OBSERVATION

A 24 years old woman, housewife, was hospitalized in the Pulmonary Department in November 2009 for haemoptysis of medium abundance with anemia. She has as main medical history a melanoma of the scalp diagnosed at the age of 13 treated by surgery and chemotherapy with frequent relapses requiring repeated treatment. Clinical examination at admission found a patient in good hemodynamic state (TAS = 140 mmHg, TAD = 90 mmHg, accelerated pulse at 95 b / min). The plumonary examination revealed a respiratory rate at 19 c /min and crackling rales at the right pulmonary "eld. !e rest of the clinical examination was without abnormalities apart from the scars of bilateral cervical lymph node dissection. Biologic examination showed, microcytic normochromic anemia at 9.4 g / dl, correct renal function. Arterial gases was in favor of hyperventilation respiratory alkalosis (PH: 7.59, PaCO2: 21 mmHg, PaO2: 92 mmHg, HCO3: 20 mmol / l, SatO2: 96%). The chest x-ray (Figure 1) showed an alveolar infiltrate of the right upper lobe associated with multiple nodular lesions occupying the right pulmonary and left basal regions.

Thoracic Chest Tomography (CT) (Figures 2-3) showed parenchymal condensation in the ventral segment of the right upper lobe with multiple nodular lesions with confluent contours.

The patient was initially treated with hemostatic treatment and an immediate evolution has been marked by the worsening after 2 days and the haemoptysis became of great abundance causing a deglobulinization of 3.5 g / dl (the hemoglobin decreased from 9.4 g / dl to 5.8 g / dl) with clinical signs of bad tolerance of anemia with signs of acute respiratory failure. !e patient was then transferred to the intensive care unit where she was transfused with reinforcement of the hemostatic treatment. 

Bronchial fibroscopy visualized a diffuse bleeding of the whole bronchial tree more marked in the ventral segmental of the upper right lobe, an aspect evoking an intra-alveolar haemorrhage.

Bronchoalveolar lavage (BAL) in serial lavages was hemorrhagic with a macrophage predominance formed by 100% of siderophages in the cytological study. In the presence of this IAH and taking into account the patient’s life-threatening risk, treatment with intraveinous bolus of corticosteroids (Methylprednisolone 500mg per day for 3 consecutive days) was initiated with oral corticosteroids at 1 mg / kg / day. The evolution was rapidly favorable with drying up of the bleeding and complete cleaning of the alveolar and nodular lesions as well on the chest X-ray and thoracic CT in a few days (Figures 4-5)

After stabilization of the patient’s clinical state, an etiological investigation was initiated, the immunological assessment (antinuclear antibody, ANCA, rheumatoid factor) was normal, 24 hour proteinuria was negative, bronchial bacteriological and parasitological examinations and tumor markers (ACE, CA 15- 3, CA 125, KHCG, CA 19-9) were normal.After a negative etiological investigation and especially the reappearance of nodular lesions on the CT scan at 6 months of corticosteroid treatment, a pulmonary biopsy was performed which revealed a histological and immunohistochemical aspect compatible with a pulmonary metastasis of achromic melanoma fusiform cells with multifocal positivity with HMB-45, melan A is negative. (Figure 4)

The patient was therefore diagnosed with a neoplastic HIA revealing pulmonary metastases of a melanoma of the scalp. Second line chemotherapy was indicated but formally refused by the patient. Corticosteroids were maintained at a maintenance dose of 20mg per day of Prednisone. The patient died following haemoptysis after one year of follow-up.

DISCUSSION

Intra-alveolar haemorrhage(IAH) is associated with multiple immunological and non-immunological etiologies. The neoplastic origin is a very rare cause. It has been described in the literature as reported cases, butthe mechanism involved is not well defined. [2] The neoplastic IAH has been associated with certain types of cancer including pulmonary Kaposi sarcoma. Table I presents the various cases published in the literature

The IAH revealed the underlying neoplasia in most cases reported. [5-15] To our knowledge, our observation represents the first described case of HIA revealing pulmonary metastases of a malignant melanoma. 

Two hypotheses are possible to explain the mechanisms of this IAH in our patient, 

• Either the presence of vascular tumor emboli that would result in tumor invasion and pulmonary vascular destruction. However, data from the anatomopathological examination of the pulmonary biopsy exclude this hypothesis since they have shown the presence of fusocellular tumor proliferation with high mitotic activity in the absence of endovascular neoplastic emboli.
• Or it must be the existence of a neaoplastic autoimmune phenomenon linked to the melanocytic tumor cells. This hypothesis is more plausible since the initial development under general corticosteroid therapy was rapidly favorable.

Many observations suggest that human malignant melanoma expresses antigens that can induce a beneficial immunological reaction which has opened a new therapeutic pathway to immunotherapy in malignant melanoma. [16] The favorable progression under corticosteroid therapy was also observed in a case reported by Rajdev et col about a primary hemangiosarcoma of the metastatic heart associated with intra-alveolar hemorrhage and presumed of the immunological mechanism. [17] 

This hypothesis was also advanced in some cases of myelodysplastic syndromes where there is a satellite vasculitis of the haematological process. [18]

CONCLUSION 

Our observation corresponds to the first reported case of IAH due to pulmonary metastases of a melanoma of the scalp. The susceptibility of human malignant melanoma to express antigens that can induce an immune reaction and the initial rapid favorable evolution to corticosteroid therapy in our patient argue in favor of the immunological origin of this neoplastic IAH.

CONFLICT OF INTEREST

The authors stated that they have no potential conflicts of interest in relation to the theme of the article.