Granular cell tumors of the neurohypophysis with atypical imaging features: a case report and literature review

Abstract

Background

Granular cell tumors (GCTs) of neurohypophysis are rare, the incidence rate of GCTs is higher in female patients compared to male patients, the enlarged GCTs in neurohypophysis can compress the optic chiasm and cause changes in the patient’s visual acuity and visual field. Complete surgical resection is often regarded as the best treatment and can be accomplished via either endoscopic transsphenoidal or open microsurgical approaches, depending on the configuration and topography of the lesion. We report a case of a tumor originating from the pituitary gland with visual field defect as the initial symptom, and with atypical imaging features.

Case description

A 62-year-old female had visual field defect in eyes and symptoms of dizziness. The brain imaging examination revealed a mixed signal quasi-circular tumor in the suprasellar region, the initial imaging diagnosis was craniopharyngioma. Tumor resection surgery was determined to be appropriate. During the operation, we found that the tumor was located behind and below the optic chiasm and compressed the optic chiasm. The tumor was completely resected during the operation and the postoperative pathological results suggested that it was the neurohypophysis granular cell tumor. The patient recovered well after surgery without complications such as diabetes insipidus, electrolyte disorders, or high fever. The visual field was also improved. The three months follow-up MRI of the head showed no recurrence.

Conclusion

GCTs of the neurohypophysis are rare tumors that should be included in differential diagnosis when suprasellar tumors are detected. Surgical resection is an effective treatment option. However, it is important to be aware of complications such as pituitary associated with surgeries. The further imaging characteristics of GCTs still require large-scale clinical research.

Background

Granular cell tumors (GCTs) of the neurohypophysis are rare [1], the incidence rate of GCTs is higher in female patients, with the peak at 40 years old and the average age at 50 years old [2]. Since the optic chiasm is located in the upper part of the pituitary gland, the enlarged GCTs can compress the optic chiasm and cause changes in the patient’s visual acuity and visual field, while changes in visual field tend to occur earlier than visual acuity [3]. Complete surgical resection is often regarded as the best treatment option and can be accomplished via either endoscopic transsphenoidal or open microsurgical approaches, depending on the configuration and topography of the lesion [2]. We report a case of a tumor originating from the pituitary gland with visual field defect as the initial symptom, and with atypical imaging features.

Case description

A 62-year-old female was diagnosed with visual field defect in both eyes and symptoms of dizziness was presented in the month prior. Patient had no history of chronic diseases. The cranial CT examination at outpatient clinic revealed a tumor in the suprasellar region (Fig. 1). The cranial MRI examination identified a mixed signal quasi-circular tumor in the suprasellar region. The initial imaging diagnosis was craniopharyngioma (Fig. 2). Both eyes had visual acuity of 0.8, with varying degrees of visual field defects in both eyes. The visual field defects were mainly bilateral temporal (Fig. 3). The laboratory tests for pituitary related hormones were normal. After discussing with the patient and consult with the family, a tumor resection was determined to be the best treatment option. Due to the tumor’s location in the suprasellar region, the fronto-basal interhemispheric approach was used for the tumor removal. A conventional coronal incision was performed on the patient in a supine position (Fig. 4). During the operation, it was found that the tumor was in the lower back of the optic chiasm and compressing the optic chiasm. The boundary between the tumor and the surrounding tissue was clear, and the tumor was completely resected during the operation (Fig. 5). Further postoperative CT and MRI confirmed the complete resection (Fig. 6). The postoperative pathological results suggested that the removed tumor was neurohypophysis GCT (Fig. 7). Immunohistochemistry values were S100 (+), CD34 vascular (+), Ki67 low expression, CK (-), CD68 (-), Syn (-), CD56 (-), GFAP (-), and SOX-10 (-). The patient recovered well after surgery without complications such as diabetes insipidus, electrolyte disorders, or high fever. After surgery, pituitary related hormones were rechecked, and except for a slight decrease in glucocorticoids, all other hormones were normal. The visual field defect also improved. The three months follow-up MRI of the head showed no recurrence.

