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Basal cell carcinoma metastatic to cervical lymph nodes and lungs

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Basal cell carcinoma metastatic to cervical lymph nodes and lungs
J Scott Boswell MD1, Marshall S Flam MD2, David N Tashjian MD2, Tai-Po Tschang MD
Dermatology Online Journal 12 (6): 9

1. Department of Internal Medicine, University of California San Francisco-Fresno, Fresno, CA. jboswell@fresno.ucsf.edu2. Saint Agnes Medical Center, Fresno, CA


Metastatic basal cell carcinoma (MBCC) of the skin is rare in occurrence and may initially elude proper diagnosis and management. We describe a case of MBCC to cervical lymph nodes, originally evaluated and treated surgically as metastatic thyroid carcinoma. After definitive diagnosis of MBCC was made, chemotherapy and concomitant radiation treatment were initiated; however, despite these measures, the patient then developed MBCC to the lung. Risk factors and current therapeutic modalities for MBCC are also discussed. In addition to the more commonly metastasizing carcinomas, metastases from a cutaneous basal cell carcinoma primary tumor should be considered when evaluating cervical lymph node metastases of an uncertain head and neck primary.

Basal cell carcinoma (BCC) is the most common human malignancy worldwide. Despite its high incidence, metastasis occurs only rarely, with rates ranging from 0.0028 to 0.5 percent of cases [1]. Since Beadles first reported metastatic basal cell carcinoma (MBCC) in 1894 [2], only approximately 300 cases have been reported in the world literature [1, 3 4, 5], making MBCC a difficult entity to characterize in terms of etiology, risk factors, and therapeutic options.

Furthermore, because of its rare occurrence, MBCC may be mistaken at initial presentation for metastatic disease from other primary tumors that are more prone to metastasize. We present a case of BCC metastatic to the lung, which initially presented as an enlarged cervical lymph node.

Clinical synopsis

A 58 year-old man presented to his otolaryngologist with a 3-month history of a painless lump in his right upper anterior neck. The past medical history revealed a remote history of testicular seminoma, for which he had received radiation treatment to his retroperitoneum and mediastinum 25 years earlier. He also had a history of multiple basal cell carcinomas (BCCs) of the head, neck, torso, and back, but otherwise showed no clinical suggestions of basal cell nevus syndrome. A total of 22 BCCs had been diagnosed by biopsy and excised in the previous 6 years, including a 0.5 cm lesion from his right posterior neck 3 years previously that upon excision demonstrated clear margins and no evidence of metatypical features, perineural, or perivascular invasion.

On physical examination, a 1-cm firm, nontender mass in the right anterior high jugular region was noted. No thyroid mass was palpated. A computed tomography (CT) scan of the neck showed an 8-10 mm nodule in the left lobe of the thyroid gland, with no dominant soft tissue neck masses. Fine needle aspiration (FNA) of the left thyroid nodule then revealed a cytological interpretation of papillary thyroid carcinoma. A positron emission tomography (PET) scan demonstrated no abnormal uptake in the neck or elsewhere, but in light of his remote history of radiation, a presumptive diagnosis was made of papillary carcinoma of the thyroid with lymph-node metastasis.

The patient then underwent a total thyroidectomy and right supraomohyoid neck dissection. Pathological examination of the excised thyroid gland demonstrated septal fibrosis and focal nodular hyperplasia with variably-sized follicles, but no evidence of carcinoma. Sections of the right superior neck lymph node excision and right anterior neck dissection showed metastatic carcinoma in two of the four lymph nodes excised. The carcinoma was characterized by irregularly shaped aggregates, nests and cords of basaloid cells with peripheral palisading and a variable intervening fibrotic stroma (Fig. 1). When compared with the patient's right neck BCC primary tumor excised 3 years earlier (Fig. 2), the histopathology was very similar.

Figure 1Figure 2

Panendoscopy was next performed to rule out a mucosal basaloid squamous cell carcinoma primary tumor. Biopsies of both right and left valleculae, piriform sinuses, and nasopharynx bilaterally proved negative. Six weeks of radiation therapy and chemotherapy (carboplatinum and docetaxel) were performed.

