Lack of Correlations among Histopathological Parameters, Ki-67 Proliferation Index and Prognosis in Pheochromocytoma Patients

Ocal, Irfan; Avcı, Arzu; Çakalağaoğlu, Fulya; Can, Hüseyin

doi:10.7314/apjcp.2014.15.4.1751

Cited by 10 publications

(13 citation statements)

References 13 publications

(35 reference statements)

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“…The PASS was not originally developed for PGLs and, therefore, there is some uncertainty in applying the components of the PASS to these tumours. The clinical features and histopathological characteristics are, however, similar for PCCs and PGLs (31).…”

Section: Discussionmentioning

confidence: 89%

Genotype–phenotype associations in PPGLs in 59 patients with variants in SDHX genes

Main

Rossing

Borgwardt

et al. 2020

Endocrine Connections

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Phaeochromocytomas and paragangliomas (PPGLs) are tumours of the adrenal medulla and extra-adrenal sympathetic nervous system which often secrete catecholamines. Variants of the SDHX (SDHA, -AF2, -B, -C, -D) genes are a frequent cause of familial PPGLs. In this study from a single tertiary centre we aimed to characterize the genotype-phenotype associations in patients diagnosed with germline variants in SDHX genes. We also assessed whether systematic screening of family members resulted in earlier detection of tumours. The study cohort comprised all individuals (n=59) diagnosed with a rare variant in SDHX during a thirteen-year period. Patient- and pathology records were checked for clinical characteristics and histopathological findings. We found distinct differences in the clinical and histopathological characteristics between genetic variants in SDHB. We identified two SDHB variants with distinct phenotypical patterns. Family screening for SDHB variants resulted in earlier detection of tumours in two families. Patients with SDHA, SDHC and SDHD variants also had malignant phenotypes, underlining the necessity for a broad genetic screening of the proband. Our study corroborates previous findings of poor prognostic markers and found that the genetic variants and clinical phenotype are linked and therefore useful in the decision of clinical follow-up. Regular tumour screening of carriers of pathogenic variants may lead to an earlier diagnosis and expected better prognosis. The development of a combined algorithm with clinical, genetic, morphological, and biochemical factors may be the future for improved clinical risk stratification, and forming a basis for larger multi-centre follow up studies.

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Section: Discussionmentioning

confidence: 89%

Genotype–phenotype associations in PPGLs in 59 patients with variants in SDHX genes

Main

Rossing

Borgwardt

et al. 2020

Endocrine Connections

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“…By contrast, our case of benign pheochromocytoma showed an extremely high level of cell proliferation potential, with a PI of 9.7 %. The relationships between cell proliferation and pathological characteristics including hormone secretion, tumor size, and symptoms in benign pheochromocytoma are not fully understood, although PI was reported to be significantly associated with capsule invasion of pheochromocytoma [ 24 ]. The relationship between the aggressiveness of PMC and cell proliferation is unknown, as this is the first report on cell proliferation in PMC.…”

Section: Discussionmentioning

confidence: 99%

Pheochromocytoma multisystem crisis treated with emergency surgery: a case report and literature review

et al. 2015

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BackgroundPheochromocytoma is a neuroendocrine tumor that predominantly presents with hypertension, palpitations, and tachycardia due to excessive catecholamine excretion. Although pheochromocytoma multisystem crisis (PMC) is relatively rare, urologists and clinicians should focus on early diagnosis as delay in initiating the appropriate treatment can lead to mortalityCase presentationA 70-year-old man developed ileus after a few days of medication for hypertension. Computed tomography incidentally revealed a left adrenal mass. This finding together with his clinical course was compatible with pheochromocytoma. An α-blocker was administered immediately, and his blood pressure was well controlled. However, his general condition and laboratory data deteriorated rapidly, and the patient was diagnosed with PMC with lethal status. Thus, emergency adrenalectomy was performed without confirmation of catecholamine levels. From the resected specimen, his tumor was judged as pheochromocytoma. On immunohistochemical analysis, the proliferation index evaluated by Ki-67 staining was 9.7 %. This case report was approved by the Human Ethics Review Committee of the Nagasaki University Hospital.ConclusionThe present case of PMC was successfully treated with emergency surgery. The benign pheochromocytoma also presented with high cell proliferation potential, which may be a cause of the extreme aggressiveness of PMC.

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“…Although differences were not documented in dogs, in humans with pheochromocytoma it has been shown that capsular invasion is associated with higher proliferation rate of tumor cells based on Ki-67. 18 Also, there were no differences for PASS and the immunohistochemical markers between young and old dogs. It is interesting to note that for pheochromocytomas a better outcome has been previously shown in younger dogs, 11 while in the present investigation age was not different between survivors and non-survivors.…”

Section: Discussionmentioning

confidence: 83%

“…6 Similarly to PASS, also some of the listed immunohistochemical markers, such as Ki-67, p53, BCL-2 and c-erbB-2, have not been invariably associated with a malignant course in humans with pheochromocytoma. 7,18,21 Alternatively, the lack of association between PASS or immunohistochemical markers and survival is explained be the relatively low number of dogs included in this study; the limited number may have decreased the chance to detect significant differences. Finally, it is worth mentioning that in humans with pheochromocytoma an important outcome predictor is represented by the presence of distant metastasis or their development during follow-up; metastasis can occur 5 years, or longer, after surgery.…”

Section: Discussionmentioning

confidence: 97%

Pheochromocytoma in Dogs Undergoing Adrenalectomy

et al. 2018

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Pheochromocytoma is frequent in dogs and carries a guarded prognosis. Current histological criteria may not predict malignant behavior in dogs, similar to humans. In humans, characterization of tumors has been refined using the pheochromocytoma of the adrenal gland scaled score (PASS) and by immunohistochemistry. The study aim was to investigate PASS and immunohistochemical markers used in humans in 24 dogs with pheochromocytoma that underwent adrenalectomy. Dogs with pheochromocytomas were reviewed and tumors collected. Histological sections were evaluated to apply the PASS and were single-labeled for chromogranin A, Ki-67, COX-2, p53, BCL-2, c-erbB-2, vascular endothelial growth factor, and S100. Survival, age, and vascular and capsular invasion were compared for PASS and immunohistochemical markers; results of PASS were also compared for each marker. Associations between markers were tested. PASS and immunohistochemical markers did not differ for survival, age, and vascular and capsular invasion. Tumors showing BCL-2 expression in >50% cells had lower PASS than those with lower expression (PASS: 7 ± 2 vs 9 ± 2; P = .011). Tumors positive for S100 had higher PASS than those that were negative (PASS: 10 ± 2 vs 7 ± 2; P = .001). Results of the different markers were not associated. In conclusion, in the context of canine pheochromocytoma, PASS and the selected immunohistochemical markers are not associated with survival, age, or vascular or capsular invasion. The higher PASS in S100-positive tumors may indicate that pheochromocytomas developing morphologic changes acquire S100 expression. The significance of lower PASS in tumors with elevated BCL-2 expression is uncertain. Overall, the use of PASS and the present immunohistochemical markers may not be useful in dogs with pheochromocytoma.

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Lack of Correlations among Histopathological Parameters, Ki-67 Proliferation Index and Prognosis in Pheochromocytoma Patients

Cited by 10 publications

References 13 publications

Genotype–phenotype associations in PPGLs in 59 patients with variants in SDHX genes

Genotype–phenotype associations in PPGLs in 59 patients with variants in SDHX genes

Pheochromocytoma multisystem crisis treated with emergency surgery: a case report and literature review

Pheochromocytoma in Dogs Undergoing Adrenalectomy

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