Fig. 1.

The cranial CT suggested a tumor in the suprasellar cistern, with uneven density, with a low density area visible in the center, with a diameter of approximately 1.6 cm (A and B). The main body of the tumor was located in the suprasellar region (C and D)

Fig. 2.

The cranial MRI suggested a tumor in the suprasellar region, with no significant mass effect. The edge of the tumor showed equal signals on T1 and T2, while the central part of the tumor showed mixed signals (A and B). After enhancement, the central part showed significant enhancement, while the edge part showed mild enhancement, and the tumor compressed the optic chiasm (C and D)

Fig. 3.

Visual field examination suggested a temporal visual field defect in both eyes

Fig. 4.

During the surgery, we used a coronal incision (A). And in order to fully expose the tumor, the bone flap crossed the midline (B)

Fig. 5.

Under the microscope, the patient underwent lamina terminalis fenestration, the tumor was located behind and below the optic chiasm. The tumor was grayish white, soft, and had a clear boundary with surrounding tissue, which was easy to peel off (A). Surgery was performed to remove the tumor completely and specimens were taken for pathological diagnosis (B)

Fig. 6.

Postoperative cranial CT revealed a small amount of postoperative bleeding in the surgical area (A and B). Postoperative enhanced cranial MRI revealed postoperative changes in the suprasellar region, and no abnormal enhancement lesions were found in the surgical area (C and D)

Fig. 7.

Pathological specimens stained with hematoxylin-eosin staining showed a large number of cells containing eosinophilic granules, and the postoperative pathological results suggested that it was granular cell tumor of the neurohypophysis. A Low magnification view showing tumor cells arranged in sheets with abundant eosinophilic granular cytoplasm (H&E, ×100). B Higher magnification demonstrating polygonal tumor cells with distinct cell borders and granular cytoplasm; note the small, uniform nuclei and areas of clear cell change (H&E, ×200). C Interface between tumor tissue (left) and adjacent fibrous stroma with spindle cells (right), showing the well-demarcated nature of the lesion (H&E, ×100). D High magnification revealing tumor cells with abundant granular cytoplasm and small, round nuclei; note the presence of plexiform vascular structures within the fibrous stroma (H&E, ×200)

Discussion

GCTs of the neurohypophysis are rare in clinical practice, so the process of understanding them is relatively long. In the past, GCTs of the pituitary were considered to have an unknown origin [4]. Until 2013, some research works showed that GCTs of the pituitary were variants of pituicytomas (PITUIs), tumors arose from pituicytes of the posterior lobe [5]. Some rare pituitary tumors such as GCTs then gradually started to be classified. Utilizing more advanced technology including the next-generation sequencing, DNA methylation profiling, and copy number analysis, Schmid et al. [6] was able to confirmed GCTs as a subtype of PITUIs.

GCTs in neurohypophysis are often asymptomatic. When symptomatic, the most common presenting symptom of GCTs is ophthalmologic deterioration, including decreased visual acuity, diplopia, and bitemporal hemianopia [7]. The initial symptom of the patient in our case study was bilateral temporal visual field defect, accompanied by dizziness without symptoms such as polyuria, altered libido, nausea or vomiting. For suprasellar lesions, the presented symptoms seemed to have little specificity. The tumors of the suprasellar region, although varied in pathology, share many clinical similarities because of their anatomic location [8]. Our case study suggested that the presented clinical features of GCTs sometimes may not be able to help the diagnose of suprasellar tumors.

