Malignant Pheochromocytoma: about Two New Cases  

Ali El Mahdi Haddam2 , Soumeya Nora Fedala1 , Farida Chentli2 , Djamila Meskine2
1. Department of endocrinology bab el oued hospital, Algeria
2. Department of endocrinology bologhine hospital, Algeria
Author    Correspondence author
International Journal of Clinical Case Reports, 2015, Vol. 5, No. 31   doi: 10.5376/ijccr.2015.05.0031
Received: 28 Apr., 2015    Accepted: 13 Jul., 2015    Published: 23 Jul., 2015
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Ali El Mahdi Haddam, Soumeya Nora Fedala, Farida Chentli, Djamila Meskine, 2015, Malignant Pheochromocytoma: about Two New Cases, International Journal of Clinical Case Reports, 5(31) 1-5 (doi: 10.5376/ijccr.2015.05.0031)


Malignant pheochromocytomas are very rare tumors characterized by high morbidity and mortality and therapeutic difficulties.

We report observations of a man and a woman who presented malignant pheochromocytoma discovered during the exploration of malignant hypertension. Laboratory tests confirmed the secretory nature of the mass. Malignancy was affirmed by the existence of hepatic and bone metastases during the initial radiological investigation in a case and during evolution in the other case.

Malignant pheochromocytoma; Adrenergic signs; MIBG; Magnetic resonance; Adrenalectomy

Malignant pheochromocytomas are tumors, developed at the adrenal medulla and paraganglia. Their diagnosis is made by the presence of metastases in organs devoid of chromaffin tissue or by the appearance of neoplastic recurrence (Lenders et al., 2005). They are characterized by constantly high morbidity and mortality due to the effects of uncontrolled and important cathecolaminergic hyper secretion and resistance to conventional cancer treatments (Pacak et al., 2001)

The objective of this study is to report the observations of two cases followed in our department
Observation 1
AM aged 30 years old was admitted for suspiscion pheochromocytoma. The beginning of symptoms was a year ago marked by the development of severe hypertension associated with significant adrenergic signs made of palpitations, sweating and paroxysmal headache. The patient is put under antihypertensive treatment without etiological exploration. It is only in front of the onset of abdominal pain that abdominopelvic ultrasound is made revealing a large heterogeneous mass in the adrenal.
Physical examination on admission revealed a weakness patient, thinner (BMI 16 kg/m2) having a malignant hypertension (Average of systolic and diastolic pression respectfully 260 mmHg and 160 mmHg) despite a hypotensive triple therapy. The physical exam did not find palpable mass, but spontaneous pain and caused by palpation of the right flank. The rest of the physical exam was unremarkable.
The hormonal exploration showed very high levels of metanephrine: 16 mg/24 hour (N <1) and CT + MRI adrenal showed a voluminous heterogeneous mass of 80x50 mm containing a dense necrotic area partially enhanced after iodinated injection what characterized pheochromocytoma (Figure 1).

Figure 1 Voluminous right adrenal mass taking heterogeneously the contrast medium

The patient is laparotomy operated. Total adrenalectomy is performed
Postoperative revaluation showed a disappearance of the adrenergic hyper secretion. Three months later, we noted the reappearance of symptoms evidenced by the new increase rate methoxylated derivative (10 mg / 24 hour). CT scan showed a tumor recurrence 13x15 mm infiltrating the upper pole of the kidney with the presence of lymph nodes deep retrocaval and inter aorto cellar of 20 and 25 mm intensely enhanced after contrast (Figure 2 and 3).Surgical revision allowed the removal of metastatic lymph nodes. However, surgical excision was incomplete at the adrenal mass due to local invasion. Treatment with MIBG labeled therapeutic dose allowed a 50% reduction in tumor volume. The patient has been oriented secondarily in oncology for adjuvant chemotherapy. The latest controls showed a significant reduction in metanephrine 2,2mg / 24 hours with a well balanced blood préssion on monotherapy.

Figure 2 Presence of precave and interaorticocave lymph nodes (23 and 29 mm)

Figure 3 Residual tumor 13x15mm weakly enhancedafter injection of medium contrast

Observation 2
TH aged of 28 years old was admitted for suspiscion right pheochromocytoma. Questioning revealed that the symptoms appeared three monthsbefore by the development of malignant hypertension (mean systolic and diastolic pression respectfully 200mmHg and 140mmHg) adrenergic signs associated with weight loss in a context of asthenia and abdominal pain. The hormonal exploration carried showed a significant rise in interest rate derivatives methoxylated: 18 mg/24 hours. Examination on admission revealed an astheniapatient complaining of pain in the right flank. Physical examination revealed a large palpable abdominal mass associated with hepatomegaly. Imaging CT scan showed a large and heterogeneous adrenal mass 120x80mm partially necrotic invading the inferior vena cava and liver (Figure 4).

