optimize treatment.

Evolution of superficial spreading melanoma to resemble desmoplastic melanoma: case report

Desmoplastic melanoma commonly occurs on the head and neck in a pure form, but occasionally, it occurs in a mixed tumor with another type, usually superficial spreading melanoma (SSM), and rarely as a metastasis from a primary SSM. We report here a primary SSM on the leg of a 32-year-old male which metastasised to lymph nodes, and 10 years later recurred at the primary site initially with mixed features but evolving to resemble a uniformly desmoplastic, deeply invasive melanoma. This unusual case has implications for clinical management and is additionally notable for its reversal in behavior, from metastatic to local infiltrative type, correlating with the change in morphology.

Multiple Challenges: An Unusual Case of an Adrenal Mass With Plurihormonal Secretion of Catecholamines and Cortisol in a Patient With Several Neoplasms

Introduction: Simultaneous hypersecretion of both catecholamines and cortisol in one adrenal tumor is rarely seen because cortical cells, which produce cortisol, and medullary cells, which secrete catecholamines, are derived from different germ layers1. Formidable challenges ensue from a tumor with a complex behavior. We demonstrate here the clinical course and multi-modal management of the case of an adrenocortical adenoma which had neuroendocrine differentiation accounting for the excess of both catecholamine and cortisol hormones in a patient with multiple neoplasms. Clinical Case: An adrenal mass was incidentally discovered in a 61-year old female undergoing imaging as part of the metastatic work-up for an esophageal mass. The patient has insulin-requiring diabetes mellitus, hypertension and a history of breast cancer. A right adrenal gland mass, avidly enhancing, measuring 3.8 x 2.7 x 2.7 cm was found on abdominal imaging. The 24-hour urine metanephrine collections were done, and these were more than twice elevated in two instances at 2.516 mg/24 hours and 2.101 mg/24 hours (NV: 0–1 mg/24 hours). An unsuppressed cortisol level at 6.57 μg/dL (NV: ≤ 1.8 μg/dL) was obtained after the 1 mg dexamethasone suppression test. Hypercortisolism was confirmed with an elevated 24-hour urine free cortisol at 312.07 μg/24 hours (NV: 20–90 μg/24 hours). Adrenocorticotrophic hormone (ACTH) was low at 0.90 pg/ml, indicative of the presence of an adrenal form of Cushing’s. Primary aldosteronism was ruled out based on a ratio between plasma aldosterone concentration and plasma renin activity of less than 20. Pre-operative alpha blockade with terazosin was initiated. Right adrenalectomy was done. Histopathology revealed an adrenal mass of cortical origin, atypically staining positively for synaptophysin, which is indicative of neuroendocrine differentiation of the tumor. The patient had better blood pressure and glycemic control after the adrenalectomy. Clinical Lessons: An adrenocortical adenoma very seldom undergoes neuroendocrine differentiation. Pathophysiologic mechanisms include a genetic aberration in cortical cells leading to production of catecholamines2. This case underscores the importance of a comprehensive biochemical evaluation of a patient with an adrenal mass because control of hormonal hypersecretion is essential in reducing cardiovascular risks, morbidity and mortality. References: 1Duan L, Fang F, Fu W, et al. Corticomedullary mixed tumor resembling a small adrenal gland-involvement of cancer stem cells: case report. BMC Endocr Disord. 2017;17(1):9. Published 2017 Feb 13. doi:10.1186/s12902-017-0157-7.2Donatini G, Van Slycke S, Aubert S, Carnaille B. Corticomedullary mixed tumor of the adrenal gland-a clinical and pathological chameleon: case report and review of literature. Updates Surg. 2013 Jun;65(2):161–4. Epub 2012 Jan 7. PMID: 22228558.

A Unique Case of Corticomedullary Mixed Tumor Composed of Both Adrenal Cortical Cells and Pheochromocytes

Introduction or Background: Corticomedullary mixed tumors of the adrenal gland was first described in 1969 by Mathison and Waterhouse. It is defined as a single tumor mass of the adrenal gland that histopathologically has presence of adrenal cortical and medullary cells. Such mixed tumors involving the cortical and medullary components of the adrenal glands are very rare. Clinical Case (including diagnostic evaluation, treatment, and follow-up):A 67 year old woman with a history of hypertension and osteoporosis presents for incidental adrenal adenoma. Hypertension was controlled well with olmesartan 40mg, hctz 25mg, and amlodipine 2.5mg. Abdominal CT scan showed a 2.6 cm enhancing left adrenal nodule with delayed wash- out phase. Biochemical testing showed elevated plasma free metanephrine (132pq/ml, n < or = 57pq/ml) and abnormal 1mg dexamethasone suppression test (10.4mcg/dL, n <2mcg/dL). ACTH was suppressed. Patient underwent left adrenalectomy, after pretreatment with doxazosin. Surgical pathology report showed an unusual neoplasm consisting of a single nodule composed of intermixed aggregates of cortical cells and pheochromocytes displaying morphologic features of adrenal adenoma and pheochromocytoma. Also intermixed with the adenoma was a 3mm myelolipoma. Post surgery, the patient was treated with hydrocortisone for symptoms of adrenal insufficiency. Post surgery, she was able to stop amlodipine and hctz and is on 10 mg olmesartan on alternate days.. She remains on a weaning dose of hydrocortisone at the time of abstract submission. Clinical Lesson(s) or Conclusion(s) (emphasizing the learning point[s] and implications for clinical practice)This unique case report highlights the importance of appropriate workup for incidental adrenal adenoma and keeping in mind the rare possibility of mixed endocrine tumours. A single mixed tumor of the adrenal gland is rare but exhibits distinct morphologic features of both a cortisol producing tumor along with a pheochromocytoma. Furthermore, a concurrent intermixing of a myelolipoma within an adrenal corticomedullary mixed tumor is rarely reported.

Wnt Inhibition Sensitizes PD-L1 Blockade Therapy by Overcoming Bone Marrow-Derived Myofibroblasts-Mediated Immune Resistance in Tumors

Cancer-associated fibroblasts (CAFs) has been recognized as one cause of tumor resistance to immune checkpoint blockade therapy, but the underlying mechanisms still remain elusive. In the present study, a bone marrow-derived CAF (BMF) -rich tumor model is successfully established by subcutaneously mixed inoculation of BMFs and tumor cells into mice and the BMF-mixed tumor xenografts are demonstrated to be resistant to anti-PD-L1 antibody immunotherapy compared to the mere tumor xenografts. In vitro assays via the co-culture system of BMFs and tumor cells indicate that the co-cultured BMFs are induced to overexpress PD-L1, while there is no such a phenomenon in the co-cultured cancer cells. The further knock-out of PD-L1 in BMFs rescues the sensitivity of BMF-mixed tumor xenografts to PD-L1 blockade therapy. Mechanistically, via the microarray assay, we identify that the upregulation of PD-L1 in BMFs stimulated by cancer cells is medicated by the activation of the Wnt/β-catenin signaling pathway in BMFs. Moreover, the administration of Wnt/β-catenin signaling inhibitors, including XAV-939 and Wnt-C59, distinctly inhibits the upregulation of PD-L1 expression in the co-cultured BMFs. The further combination administration of XAV-939 significantly potentiates the therapeutic outcome of PD-L1 blockade therapy in BMF-mixed tumors. In summary, our study demonstrates that Wnt inhibition augments PD-L1 blockade efficacy by overcoming BMF-mediated immunotherapy resistance.