Intracranial lipomas are benign tumors that may occasionally be found in the suprasellar cistern while pituitary adenomas are far more common brain tumors. Pituitary adenomas may rarely coexist with other intracranial tumors in the sellar-suprasellar region. We share a unique case of a patient with coexisting non-functioning pituitary adenoma and sellar-suprasellar lipoma presenting with blurring of vision.

We report a 55-year-old male presenting with a two-year history of blurring of vision with findings of a 2.7 x 3.0 x 3.2 cm homogeneously enhancing lobulated isointense mass on the sellar-suprasellar region. Hormonal workups revealed low cortisol and mildly elevated prolactin. He initially underwent endonasal transsphenoidal excision of the tumor which revealed to be a lipoma on histopathology. Due to minimal improvement of vision from the subtotal excision, he underwent repeat surgery through the transcranial approach which in turn showed a pituitary adenoma.

The co-occurrence of two sellar-suprasellar tumors with different histology is rare, as most of the evidence is based on only a handful of case series. Intracranial lipomas result from persistence and abnormal differentiation of the meninx primitiva during the development of the subarachnoid cisterns. On the other hand, pituitary tumorigenesis is still largely unclear but appears to involve multiple tumor suppressor genes, oncogenes, cell cycle deregulation factors, and miRNAs. Given the differing pathogenesis of each tumor type, the coexistence may only be coincidental. The best surgical approach in this situation is unknown but the focus is on complete excision of the adenoma.

BACKGROUND AND OBJECTIVE

A parachiasmal lesion is defined as a mass or growth arising from structures around or near the chiasm. Ophthalmologic signs and symptoms may be observed in such condition, such as blurring of vision, visual field defects, and binocular double vision. The primary objective of this study was to describe the presenting ophthalmologic signs and symptoms of parachiasmal lesions among patients consulting at a single institution in the Philippines.

This was a single-center, retrospective, cohort study. Medical records of patients with parachiasmal lesions seen in the Neuro-Ophthalmology clinic of a tertiary Philippine hospital from January 2014 to December 2019 were reviewed. Clinical profile, neuro-ophthalmologic presentation, diagnosis, management, and visual outcomes were summarized by descriptive statistics.

One hundred thirty-three (133) patient records satisfied the study criteria. Most common presenting symptoms were blurring of vision. headache, and loss of vision. Visual acuity at initial visit ranged from 20/20 to no light perception. A relative afferent pupillary defect was present in half of the study population. Almost half presented with normal-looking discs or disc pallor. Bitemporal hemianopia is the most common visual field defect pattern seen in both confrontation and automated visual field testing. Histopathology was significantly associated with visual outcome.

Parachiasmal lesion should be suspected in patients who complain of unilateral blurring of vision, and those who present with normal or pale optic discs. Pituitary adenoma is the most common radiologic and histopathologic diagnosis. Visual outcome after intervention has improved or remained stable in two-thirds of patients; visual recovery is multi-factorial, which is influenced by duration, surgery, and histopathology.

BACKGROUND AND OBJECTIVE

Prolactinoma is the most common functioning tumor of the pituitary gland. While its clinical course and outcomes among different populations have been vastly described in the past, data of prolactinoma among Filipinos has not been explored. This paper aims to describe the clinical profile and outcome of prolactinoma among adult Filipino patients.

We conducted a retrospective cohort study including 41 patients with prolactinoma seen at the Philippine General Hospital. The clinical profile, cranial imaging features, treatment modalities given, and their outcomes over a mean follow up of 16 months were evaluated.

The mean age at diagnosis was 36.76 ± 13.99 years. Majority of our cohort were females. Macroprolactinoma were found in 75.61% and giant prolactinoma in 9.76%. The remaining 12.2% were mixed GH and PRL secreting tumors. Most common symptoms at presentation were blurring of vision, headache, and amenorrhea. Median PRL levels was 353 (200-470) ng/ml. Medical therapy with Bromocriptine was the primary treatment modality used in 78% of patients. We found no significant difference between patients who underwent surgical and medical primary treatment modalities in terms of outcomes. At the end of follow up, 82.6% of patients achieved at least more than 50% reduction in their prolactin levels.