Figure 4 Voluminous right adrenal mass

The staging showed multiple other lung and bone lesions (Fig
ure 5 and 6). Partial resection of the adrenal mass has improved the clinical picture by reducing adrenergic hyper secretion.

Figure 5 Multiple osseous metastases

The patient is then directed for a cure of chemotherapy and MIBG therapeutic dose. Infortunetly, she died of pulmonary embolism during chemotherapy.
Pheochromocytomas constituting a very rare cause of hypertension. Their prevalence in hypertensive patients is estimated between 0.1 and 0.6% (Lenders et al., 2005). However, it is important to make the diagnosis early because of a surgical cure in 90% of cases and a spontaneous fatal evolution due to significant hemodynamic repercussions (Eisenhofer et al., 2003).
Malignant pheochromocytoma is even rarer. It represents about 10% of cases. Its diagnosis is difficult because there are no histological criteria of certainty. Only a local recurrence and metastases or thepresence of chromaffin tissue in organs usually devoid of can confirm the diagnosis (Deutschbein et al., 2011; Kerkhofs et al., 2015).
The clinical presentations are varied and depend on the secretory profile. Tumors secreting norepinephrine mainly cause vasoconstriction and diastolic hypertension. When the adrenaline is predominant, we observe tachycardia, systolic hypertension with orthostatic hypotension and risk of major hypotensive access, or non-cardiogenic pulmonary edema. If preferential or exclusive secretion of dopamine, there is usually no arterial hypertension and the diagnosis is often suspected in atypical manifestations or fortuitous discovery of an adrenal mass (Bravo, 2004)
On the clinical level, the most common mode is revealing the sudden onset of hypertension, classically severe, unstable, see malignancy associated with the characteristic triad of Menard (headaches, palpitations, sweating) with an anxiety and weight loss. Paucysymptomatic or atypical picture can observe and delay diagnosis (Cheikhrouhou et al., 2006).Cardiovascular manifestations can be very serious and cause serious injury: acute pulmonary edema, myocardial infarction and subarachnoid hemorrhage. The impact assessment reveals hypertrophy, left ventricular dilatation and ophthalmologic complications (Mishra et al., 2000; Lehnert et al., 2004).
The diagnosis of pheochromocytoma is based on blood and urine bioassay catecholamine and metanephrine. A very important hypersecretion adrenergic often characterizes malignant pheochromocytoma. Dopamine secretion is strongly predictive of neoplasia (Lenders et al., 2002; Kudva et al., 2003.
When there's no evidence of malignancy, patients must be long term follow up because of metastases may occur many years later. Topographically, CT scanning can identify the tumor lesion, clarify its measurements and detect the presence of metastases. The magnetic resonance imaging allows characterization pheochromocytoma and has the advantage of determining its anatomical relationship with neighboring organs including the inferior vena cava (Plouin et al., 2000).
The therapeutic management is very difficult. It is based on surgical resection whenever possible including cases of metastases. Indeed partial surgery increases survival. In extensive and inoperable forms,therapeutic options are limited by the low sensitivity of tumor cells with chemotherapy and radiotherapy. Apart from symptomatic medical treatment of adrenergic hypersecretion by alpha blockers and beta blockers, MIBG labeled with iodine 131 is, at present, the main treatment option for fixing the tracer tumor sites (Goffredo et al., 2013; Goffredo et al., 2015).
The treatment is well tolerated except a mild transient hematologic toxicity. In three-quarters of the cases, a good therapeutic response is observed. The symptomatic response results in a reduction of blood pressure, improving the general condition and decreased pain. Objective tumor responses are rare (5%) but a partial tumor response was observed in 30% of cases and tumor stabilization, extended an average of 2 years in more than half of patients (Rutherford et al., 2014; Yoshinaga et al., 2014).
Arterial embolization selective tumor masses and radio chemotherapy for bone metastases remain palliative treatment (Deutschbein, 2015).
Malignancy pheochromocytoma is defined only by the existence of metastasis or recurrence of neoplastic. The clinical picture is often severe. Surgery of malignant pheochromocytoma, even at the stage metastatic must be done because it increases survival. Chemo radiotherapy and MIBG constitute an important part of the therapeutic arsenal and should be considered secondary. The management of these patients requires a multidisciplinary collaboration involving endocrinologists, surgeons, oncologists, nuclear physicians and pathologists. The prognosis remains pejorative.
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