Naoko Inoshita

Pituitary metastases are uncommon, and most cases originate from breast or lung cancer. Tumor-to-tumor metastasis, in which one neoplasm metastasizes into another, is particularly rare in the sellar region. We report a 66-year-old man with metastatic sigmoid colon adenocarcinoma treated with modified FOLFOX6 (5-fluorouracil, L-leucovorin, and oxaliplatin) plus panitumumab; extracranial disease was controlled, whereas a sellar mass initially suspected as a pituitary adenoma slowly enlarged over 2 years. Endocrine testing showed anterior hypopituitarism without arginine vasopressin deficiency. Endoscopic transsphenoidal surgery was performed for continued enlargement and diagnostic uncertainty. Histopathology demonstrated a gonadotroph pituitary adenoma infiltrated by colorectal adenocarcinoma, with extensive intermingling of the 2 components rather than discrete nests, favoring tumor-to-tumor metastasis over a collision tumor. The metastatic component consisted of viable tumor cells without necrosis or convincing treatment effect despite prolonged chemotherapy. This case underscores that metastatic tumor within a pituitary adenoma may enlarge despite favorable systemic therapy outcomes. Metastasis should therefore remain a key differential diagnosis for a sellar mass radiologically suggestive of a pituitary adenoma.

Male lactotroph pituitary neuroendocrine tumors (PitNETs) are often considered more aggressive than those in women, but surgically treated cohorts are highly selected and may reflect differences in presentation and indication for surgery. We examined whether advanced clinical presentation in surgically treated lactotroph PitNETs is accompanied by distinct pathologic features. We reviewed 43 patients who underwent surgery for lactotroph PitNETs between 2018 and 2023 at a high-volume referral center. Cases were classified by surgical indication as preference for surgery/intolerance to dopamine agonists (P/I, n=26), resistance with hormonal symptoms (R/H, n=10), and resistance with mass effect (R/M, n=7). Clinical, radiologic, and pathologic parameters, including Ki-67, cytokeratin (CAM5.2), estrogen receptor, somatostatin receptor 2/5, and O6-methylguanine-DNA methyltransferase, were compared. Postoperative endocrinological remission was assessed at the last follow-up (median: 34 mo). All tumors were prolactin-immunoreactive, confirming lactotroph differentiation. Patients in the R/M group were older (median: 56 y), predominantly male (71.4%), and had larger tumors (median: 26 mm) with more frequent cavernous sinus invasion (Knosp grade 4, 85.7%) than those in the other groups. Long-term endocrinological remission differed significantly by indication (P/I, 88.5%; R/H, 80.0%; and R/M, 0%). In contrast, Ki-67 labeling index did not differ significantly across groups (P/I, 1.3%; R/H, 1.5%; and R/M, 2.6%; P =0.598), and no clear between-group differences were identified in CAM5.2 pattern, estrogen receptor, somatostatin receptor 2/5, or O6-methylguanine-DNA methyltransferase status. These findings suggest that the clinically most advanced surgical cases are not matched by distinct pathologic differences in the markers assessed and that the apparent aggressiveness of male-predominant mass-effect cases should not be interpreted solely as reflecting intrinsically aggressive tumor biology.

The ectopic secretion of growth hormone (GH) or growth hormone-releasing hormone (GHRH) is responsible for fewer than 1% of acromegaly cases. Furthermore, within this small population, GHRH-secreting pheochromocytomas/paragangliomas (PPGLs) are even rarer. A 57-year-old Japanese woman presented to our hospital for treatment of a large left-sided pheochromocytoma (PCC). A physical examination revealed enlargement of the nose and lips as well as macroglossia, thereby raising the suspicion of acromegaly, which was biochemically confirmed by a 75-g oral glucose tolerance test. Magnetic resonance imaging demonstrated a slightly enlarged pituitary gland but no definitive tumor. A left adrenalectomy was performed after careful dose titration of doxazosin and metyrosine. Postoperative biochemical improvement of GH excess and immunohistochemical analysis of the resected tumor confirmed the diagnosis of GHRH-secreting PCC. Given the possibility that PPGLs produce various ectopic hormones and peptides, thorough physical examinations remain fundamental for the accurate diagnosis and optimal management of patients with these tumors.