Overall, our study showed that adult Filipino patients with prolactinoma have a larger tumor size at diagnosis and a lower rate of improvement of gonadal function after treatment. There were no statistically significant differences in clinical and biochemical outcomes between the treatment modalities used.

Intracranial lipomas are benign tumors that may occasionally be found in the suprasellar cistern while pituitary adenomas are far more common brain tumors. Pituitary adenomas may rarely coexist with other intracranial tumors in the sellar-suprasellar region. We share a unique case of a patient with coexisting non-functioning pituitary adenoma and sellar-suprasellar lipoma presenting with blurring of vision. We report a 55-year-old male presenting with a two-year history of blurring of vision with findings of a 2.7 x 3.0 x 3.2 cm homogeneously enhancing lobulated isointense mass on the sellar-suprasellar region. Hormonal workups revealed low cortisol and mildly elevated prolactin. He initially underwent endonasal transsphenoidal excision of the tumor which revealed to be a lipoma on histopathology. Due to minimal improvement of vision from the subtotal excision, he underwent repeat surgery through the transcranial approach which in turn showed a pituitary adenoma. The co-occurrence of two sellar-suprasellar tumors with different histology is rare, as most of the evidence is based on only a handful of case series. Intracranial lipomas result from persistence and abnormal differentiation of the meninx primitiva during the development of the subarachnoid cisterns. On the other hand, pituitary tumorigenesis is still largely unclear but appears to involve multiple tumor suppressor genes, oncogenes, cell cycle deregulation factors, and miRNAs. Given the differing pathogenesis of each tumor type, the coexistence may only be coincidental. The best surgical approach in this situation is unknown but the focus is on complete excision of the adenoma.
Pituitary Neoplasms

Background and Objective: Prolactinoma is the most common functioning tumor of the pituitary gland. While its clinical course and outcomes among different populations have been vastly described in the past, data of prolactinoma among Filipinos has not been explored. This paper aims to describe the clinical profile and outcome of prolactinoma among adult Filipino patients. Methods: We conducted a retrospective cohort study including 41 patients with prolactinoma seen at the Philippine General Hospital. The clinical profile, cranial imaging features, treatment modalities given, and their outcomes over a mean follow up of 16 months were evaluated. Results: The mean age at diagnosis was 36.76 ±13.99 years. Majority of our cohort were females. Macroprolactinoma were found in 75.61% and giant prolactinoma in 9.76%. The remaining 12.2% were mixed GH and PRL secreting tumors. Most common symptoms at presentation were blurring of vision, headache, and amenorrhea. Median PRL levels was 353 (200-470) ng/ml. Medical therapy with Bromocriptine was the primary treatment modality used in 78% of patients. We found no significant difference between patients who underwent surgical and medical primary treatment modalities in terms of outcomes. At the end of follow up, 82.6 % of patients achieved at least more than 50% reduction in their prolactin levels. Conclusion Overall, our study showed that adult Filipino patients with prolactinoma have a larger tumor size at diagnosis and a lower rate of improvement of gonadal function after treatment. There were no statistically significant differences in clinical and biochemical outcomes between the treatment modalities used.
Prolactinoma ; Pituitary Neoplasms ; Prolactin

Male patients with prolactinomas usually present with typical hyperprolactinemia symptoms, including sexual dysfunction and infertility. However, clinical factors related to sexual dysfunction and surgical outcomes in these patients remain unclear. This study aimed to investigate the outcomes of male patients with prolactinomas after transsphenoidal surgery and the risk factors affecting sexual dysfunction. This study was conducted on 58 male patients who underwent transsphenoidal surgery for prolactinomas between May 2014 and December 2020 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. We evaluated the sexual function of patients before and after surgery through International Index of Erectile Function-5 scores, libido, and frequency of morning erection. Of the 58 patients, 48 (82.8%) patients had sexual intercourse preoperatively. Among those 48 patients, 41 (85.4%) patients presented with erectile dysfunction. The preoperative International Index of Erectile Function-5 scores in patients with macroprolactinomas were significantly higher than those in patients with giant prolactinomas (17.63 ± 0.91 vs 13.28 ± 1.43; P = 0.01). Postoperatively, the incidence of erectile dysfunction was 47.9%, which was significantly lower than that preoperatively (85.4%; P = 0.01). Twenty-eight (68.3%) patients demonstrated an improvement in erectile dysfunction. Tumor size and invasiveness were significantly correlated with the improvement of erectile dysfunction. Preoperative testosterone <2.3 ng ml^-1 was an independent predictor of improvement in erectile dysfunction. In conclusion, our results indicated that tumor size and invasiveness were important factors affecting the improvement of sexual dysfunction in male patients with prolactinoma. The preoperative testosterone level was an independent predictor related to the improvement of erectile dysfunction.
Humans ; Male ; Prolactinoma/surgery* ; Erectile Dysfunction/etiology* ; Retrospective Studies ; Sexual Dysfunction, Physiological/complications* ; Testosterone ; Pituitary Neoplasms/pathology*