Due to the rarity of GCTs, preoperative and intraoperative diagnosis can be challenging, and misdiagnosis may not be unusual. Based on Warmuth Metz [9], a tumor in the suprasellar region with cysts with high T1-signal showing marginal contrast enhancement, a solid component, and calcifications is very likely a craniopharyngioma. Such imaging features were presented in our case study. So, our preoperative prediction was craniopharyngioma, but the postoperative pathology was GCTs. We conducted thorough literature research on the imaging manifestations of GCTs. During our research, some studies [2, 7, 10–12] suggested that isointense on T1, hypointense/isointense on T2, homogeneous or heterogeneous enhancement, and hyperattenuation on CT were imaging features. The lack of T2 hyperintensity became a potentially reliable differentiating characteristic [2]. However, in our case study, which was different from previous studies [2, 7, 10–12], there was a hyperintensity on T2, which was considered as cystic changes. Cystic changes and calcification are relatively rare [7, 12]. The GCT of cystic lesions is also a unique feature of this report. Therefore, cystic changes and calcification cannot exclude GCTs. The radiologic features of GCTs were relatively nonspecific, different contents of mucoprotein might have contributed to various imaging features [7, 12].

Most GCTs consist of oval or polygonal tumor cells with abundant cytoplasm which are loaded with numerous eosinophilic granules [7, 13]. Such pathological manifestations are consistent with our case study. Our findings in immunohistochemistry showed varying results compared to the past findings. We found that S100 protein and CD34 vascular were positive, while CK, CD68, Syn, CD56, GFAP and SOX-10 were negative. Ki67 expression of was low [7], which was consistent with the general finding in most GCTs. Low Ki67 often leads to the slow growth of most GCTs. Our case study identified low S100, which was consistent with other past case studies in GCTs [7, 14]. Dysregulated expression of multiple members of the S100 family is a common feature of human cancers, with each type of cancer showing a unique S100 protein profile or signature [15]. Unfortunately, we failed to further differentiate S100 protein subtypes. Our case study did not detect CD68 expression which was inconsistent with the past studies [7, 14]. Therefore, further genomic characterization of GCTs of the posterior pituitary may require wider range of research and larger number of case studies. However, the lack of CD68 expression might contribute to the atypical imaging features observed in this case.

CD68 is a lysosomal glycoprotein routinely expressed by mature cells; its loss suggests a low lysosomal biogenesis or an immature vacuolar phenotype [14, 16]. And CD68 deficiency results in a specific decrease in the levels of granulin E [17], as a result, the activity of cathepsin D is affected, leading to an increase in lysosomal membrane tension [18]. Incomplete cathepsin D causes the endosomal-limiting membrane to buckle inward, generating multivesicular body (MVB) [19]. MVB is enriched in aquaporins [20], leading to a marked increase in water permeability. Ultimately, this speculative process is putatively proposed to account for the cystic lesion observed on imaging. Nevertheless, no Western blot, electron microscopy or functional lysosomal assays were performed in the present case; direct validation of this hypothetical cascade is required.

Endoscopic transsphenoidal or open microsurgical approaches could both be options for operation in the case of GCTs, but compared with pituitary adenomas, the transcranial procedure has been used more widely [2, 12]. One of the reasons perhaps is that transcranial procedure tends to have better control on hemostasis [12]. This was also the main reason for the use of the treatment procedure in our case study. In addition, the microscope provides high-power magnification and a three-dimensional stereoscopic view, facilitating meticulous dissection of the cyst wall from adjacent neural and vascular structures, enabling more complete cyst-wall removal and reducing the risk of recurrence [21, 22]. The objective of our surgery was complete excision, but the surgery was not able to sacrifice the stalk in complete excision [2, 7, 12]. In our case, it was not practically possible to achieve complete tumor excision without damaging the pituitary stalk. We found that there was no obvious adhesion between the tumor and the surrounding structures, so we tried to achieve complete resection as much as possible. However, if the surgery proceeds, certain amount of postoperative bleeding and reduced glucocorticoids would have been unavoidable. Therefore, comprehensive evaluation and careful design of the entire treatment course were necessary to determine whether a complete resection should be performed, and sometimes subtotal resection may be acceptable to achieve a better risk benefit ratio [7]. In our case, we have achieved complete resection of the tumor.

