Erratum

A Quttainah, A Thoma, S Salama. Clinical-pathological review of 14 cases of merkel cell carcinoma. Can J Plast Surg 2002;10(5):196–202.Merkel cell carcinoma (MCC) is a rare, primary, cutaneous, neuroendocrine skin tumour that occurs commonly in the head, neck or extremities of elderly white people. Fourteen cases of MCC in the Hamilton Regional Cancer Centre between 1992 and 2000 have been reviewed. Seven cases required a panel of immunohistochemical markers and two cases required electron microscopy for confirmation. Seven men and seven women were treated, and ranged from 67 to 96 years of age (mean 77.7 years). The primary tumour was located in the head and neck in seven patients (50%), in the extremities in four patients (29%) and on the trunk in two patients (14%). One patient had an unknown primary tumour location. Ten patients had stage Ia disease at presentation, three had stage Ib disease, and one presented with stage II disease. Primary treatment consisted of wide local excision in nine patients, wide local excision and radiotherapy in four patients and radiotherapy only in one patient. Seven patients had recurrence, five were disease free up to their most recent follow-up, one died of unrelated causes, and one was lost to follow-up after primary treatment. Of the seven patients with recurrence, two had local recurrence, two had lymph node recurrence and three developed metastases. Disease-free intervals were 69% and 50% for six-month and one-year follow-up, respectively. No difference in outcome was observed between stage Ia and Ib disease. The patient with stage II disease at presentation developed metastases. Longer duration of disease before presentation had a higher incidence of recurrence with distant metastases. Extremity lesions had the best prognosis associated with disease-free interval. Early management with excision and radiotherapy improved the disease-free interval.     

Merkel Cell Carcinoma Arising from the Subcutaneous Fat of the Arm with Intact Skin

BACKGROUND: Merkel cell carcinoma is a rare malignant neuroendocrine neoplasm characteristically arising from the dermis of sunlight-exposed skin. It rarely arises outside the skin. OBJECTIVE: We present a patient with primary Merkel cell carcinoma arising from subcutaneous fat, with no involvement of the overlying skin. We describe the clinical manifestations and magnetic resonance imaging (MRI) findings. METHODS: We report a 63-year-old woman with a primary lesion of Merkel cell carcinoma that arose from the subcutaneous fat layer of the left arm. The lesion presented as a subcutaneous nodule with intact overlying skin. MRI showed that the nodular lesion was located entirely in the subcutaneous fat layer, with no involvement of the dermis. Peritumoral infiltration around the lesion and enlarged lymph nodes deep to the lesion were noted. The patient received wide excision of the lesion with dissection of the regional lymph nodes and adjuvant radiotherapy and chemotherapy. RESULTS: Histopathologic examination confirmed the diagnosis of Merkel cell carcinoma with local lymphatic metastasis, and the lesion was completely located in the subcutaneous fat, with no involvement of the dermis. These findings were well correlated with MRI findings. CONCLUSION: Primary Merkel cell carcinoma may arise from the subcutaneous fat and present as an entirely subcutaneous lesion with intact skin. MRI is helpful to evaluate the local extension of the lesion and regional lymphatic metastasis.     

Recurrence of a basal cell carcinoma in a skin graft in spite of total excision. A case report

The authors report an original case of a recurrence of basal cell carcinoma in a skin graft recipient site. The skin graft was used to resurface the defect following complete excision of basal cell carcinoma in the mandibular angle area. Three answers can be given to the question of the origin of that new carcinoma: recurrence of the primary carcinoma, metastasis to a lymph node or a transfer of a basal cell carcinoma located into the skin graft which grew further. This last hypothesis remains the most probable because the histology of the two carcinomas was different and that the patient presented many others locations of basal cell carcinomas. Skin grafted areas must be checked for recurrence of basal cell carcinoma in such patients because invisible basal cell carcinoma can be transferred within the graft where they can grow for their own.     

Approach to Metastatic Carcinoma of Unknown Primary in the Head and Neck: Squamous Cell Carcinoma and Beyond

Metastatic carcinoma to cervical lymph nodes presenting as an unknown primary is quite common. In most cases, the primary site is ultimately identified. Carcinomas that remain of unknown primary after a thorough search are uncommon. This review will focus on those cases that initially present as unknown primaries, since this is the setting in which pathologists first encounter these cases and in which they play an important role in guiding patient management. Most are squamous cell carcinomas, the majority of which are human papillomavirus (HPV)-related and originate in the palatine tonsils and base of tongue. HPV-related oropharyngeal squamous cell carcinomas are increasing in incidence and have unique clinical and pathologic features that make them particularly likely to present as an unknown primary. Understanding these features has led to improved detection of the primary tumors. Further, even when the primary tumor is not found, prognosis is very dependent on characterization of the tumor HPV status. Papillary thyroid carcinomas may also initially present without a known or clinically detectable primary, either as a neck mass or incidentally in a neck dissection performed for another indication. The latter is a very indolent disease. Finally, primary salivary gland carcinomas may mimic an unknown primary and need to be distinguished from cutaneous metastases to the parotid gland, which may present without a recognized skin tumor. Here, we review the clinical and pathologic features of these entities and provide a systematic approach to their diagnosis.     