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups (P=0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.
Humans ; Neuroendocrine Tumors ; Pituitary Neoplasms/pathology* ; Pituitary Hormones ; Growth Hormone/metabolism* ; Keratins

Objective: To investigate the related factors and treatments of delayed cerebrospinal fluid rhinorrhea (CFR) after invasive pituitary adenoma (IPA) surgery. Methods: One hundred and forty-two patients with IPA treated in Tianjin Huanhu Hospital from January 2014 to January 2019 were analyzed retrospectively, including 62 males and 80 females, aging from 38 to 67 years. The clinical data of patients before and after operation were collected. All patients with postoperative CFR underwent endoscopic CFR repair. During the operation, residual or recurrent pituitary adenomas were resected, the dura around the leak was enlarged and the necrotic tissue was removed. For those who still had fluid leakage after repair, the necrotic tissue was cleaned up, the leakage was filled and reinforced under endoscopy. Endoscopic rhinorrhea repair was performed if necessary. The cerebrospinal fluid leak was repaired with multi-layer materials. The related risk factors of delayed CFR after operation were analyzed. SPSS 19.0 software was used for statistical analysis. Results: Among the 142 patients in this group, 64 cases underwent total tumor resection and 78 cases underwent non-total tumor resection. They were followed up for 6 to 72 months. Thirty-one cases had delayed CFR, with an incidence of 21.83%, and occurred between 1 and 5 years postoperatively, with an average of 2.4 years. All 31 patients with delayed CFR underwent endoscopic CFR repair. The nasal endoscopy was rechecked at 2 weeks, 1 month, 3 months and 6 months after operation. Twenty-eight patients were repaired successfully after 1 operation, while 2 patients after 2 operations and 1 patient after 3 operations. These patients were followed up for 6 to 60 months, and no CFR occurred again. Univariate analysis showed that the degree of tumor resection, recurrence, size, texture, postoperative radiotherapy and operator experience were the risk factors of delayed CFR (all P<0.05). Multivariate analysis showed that the degree of tumor resection and recurrence were the highest independent risk factors for postoperative CFR, and tumor size, texture, postoperative radiotherapy and operator experience were the independent risk factors in this study. Conclusions: Delayed CFR after IPA is related to the degree of tumor resection, recurrence, size, texture, postoperative radiotherapy and the operator experience. It is necessary to completely remove the tumor under endoscope, to expand resection of the dura and necrotic tissue around the leak, to repair the defect with multi-layer materials, to follow-up closely and to repair timely after operation.
Adenoma/surgery* ; Adult ; Aged ; Cerebrospinal Fluid Leak ; Cerebrospinal Fluid Rhinorrhea/surgery* ; Female ; Humans ; Male ; Middle Aged ; Pituitary Neoplasms/surgery* ; Retrospective Studies

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.
Adenocarcinoma of Lung/drug therapy* ; Adrenocorticotropic Hormone/therapeutic use* ; Aged ; B7-H1 Antigen/therapeutic use* ; Humans ; Hydrocortisone/therapeutic use* ; Hyponatremia/drug therapy* ; Hypopituitarism/drug therapy* ; Immune Checkpoint Inhibitors ; Lung Neoplasms/pathology* ; Male ; Methylprednisolone/therapeutic use* ; Middle Aged ; Nausea/drug therapy* ; Pituitary Gland/pathology* ; Pneumonia ; Prednisone/therapeutic use* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Prolactin/therapeutic use*