Gender equity has become an important issue in academic medicine, but data on gender distribution in subspecialty medical societies remain limited. We analyzed gender distribution in membership, leadership positions, and conference participation in the Japanese Society for Hypothalamic and Pituitary Tumors (JSHPT). Membership data as of March 2025 (n = 860) were examined, and gender distribution among speakers and session chairs at the 36th Annual Meeting of the JSHPT was evaluated using the publicly available abstract book. Among all members, 128 (14.9%) were women. Women accounted for 6.6% of councilors and 5.6% of board members and auditors, and only one woman has served as Annual Meeting president among the first 36 annual meetings. At the 36th Annual Meeting, women represented 18.6% of presenters in general oral sessions, but only 5.0% of session chairs in general oral sessions and 3.7% of chairs in other sessions. Women also accounted for 36.4% of members with less than 1 year of membership. These findings suggest that, although women remain underrepresented in leadership positions within the society, female participation may be increasing among newer members, and women are actively participating as conference presenters. Continued efforts to increase opportunities for women to serve as session chairs and to encourage qualified women to apply for councilor positions may contribute not only to a more equitable academic environment, but also to the vitality and future leadership of the field.

Purpose: Understanding the muscular structure of the anal canal is crucial for the diagnosis and treatment of anorectal diseases. Treitz muscle is a vital yet poorly understood component. It supports the anal venous plexus and contributes to anal cushion formation. However, its anatomical details remain unclear, and various theories suggest different origins for its muscle bundles, which affects our understanding of the pathophysiology of hemorrhoids. In this study, we sought to clarify the origin and localization of Treitz muscle to provide an anatomical foundation for understanding anal function.Methods: In this descriptive cadaveric study of 11 cadavers, we performed macroscopic examinations and immunohistological analyses on tissues from the anterior, lateral, and posterior walls of the anal canal. The origin and localization of Treitz muscle were qualitatively evaluated.Results: Treitz muscle is a smooth muscle formed by a directional change in the muscle bundles of the internal anal sphincter, running longitudinally along its surface. A shift in the direction of muscle bundles originating from the internal anal sphincter, giving rise to Treitz muscle, was frequently observed in the anterolateral wall of the anal canal.Conclusion: In summary, Treitz muscle, a smooth muscle extending from the internal anal sphincter, is considered part of the muscularis propria. Its directional shift was localized to the anterolateral wall, indicating that Treitz muscle is not uniformly distributed around the anal canal. This site-specific localization may influence the risk of hemorrhoids or cancer invasion depending on its anatomical position.

Pituitary neuroendocrine tumors (PitNETs) are generally benign, but a small subset may demonstrate aggressive behavior or undergo malignant transformation. Neuroendocrine carcinoma (NEC), defined as a high-grade, poorly differentiated neuroendocrine neoplasm, is extremely rare in the pituitary, and its existence as a primary entity remains controversial. We report two cases of corticotroph PitNETs in female patients with Cushing disease, in which NEC components emerged several years after radiotherapy. Case 1 presented as an invasive macroadenoma with cavernous sinus invasion, and Case 2 as a 5 mm microadenoma. In both cases, recurrent tumors developed following subsequent radiotherapy. NEC components exhibited marked nuclear pleomorphism, necrosis, elevated Ki-67 indices, diffuse p53 expression, and loss or reduction of ACTH and TPIT expression. In Case 2, faint TPIT expression and discontinuous tumor growth within the sella raised the possibility of a metastatic NEC to the pituitary could not be excluded. These cases highlight the emergence of NEC features in corticotroph PitNETs, most likely as a result of post-radiotherapy transformation. However, due to faint TPIT expression and an unusual tumor distribution in Case 2, the possibility of a primary NEC or metastatic neuroendocrine neoplasm from another organ cannot be definitively excluded.

Background: Nodular fasciitis (NF) is a self-limiting mesenchymal neoplasm. Although it can occur in various parts of the body, its presence within the sphenoid sinus is extremely rare in adults. To the best of our knowledge, only one other case has been reported in the English literature. Because of its rapid growth and potential to mimic malignant tumors, accurate diagnosis and timely treatment are essential. Case Description: We report a case of a 58-year-old man who presented with visual disturbance in the right eye. Computed tomography and magnetic resonance imaging revealed a mass lesion in the sphenoid sinus, with erosion of the bony wall of the right optic nerve canal. The mass was completely removed through an endoscopic transnasal transsphenoidal approach, both for histopathological diagnosis and optic nerve decompression. Pathological examination confirmed the diagnosis of NF. Postoperatively, the patient’s visual field improved significantly. Conclusion: This case highlights NF as a rare but important differential diagnosis in patients presenting with visual impairment due to a mass in the paranasal sinus. In symptomatic cases, early surgical intervention should be considered to prevent symptom progression and ensure an accurate diagnosis.