Regarding the utility of post-operative radiation therapy, Becker [23] believes that radiation therapy has little or no benefit. But a study [24] suggested that patients with GCT received with occasional post-operative radiation therapy. A systematic review [25] suggested that 25% of patients with persisted or recurred posterior pituitary tumors received radiation therapy. Therefore, the role of radiotherapy is in fact still debatable [26]. In our case, radiotherapy after the surgery was unnecessary because we have achieved complete resection of the tumor.

To more intuitively illustrate the rarity of the present case, we reviewed GCTs located in or around the sellar region reported between 2013 and 2021 and identified 299 cases (Table 1). Only 3 cases exhibited simultaneous T2 hyperintensity, negative CD68 staining, and negative S100 staining; however, none of them explored the immunohistochemical or molecular basis of the T2 hyperintensity. We therefore believe that reporting this atypical patient will provide a new reference for future differential diagnosis.

Table 1.

Sellar region granular cell tumors reported 2013–2022: A 10-Year multicenter Case-series summary

First author (year)	Patients (n)	T2 hyperintensity (n)	Surgical approach (TC/TS)	CD68 (+/–)	S100 (+/–)
Orning et al. (2013) [10]	1	0	0/1	1/0	1/0
Piccirilli et al. (2014) [26]	1	0	0/1	NA	1/0
Li et al. (2016) [27]	4	0	2/2	NA	4/0
Ahmed et al. (2017) [28]	141	NA	45/33	NA	NA
Han et al. (2018) [11]	6	1	NA	NA	NA
Polasek et al. (2018) [2]	44	2	25/15	12/1	24/6
Zhang et al. (2018) [7]	98	4	43/23	12/3	32/12
Hong et al. (2021) [1]	1	NA	0/1	1/0	1/0
Kandregula et al. (2021) [12]	3	0	2/1	3/0	NA
Total (n = 299)	299	7	117/77	29/6	63/18

NA not available, TC transcranial, TS transsphenoidal

Limitations

The hypothetical link between CD68 negativity and cystic T2-hyperintensity is based solely on immunohistochemical absence and literature-based in-silico reasoning; we did not perform molecular, ultrastructural or functional studies to confirm this pathway. This constitutes an inherent limitation of our report.

Conclusion

GCTs of the neurohypophysis are rare tumors that should be included in differential diagnosis when suprasellar tumors are detected. Surgical resection is an important treatment method, but it is important to be cautious of pituitary complications. The further imaging characteristics of GCTs still require some larger scale clinical research.

Abbreviations

GCTs

Granular cell tumors

PITUIs

Pituicytomas

CK

Cytokeratin

Syn

Synuclein

GFAP

Glial fibrillary acidic protein

SOX-10

SRY-related HMG-box 10

MVB

Multivesicular body

Authors’ contributions

Li Ao, Gao Peng, and Tian Weidong conceived and designed the study, collected and analyzed the data, and drafted the manuscript. Zhou Min and Zeng Jie assisted in writing and critically revised the manuscript. Chen Mengfei supervised the study and critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

Funding

This study was supported by the Natural Science Foundation of Ningxia (grant number 2024AAC03554) and CAAE Epilepsy Research Fund-UCB Fund (grant number CU-2024-055). This work was also supported by the Doctoral Research Fund (grant number BS202103), the University Autonomous Research Project (grant number ZZZC202181), the Cohort Study Construction Project (grant number 2025DLYJ01), and the XPCC Guiding Project (grant number KY000302).

Data availability

All data and materials reported in this study are included in this published article.

Declarations

Ethics approval and consent to participate

The patient was treated in accordance with the Declaration of Helsinki. The patient provided informed consent for all procedures. Informed consent was obtained from the patient for inclusion in this study.

Consent for publication

Written informed consent for publication of this case report and the accompanying images was obtained from the patient. A copy of the written consent is available for review by the Editor of this journal.

Competing interests

The authors declare no competing interests.