|Ahead of print
Pituitary Carcinoma in Paediatric Age Group: A Rare Case Report
Virendra Bhandari, Anand Lodhi, Ashar Iqbal Lodi, Somya Sharma
Department of Radiation Oncology, Sri Aurobindo Medical Collage and P.G Institute, Indore-Ujjain highway, Indore, India
|Date of Submission||22-Jan-2022|
|Date of Decision||14-Mar-2022|
|Date of Acceptance||18-Mar-2022|
|Date of Web Publication||30-Jan-2023|
Department of Radiation Oncology, Sri Aurobindo Medical Collage and P.G Institute, MR 10 Crossing, Indore-Ujjain highway, Indore
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Pituitary Carcinoma is a rare neoplasm and presentation in paediatric age group is even rarer (1:1,000,000). In contrast to pituitary adenomas, pituitary carcinomas are more commonly non-functioning. Furthermore, due to the lack of specific markers, the diagnosis of pituitary carcinoma remains difficult prior to demonstration of metastasis. In view of the rarity of this disease, treatment is often difficult to plan. We present a case of seven years age old female who presented with left eye ptosis associated with squint, double vision and headache. Magnetic Resonance Imaging (MRI) Brain revealed large mass lesion in region of sella extending into suprasellar cistern and left parasellar region suggestive of Pituitary Macroadenoma. She underwent partial excision of tumour under neuro navigation. Histopathology suggestive of pituitary lesion with atypical feature. Block review showed pituitary carcinoma. We present here the details of this rare tumour.
Keywords: Aediatric, macroadenoma, pituitary carcinoma
| Introduction|| |
Pituitary carcinoma is primary adeno-hypophysial neoplasm with craniospinal and/or systemic metastases. Pituitary carcinoma is very rare and is only diagnosed when pituitary tumor noncontiguous with the sellar region is demonstrated. Diagnosis is difficult, resulting in delays that may adversely effect outcome that is traditionally poor. Pituitary tumour in paediatric age group are almost never malignant and hormonal secretion is also rare.Pituitary adenomas accounts for 10% to 25% of all intracranial neoplasm. Depending upon biological functioning Adenoma are benign, invasive and carcinoma. Adenoma 10 mm or more in size are defined as Macroadenoma while smaller than 10 mm defined as microadenoma. Pituitary carcinoma accounts for 0.1 to 0.2% of all adenomas making it rarest.,, Since local mass effect is most common mode of presentation, surgery is preliminary indication of treatment followed with adjuvant local Radiotherapy.
| Case History|| |
We present a case of seven year old female with initial complaints of left eye ptosis, squint associated with double vision since nine months. MRI Brain revealed mass lesion of size 3.3 × 4.6 × 2.7 cm suggesting possibility of invasive pituitary macroadenoma for which she underwent partial tumor excision under neuro navigation. Post Operative histopathology report was suggestive of pituitary lesion with atypical feature. Block review suggestive of Pituitary carcinoma. Immunohistochemistry (IHC) markers showed positive synaptophysin, ki 67 proliferating index 70% confirming pituitary carcinoma.
| Diagnostic Imaging|| |
MRI Brain revealed mass lesion of size 3.3 × 4.6 × 2.7 cm in region of sella extending into suprasellar cistern and left parasellar region along dorsal aspect of clivus associated with enlargement and erosion of dorsum sellae along posterior clinoid process and floor with effacement and abutment along floor of third ventricle, also abutting on with displacement of adjacent brain parenchyma of left temporal lobe [Figure 1].
|Figure 1: Pre OP MR Brain Navigation Protocol showing characterstic large defined extraaxial mass lesion extending into left perasellar region also linear extension along dorsal aspect of clivus on left side associated with enlargement of the sella with erosion of floor of sella|
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She then Underwent Left frontotemporal craniotomy and partial excision of tumour.
Pathological finding and molecular finding: Block review: tumour composed of round to oval cells having high nucleus to cytoplasm ratio, hyperchromatic to vesicle nuclei with prominent nucleoli and eosinophilic cytoplasm, forming sheath, lobules, and few acini. Tumour giant cell, area of necrosis seen focal area shows oncocytic type of cell with eosinophilic cytoplasm, stroma shows fibrosis, focal area of myxoid change. Few mitotic figures seen. Feature suggestive of Pituitary carcinoma [Figure 2].
|Figure 2: Histopathological examination showing round to oval cell with prominent nucleoli, forming sheath, lobules and few acini. Tumour giant cells, area of necrosis are seen (40x)|
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Immunohistochemistry report: Cytokeratin(CK) 7 Negative, CK 20 negative, Glial Fibrillary Acidic Protein (GFAP) negative, positive synaptophysin, Ki 67 proliferating index 70%, Intesnsity +++ [Figure 3].
|Figure 3: Immunohistochemistry in pituitary carcinoma for Ki 67 proliferating index 70%, Synaptophysin positive|
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Post operative Computed Tomography brain imaging revealed residual soft tissue density mass lesion in sellar and suprasellar cistern extending into left parasellar lesion with associated erosion of posterior clinoid process and dorsum sellae abutting adjacent neuroparenchyma involving left temporal lobe [Figure 4].