Objective: Many patients with pituitary neuroendocrine tumours (PitNETs) containing beta (β) thyroid‐stimulating hormone (TSH)‐immunopositive cells, without syndrome of inappropriate secretion of TSH (SITSH), show a significant reduction in TSH levels following surgical removal of the tumour‐like functioning thyrotroph PitNET. We evaluated the pathophysiological and clinical characteristics of TSH‐positive cells in PIT1‐lineage PitNETs in patients without the syndrome of inappropriate secretion of TSH.Design: Retrospective cohort study.Patients and Mesurements: Overall, 165 patients diagnosed with PIT1‐lineage PitNETs without SITSH between April 2018 and July 2023 at Moriyama Memorial Hospital were reviewed. They were categorised into three groups based on the rate of βTSH‐immuno‐positive cells in their PitNETs: strongly positive group with 10% or more βTSH‐immuno‐positive cells, weakly positive group with less than 10%, and negative group. Clinical data from these groups were compared.Results: Patient age, sex, and tumour size did not differ significantly among the groups. Most of the weakly positive cases had acromegaly, whereas many of the strongly positive cases had clinically nonfunctioning tumours. Preoperative TSH levels were slightly higher in strongly positive cases than in the other groups but fell within the normal range postoperatively, whereas postoperative TSH levels were significantly lower across all groups. The degree of TSH reduction postoperatively was significantly higher in the strongly positive group.Conclusions: In the strongly positive group, TSH levels decreased significantly after surgery, whereas no such decrease was observed in the other two groups, suggesting that thyrotrophs in strongly positive PitNETs are TSH‐producing, similar to clinically functioning thyrotroph PitNETs.

Purpose: Rathke’s cleft cyst can lead to visual and pituitary dysfunction. Surgical decompression may alleviate these issues, but the decision to operate remains controversial because of the risk of worsening function. Methods: A retrospective analysis was conducted on 80 patients who underwent endoscopic transnasal transsphenoidal surgery for Rathke’s cleft cyst from April 2018 to April 2024. Clinical outcomes were assessed using magnetic resonance imaging, intraoperative findings, and histopathology to evaluate factors associated with recovery. Results: After a median follow-up of 13.5 months (interquartile range: 6-30.8 months), anterior pituitary function significantly improved in patients with cysts that did not compress the optic nerve and had minimal thinning of the ganglion cell layer-inner plexiform layer (P < .05). Arginine vasopressin deficiency occurred significantly more often in patients with preoperative adult GH deficiency, a history of surgery, and evidence of inflammation in specimens on pathology (P < .05). Retinal nerve fiber layer thickness correlated with visual field impairment both before and after surgery, suggesting it may predict visual recovery. Conclusion: Decompression of Rathke’s cleft cysts can improve anterior pituitary function in patients with smaller cysts and minimal optic nerve pressure. Visual function will likely improve in those with minimal optic nerve fiber layer thinning. Therefore, preoperative optical coherence tomography and visual field testing are mandatory to set expectations regarding potential improvement in vision and anterior pituitary function following surgery. Patients with preoperative adult GH deficiency and a history of surgery are at higher risk of developing postoperative arginine vasopressin deficiency.

The 2017 World Health Organization classification described aggressive pituitary neuroendocrine tumor (PitNET) as “a tumor with strong invasiveness and rapid growth, which is difficult to treat with surgery, radiation therapy, or drug therapy,” which remains a challenge in the treatment of pituitary tumors. Currently, temozolomide (TMZ) is the first-line treatment for aggressive PitNET. However, it is not yet covered by insurance in Japan. Additionally, O6-Methylguanine-DNA Methyltransferase (MGMT) expression can lead to treatment resistance, further complicating treatment selection. We previously demonstrated the effectiveness of combination therapy with capecitabine (CAPTEM) in several cases of aggressive PitNETs. The present study described our experiences with TMZ in 13 patients with aggressive PitNETs (including four patients administered CAPTEM). Pathological examination revealed eight corticotroph, four lactotroph, and one somatotroph tumors. Of these, seven patients are still receiving treatment, and six patients have terminated treatment. The reasons for discontinuation were poor efficacy (three patients), financial reasons (two patients), and patient preference (one patient). No patients required treatment discontinuation owing to adverse events. Furthermore, one case of a lactotroph tumor, which achieved remission with CAPTEM but was discontinued after three years for financial reasons, remains in remission on imaging and maintained normal PRL levels for 15 months after discontinuation. The most significant issue is off-label use. Concern exists that financial constraints may prevent future patients from using TMZ.