Early detection of lymph node metastases by 7.5 MHz-ultrasound examination in a patient with primary malignant melanoma of the lung

ARTICLE

Malignant melanoma generally presents as a primary neoplasm of the skin. However, mucosal localizations, such as the oral cavity, esophagus, larynx or the anogenital mucosa are also known [1-4].

PMML, indeed, is a very rare tumor. About 25 cases have been reported in the literature, but not all of them fulfil the requested criteria. In particular an extrapulmonary origin of the tumor has to be excluded. We report a case of a patient with PMML and discuss the use of 7.5 MHz-ultrasound for early detection of lymph node metastases.

Case report

In June 1996 a 55-year-old white male presented with respiratory symptoms including a cough which had not improved under symptomatic treatment.

A chest x-ray was performed and a solitary, exophytically growing tumor in the left lower lobe was detected. Histopathological analysis of a tumor biopsy obtained by bronchoscopy revealed a malignant melanoma. Staging procedures included computed tomography of the abdomen, chest and head and were completely normal except for the solitary lung tumor. A pulmonary metastasis of malignant melanoma was considered, but there was no history or sign of a cutaneous, mucosal or ocular melanoma. Physical examination of the skin and mucous membranes did not reveal an extrapulmonary malignant melanoma and a lobectomy of the left lower lobe and a sleeve resection of the upper lobe bronchus was performed.

Histopathological analysis revealed a solid growth pattern of a darkly pigmented neoplasm. The tumor was submucosal and endobronchial with extension into the peribronchial soft tissue. Loosely epitheloid cells with large, roundish hyperchromatic nucleoli were noted as well as pleomorphism and increased mitotic activity. A few nested foci were found in the bronchial mucosa. Immunhistochemical analyses showed strong positivity for S-100, Vimentin and HMB45. Based on these histological and immunohistochemical findings the diagnosis of a PMML was established [5].

Because of postoperative bronchial bleeding, a re-thoracotomy and further pneumectomy in the patient's left lung was necessary. Histological analysis revealed no evidence of further tumor tissue.

At a follow-up visit in August 1997 a 7.5 MHz-ultrasound examination revealed two hypoechoic, roundish structures in the patient's left axilla which could not be detected by palpation. Together they presented with a size of 1.4 x 0.9 x 1.0 cm and were suspicious for metastases of malignant melanoma (Fig. 1). Computed tomography of the thorax supported the diagnosis and a lymph node dissection of the left axilla was performed. Histologically two metastases and one micrometastasis were found. There was no evidence for any other tumor manifestation and an adjuvant therapy with interferon alpha (IFN-alpha) (3 x 6 Mio IE per week) was initiated in October 1997.

In April 1998, 7.5 MHz-ultrasound examination again revealed a clinically undetectable echolucent mass (1.0 x 1.4 x 1.5 cm) in the patient's left axilla (Fig. 2). Staging by computed tomography again did not reveal any other metastases except the tumor in the left axilla and radical surgical resection was performed. Histological analysis again revealed metastases of malignant melanoma.

Adjuvant therapy with INF-alpha was continued with no evidence for tumor progression until December 1998.

Discussion

The patient presented with clinical symptoms similar to those of lung cancer. Based on radiological and pathological findings after complete tumor resection, the diagnosis of a PMML was established. PMML is a very rare neoplasm, accounting for only 0.01% of all lung tumors [6]. The diagnosis in our patient was in accordance with previously proposed criteria for diagnosis of PMML, including the following [7, 8]:

1. Junctional changes like "dropping off" or "nesting" of melanoma cells just beneath the bronchial epithelium,

2. Invasion of the bronchial epithelium by melanoma cells,

3. Malignant melanoma associated with these epithelial changes,

4. A solitary lung tumor,

5. No history of a cutaneous, mucous membrane or ocular melanoma,

6. Absence of any other detectable tumor at the time of diagnosis.

The most important factor to clearly establish the diagnosis of PMML is the identification of a bronchial intraepithelial component in association with an invasive component of the tumor [5]. These and all other above mentioned criteria were clearly given in the patient presented.

The histogenesis of PMML has not been completely understood. There exist several theories to explain the occurrence of PMML. One of them hypothesises that melanocytes exist throughout the body as cells of a dispersed neuroendocrine system. Normally, melanocytes migrate to the epidermis and the dermoepidermal junction of the skin, but due to mismigration, visceral organs can be reached during embryogenesis. This has been suggested for the esophagus and the larynx and may be the case in the lung, too [2, 3].

Another theory emphasizes that melanoma cells may derive from a pluripotent stem cell. This is supported by the observation of Cohen et al. of a malignant melanoma within a pulmonary blastoma [9].

The main histopathological differential diagnosis of PMML is a melanocytic carcinoid tumor, a melanotic paraganglioma, a melanotic schwannoma and a pulmonary metastasis of a malignant melanoma. These tumors can often be excluded by histopathological and immunohistochemical analyses on the background of the clinical history of the individual patient [5]. Yet, in our patient a second interpretation is possible. The bronchial tumor could have been a single metastasis developing from regional node metastasis of an unknown primary which was diagnosed with 11 months delay. This phenomenon is also known in the skin where sometimes cutaneous metastases display an adjacent intraepithelial component.

While optimal treatment modalities of a PMML are not clearly established, early detection of lymph node metastases is important for early initiation of further treatment. In this regard, 7.5 MHz-ultrasound examinations are the most helpful tool. With this noninvasive diagnostic method lymph node metastases can be detected as hypoechoic or echolucent, roundish structures down to a diameter of 0.3 cm [10]. Postinflammatory lymph nodes presenting as oval structures with a hyperechoic center and a hypoechoic peripheral zone can be differentiated in most cases (Fig. 3) [11, 12]. Early detection of suspicious lymph nodes leads to early initiation of surgical treatment which the patient probably benefits from. With repeated surgery and adjuvant therapy with INF-alpha, the patient presented has already survived for more than 31 months, while the median survival with PMML is only 14 months [6, 13-15].

Article accepted on 19/10/99

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