|Figure 4: Post OP CT Brain-Transverse and coronal section showing Residual heterogeneously hyperdense soft tissue density mass lesion in sellar and suprasellar cistern extending into left parasellar region with associated erosion of posterior clinoid process and dorsum sellae involving left temporal lobe|
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Patient planned for Radiation with 50.4Gy in 28 fractions with 1.8Gy per fraction to residual disease and post operative bed.
| Discussion|| |
Pituitary adenoma are benign tumor that arise from pituitary gland. It accounts for 10–15% of all intracranial mass lesion, and are relatively common. Tiny microscopic pituitary adenoma arefound in one in five adults but most of them remains asymptomatic. Most of the cases were diagnosed at autopsy and accounts for 0.1% to 0.2% of all pituitary tumours. It can appear at any age but most common age presentation is third to fifth decade with pre-excisting adenoma. Many pituitary tumors that will ultimately become carcinomas declare their aggressive behavior early and are unresponsive to standard therapy from the outset and/or recur quickly after surgical debulking and progress rapidly to carcinoma. However, other tumors may initially be responsive to standard therapy for prolonged periods and only progress to carcinomas after many years. The latency period between the diagnosis of benign adenoma and its transformation into malignancy is 0.3 to 18 years as interval between initial diagnosis of adenoma and transformation to carcinoma(mean 6.6;median 5.0 year) as reported by Pernicone et-al. Typically non-functioning pituitary adenoma causes symptoms only when it abuts surrounding brain structure most commonly optic chiasma which manifests as visual field defect and vision loss. Pituitary adenoma primarily is classified as per size of the mass,size smaller than 10 mm are microadenoma. Whereas macroadenoma by definition are more than 10 mm diameter. Pituitary Adenoma pathogenesis is unknown, most adenoma are sporadic, rarely genetically caused.Hereditary cases of pituitary adenoma represent 5% of all pituatory tumour. Mutation of following genes plays role in development of pituitary adenomas.
Multiple endocrine neoplasia type I: It is a tumour suppressor gene with loss of function mutation which leads to tumour formation in the pancreatic, parathyroid and pituitary gland.
Multiple endocrine neoplasia type IV (MEN4): MEN 4 has a mutation in the cyclin-dependent kinase inhibitor 1 B gene (CDKN1B) presenting with hyper-parathyroidism, pituitary tumours, testicular, and cervical neuroendocrine tumours.
Carney complex (CNC): which is germline mutation of the tumour suppressor gene PRKAR1A which leads to pigmented nodular adrenocortical (PPNAD), thyroid nodules, testicular tumours, spotty skin hyperpigmentation, and acromegaly.
This patient presented with Left eye ptosis since nine months and headache since five days. While most common symptoms in adult are amenorrhea, galactorrhea, weight gain and obesity. MR Brain navigation protocol of this patient shows mass lesion of 3.3 × 4.6 × 2.7 cm seen in the region of sella extending into suprasellar cistern and left parasellar region, associated with erosion of dorsum sellae along posterior clinoid process and floor of the sella, associated with elevation of optic chiasma, closely abutting on adjoining optic tracts, displacement of adjacent brain parenchyma of left temporal lobe. The hormone profile initially at the time of diagnosis suggestive of hypopituitarism, hypothyroidism, adrenal insufficiency and hyperprolactenemia. Pituitary carcinomas tend to disseminate systemically via lymphatic and hematogenous spread rather than via craniospinal spread, with a reported frequency of 47% systemic metastases, 40% craniospinal metastases, and 13% exhibiting both.,, Surgical procedures are very rarely curative due local invasion in the surrounding area. Surgery is basically to relieve the compressive symptoms. Transphenoidal resection is generally done for debulking to relive compressive symptoms. Here the patient underwent Left frontotemporal craniotomy and partial excision of tumour as per the treating surgeon’s discretion. Post surgery hormone profile suggest hypothyroidism, hypopituitarism, pituitary growth hormone deficiency and hence started on hormonal therapy. Radiation is used to control growth and spread of disease by preventing regrowth of tumor in large or partially excised mass. 45–55 Gy dose has been recommended for the primary tumour, Whole Brain Radiotherapy (WBRT) for brain metastasis, and stereotactic radiosurgery for small isolated lesion. Here she has been planned for 50.4Gy in 28fractionswith 1.8Gy per fraction. There is no significant in change in rates of Radiation therapy in young adult and elderly.There is no standardized protocol for chemotherapy. Various treatment combinations including Temozolamide(TMZ), cisplatin, carboplatin, etoposide, procarbazine, dacarbazine, paclitaxel, vincristine, methotrexate, cyclophosphamide and doxorubicin. TMZ has been widely used and effective. TMZ along with Radiation may be used. TMZ is utilized as a radio-sensitizing agent along with EBRT followed by TMZ as a monotherapy.
Pituitary carcinomas are generally associated with a poor prognosis despite administration of maximal multimodal therapies. Patients with systemic metastases have a median survival of 12 months, whereas those with metastases confined to the central nervous system live longer with an average of 2.6 yr.,,,
| Conclusion|| |
Pituitary carcinoma is rare in adults but may be observed in paediatric age group also, although very rare. Rapid diagnosis leads to timely and appropriate medical and surgical treatment and decreasing the morbidity and mortality risks. The survival remains poor even after complete treatment.
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Conflicts of interest
There are no conflicts of interest.
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