Thankamma Ajithkumar
Case history
An 80-year-old woman presented with a rapidly growing lesion on her left cheek. She had first noticed this lesion 8 months previously, and it was slowly growing until her presentation. She underwent excision of the lesion, and the histopathology showed a 2.5cm infiltrating tumour mass composed of monomorphic small round blue cells with little visible cytoplasm. Numerous mitotic figures were seen, and the cells stained positive for CD20 and negative for TTF-1 and CD7.
Question
1. What is your diagnosis?
Answer
1. What is your diagnosis?
The combination of CD20 positivity and TTF-1 negativity suggests that the tumour is a Merkel cell carcinoma (MCC). MCC is a neuroendocrine tumour of the skin, characterized by a perinuclear punctuate or dot-like pattern of CD20 staining. Differential diagnosis of a small round cell neoplasm of the skin includes metastatic small cell lung cancer (SCLC), MCC, lymphoma, and melanoma. The use of a selective panel of immunohistochemistry tests helps to make a definitive diagnosis (Table 22.1).
Table 22.1 Immunohistochemistry in small round cell neoplasms of the skin
Shortly after the initial excision, the lesion recurred; she therefore underwent further surgery which showed similar cancer with invasion of deep muscles and a close excision margin.
When she attended the oncology clinic 4 months later, she had developed another nodule of 1.5cm near the edge of the previous skin graft.
Question
2. How would you proceed?
Answer
2. How would you proceed?
Further evaluation requires a detailed history including significant comorbidities and a clinical examination to delineate the local disease and identify any enlarged regional nodes. Since MCC has a high risk of both regional nodal and distant metastasis, she needs staging with CT/MRI of the head and neck and a CT scan of the chest and abdomen. Some authorities also recommend 18FDG-PET scan in patients with regional nodal metastases. The role of 68Ga-DOTATOC PET is being investigated.
CT staging showed no regional nodal disease or metastatic disease.
Questions
3. Outline your further management.
4. Should you consider systemic treatment for her, and if so why?
5. What is the role of primary radiotherapy in MCC?
Answers
3. Outline your further management.
She is recommended to have radical radiotherapy to the loco-regional area. Without radiotherapy, after wide excision of tumour, >40% patients develop local recurrence and >80% develop regional recurrence (this woman had two successive local recurrences within a short period of time). Therefore adjuvant radiotherapy to a dose of 50–56Gy is recommended.
Optimal management of clinically node negative disease is uncertain. Studies show that the risk of nodal disease correlates with size of the primary tumour. Patients with a primary tumour of >1cm have a >30% risk of nodal involvement. Sentinel node biopsy is helpful in deciding the need for regional nodal treatment. Patients with negative sentinel node biopsy do not need any nodal treatment, whereas those with positive nodes are treated with radical radiotherapy or complete nodal dissection, followed by adjuvant nodal radiotherapy if there is extracapsular extension or advanced nodal disease. Patients who have not had a sentinel node biopsy or lymphadenectomy are recommended to have regional nodal radiotherapy to a dose of 45–50Gy.
This patient is recommended to have radiotherapy to the primary tumour, parotid bed, and ipsilateral cervical nodes (because of unknown nodal status).
4. Would you advise adjuvant chemotherapy for her?
The benefit of adjuvant chemotherapy in MCC is controversial and therefore not advised outside clinical trial settings.
5. What is the role of primary radiotherapy in MCC?
Primary radiotherapy is an acceptable option when surgery is not technically feasible or the patient is medically unfit for surgery. A dose of ≥60Gy is recommended and gives a 75% in-field control rate.
She received 60Gy in 30 fractions to left side of the cheek, left parotid, and upper neck and 50Gy in 25 fractions to the left lower neck. One year after completion of radiotherapy she presented with two subcutaneous nodules over the anterior chest wall just above the costal margin. Excision showed MCC. Her ECOG performance status was 0. Figure 22.1 shows the re-staging CT scans.
Fig. 22.1
Questions
6. What does the imaging in Fig. 22.1 show?
7. What is your management at this stage?
8. What is her prognosis?
Answers
6. What does the imaging in Fig. 22.1 show?
There is a soft-tissue mass (3.2cm) between the upper pole of the left kidney and the diaphragm (A). Another mass is seen posterior to the right lobe of the liver (1.4cm) (B). The scan also showed a pancreatic lesion and multiple lung and pleural nodules (not shown here).
7. What is your management at this stage?
Combination chemotherapy is the standard treatment for distant metastatic disease. Radiotherapy has a role in symptom relief. Patients with a solitary metastasis may be considered for surgery, though there is a paucity of evidence concerning this approach.
Because of the similarities between MCC and SCLC the chemotherapeutic approach is same as that for SCLC. The regimen of cisplatin/etoposide yields a response rate of 60% with a 36% complete response in MCC whereas cyclophosphamide, doxorubicin, and vincristine (CAV) produces a 70% response rate with a complete response of 35%. The average duration of response is 8 months. Complete responders may have a better duration of response (20 months) than those with a partial response (3 months).
8. What is her prognosis?
Median survival of patients with metastatic MCC is 8–12 months, with a 5-year survival of 25%.
After four courses of a carboplatin/etoposide regimen, she achieved a complete radiological response. Six months later she presented with right shoulder pain, and a re-staging CT scan was done (Fig. 22.2).
Fig. 22.2
Questions
9. What does the scan in Fig. 22.2 show?
10. What is your management now?
Answers
9. What does the scan in Fig. 22.2 show?
The CT scan shows a soft tissue mass arising posterior to the right glenoid, extending into the posterior chest.
10. What is your management now?
Since she has pain from the locally advanced tumour, she might benefit from palliative radiotherapy. The radiotherapy dose ranges from 8–10Gy as one fraction to 20–30Gy in five to ten fractions.
If her ECOG performance status remains good (0–1), she may be offered further systemic treatment. Despite a high initial response rate, relapses are frequent after platinum/etoposide for MCC and SCLC. Patients are classified as sensitive to treatment if recurrence occurs ≥90 days after the end of first-line treatment or resistant if disease recurs within 90 days. Patients who progress during first-line treatment are classified as refractory. Sensitive patients may be re-challenged with first-line treatment, though there are no randomized trial data regarding this approach. Topotecan is the only approved second-line treatment independent of time of progression, and results in an OS 84 days longer than the best supportive care.
Progress and follow-up
She was re-challenged with carboplatin/etoposide for four courses, which yielded only a partial response. She died 3 months later, 33 months after her first presentation.
Further reading
Becker JC. Merkel cell carcinoma. Annals of Oncology 2010; 21(Suppl 7): vii81–vii85.
Gonzalez RJ, Padhya TA, Cherpelis BS, et al. The surgical management of primary and metastatic Merkel cell carcinoma. Current Problems in Cancer 2010; 34: 77–96.
Kudchadkar R, Deconti R. Systemic treatments for Merkel cell carcinoma. Current Problems in Cancer 2010; 34: 97–107.
Rao NG. Review of the role of radiation therapy in the management of Merkel cell carcinoma. Current Problems in Cancer 2010; 34: 108–117.
Schrama D, Ugurel S, Becker JC. Merkel cell carcinoma: recent insights and new treatment options. Current Opinion in Oncology 2012; 24: 141–149.