Figure 3

Four years after completing chemoradiation, the patient presented with an asymptomatic, small, hard nodule at the base of the right neck at the junction of the cervical and supraclavicular regions. A biopsy of this lymph node confirmed relapse of MBCC, which was now multifocal and demonstrated vascular and perineural invasion (Fig. 3).

A chest x-ray was negative, but a CT of the chest revealed multiple bilateral pulmonary nodules, the largest of which measured 1.5 cm. A PET scan then revealed uptake in the lung corresponding to the nodules identified on the chest CT scan. No uptake was seen in the neck or at other sites.

The patient was again treated with carboplatinum and docetaxel. Currently, the patient is receiving a combination of docitaxel and gemcitabine and is due for follow up CT scans in the near future. Since developing the initial cervical lymph node metastasis, the patient has been diagnosed and treated for 20 new primary BCCs, all located on the head, neck, or torso.


Criteria for diagnosing MBCC were first set forth by Lattes and Kessler in 1951 [6]. They are as follows: 1. The primary tumor must originate from the skin and not the mucosa. 2. Metastasis must be demonstrated in a lymph node or a site distant from the primary lesion and cannot be from direct extension. 3. The primary and metastatic tumors must show similar histopathology.

BCC may metastasize by either lymphatic or hematogenous routes, or by both. The median age at the first sign of metastasis has been reported as 59, with the interval from onset of primary tumor to the time of metastasis ranging from <1 to 45 years [4]. A review by von Domarus and Stevens demonstrated that 70 percent of MBCCs originate from primary BCCs of the head and neck region [4]. The most common site for metastasis is to regional lymph nodes, followed by lung, bone, and skin [7, 8].

A limited number of reviews have elucidated several possible risk factors for developing MBCC. Those risk factors generally accepted are summarized in Table 1. Several other risk factors such as specific subtypes of primary BCC, a metatypical pattern, and immunosuppression in affected patients have been proposed, but are of unclear validity. Currently, Epstein and colleagues are utilizing comparative genomic hybridization (CGH) on samples of MBCC (including samples from our patient) to determine the degree of genomic instability that might accompany BCCs that metastasize.

Table 1. Risk factors for metastatic basal cell carcinoma
  1. Size of tumor > 2 cm [3, 7, 9, 10]
  2. Location on head and neck [1, 4, 9, 11]
  3. Tumor recurrence refractory to treatment [1, 7, 12, 13]
  4. Previous of radiation therapy [1, 7]
  5. Multiple primary tumors [7, 14, 15]
  6. Increased depth of tumor [7]
  7. Invasion of perineural space and blood vessels [4]
  8. Fair skin [3]
  9. Male [3, 4]

Therapeutic options vary depending on the location and extent of MBCC, but generally consist of surgery, chemotherapy, radiation, or a combination of the three. In cases where complete surgical excision is not possible, chemotherapy is preferred, with cisplatinum being the most effective agent [17]. In our case, carboplatinum and docetaxel were chosen to limit neurotoxicity in our patient, who had a significant pre-existing neural hearing loss.

Radiation therapy may be administered postoperatively or concomitantly with chemotherapy. However, despite the limited data of its role in treating MBCC, it is sensible to employ radiation with concurrent chemotherapy in view of improved outcomes (local control and organ preservation) when used to treat mucosal squamous cell carcinomas of the head and neck region.

The prognosis for MBCC is generally poor. Von Domarus and Stevens [4] demonstrated a median survival time of 8 months after initial metastasis, although survival times of up to several years have also been reported [3, 16]. Our case encourages a greater awareness among physicians of the need for definitive diagnosis and treatment of MBCC. While a neck mass more typically represents a spread from a carcinoma that is more prone to metastasize, the clinician should bear in mind that MBCC should be included in the differential diagnosis, especially in a patient with a history of recurrent or multiple BCCs.

The authors have neither commercial associations nor other conflicts of interest in the publication of this manuscript.


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