Metastatic squamous cell carcinoma of the parotid: a case of an occult primary

Metastatic squamous cell carcinoma involving an intraparotid lymph node, although uncommon, remains of practical consideration in the differential diagnosis of a parotid mass. This is of particular importance when the primary skin lesion is not readily identifiable, or has been inadequately managed in the past. A representative case is presented, and a review of the literature follows with special emphasis on the anatomy of the parotid lymphatics and the implications for appropriate treatment.     

Oncologic rationale for bilateral tonsillectomy in head and neck squamous cell carcinoma of unknown primary source.

OBJECTIVE: To demonstrate an oncologic basis for the recommendation to perform bilateral tonsillectomy as a routine measure in the search for a primary mucosal lesion in patients presenting with cervical nodal metastasis of squamous cell carcinoma (SCC). STUDY DESIGN: A case series of individuals selected from a 3-year period is reported. SETTING: Academic medical center. RESULTS: Each individual presented with metastatic squamous cell carcinoma in a cervical lymph node from an unknown primary source. In each case, the primary source was identified in a tonsillectomy specimen, either located contralateral to the node, or in both tonsils. CONCLUSIONS: The rate of contralateral spread of metastatic cancer from occult tonsil lesions appears to approach 10%. For this reason, bilateral tonsillectomy is recommended as a routine step in the search for the occult primary in patients presenting with cervical metastasis of SCC and palatine tonsils intact.     

Metastatic Basal Cell Carcinoma Presenting as Unilateral Axillary Lymphadenopathy: Report of a Case and Review of the Literature

BACKGROUND: Although basal cell carcinoma (BCC) is one of the most common forms of cancer worldwide, the incidence of metastatic basal cell carcinoma (MBCC) is exceedingly low. Of reported cases, it is estimated that up to 85% arise in the head and neck region. OBJECTIVE: Case presentation of a BCC measuring 1.1 cm arising in a nonfacial site that presented with unilateral axillary lymphadenopathy. METHODS: Case presentation with literature review. RESULTS: Risk factors which should lead to a higher index of suspicion among clinicians for identifying these patients include large tumor size, previous irradiation, local invasion, and recurrence. The lymph nodes, lungs, bones, and skin are among the most common sites in which metastases arise. CONCLUSION: We report an unusual case of MBCC arising from a small, nonfacial primary BCC that presented with unilateral axillary lymphadenopathy.     

Extensive basal cell carcinoma on the right thoracic wall and its distant metastases

Basal cell carcinoma is the most common form of skin cancer, and it very rarely metastasizes. An aggressive case of basal cell carcinoma metastasizing to skin, lungs, posterior chest wall, liver and lymph nodes is presented here.     

Basal Cell Carcinoma Metastatic to Parotid Gland

Metastasis from basal cell carcinoma of the skin is very rare with cases being documented in the lymph nodes, lung, bone and parotid gland. The main histopathological differential diagnosis is the locally arising basal cell adenocarcinoma from which it is difficult to distinguish by morphology and routine immunohistochemistry. Approximately 85 % of all reported metastatic basal cell carcinomas arise in the head and neck region. Here we present a case of basal cell carcinoma of the skin of the left lateral canthus of the eye which metastasized to the intraparotid lymph nodes with infiltration of the adjacent parotid parenchyma. More awareness and vigilance is required on the part of the reporting pathologist to consider metastasis in the presence of a parotid tumour. Features favouring metastasis include history of primary cutaneous basal cell carcinoma, histological similarity to the primary lesion and absence of any demonstrable direct extension from the skin lesion. We also review the literature on metastatic basal cell carcinoma and discuss the need for adequate follow up in high risk patients.     

Mediastinal lymph node carcinoma of an unknown primary site: clinicopathological examination

Purpose  We examined the clinicopathological features of four mediastinal lymph node carcinomas from an unknown primary site. Methods  Four patients with mediastinal lymph node carcinoma from an unknown primary site were treated at our hospital during the past 6 years. Results  All of the patients were men, with an average age of 74.0 years (range 70–78 years). Histologically, one lesion was poorly differentiated adenocarcinoma, two were poorly differentiated squamous cell carcinoma, and one was undifferentiated carcinoma. Radical resection of the mediastinal tumor and radiotherapy were performed in two patients, both of whom were still alive with no evidence of recurrence at 44 and 82 months, respectively, after the operation. Thoracoscopic biopsy was performed in two patients, and both underwent chemoradiotherapy. These two patients were alive at 24 and 33 months, respectively, after the biopsies. Conclusion  Radical resection of mediastinal lymph node carcinoma with an unknown primary site has the possibility of a good prognosis. In nonradical cases, it is important to perform a biopsy to make an accurate diagnosis and then administer radiotherapy and/or chemotherapy postoperatively.     

Squamous and basal cell cancers directly invading major salivary glands

Epidermoid carcinoma of the skin of the head and neck may uncommonly involve the parotid gland by either direct extension or metastases to the parotid lymph nodes. The parotid gland contains a rich network of superficial and deep nodes, draining a large area of the facial region, with the preauricular, cheek, ear, and eyelid dominating. Few patients with direct parenchymal invasion of the parotid gland by a simultaneously existing squamous or basal cell carcinoma were reported. We could find no report discussing direct tumoral invasion into the submandibular salivary gland. Three patients with squamous cell carcinomas and 2 with basal cell carcinomas of the skin directly involving the underlying salivary glands are presented. The few authors discussing this subject concur that treatment should include resection of the primary tumor along with parotidectomy. Elective neck dissection and irradiation are proposed. The course of disease, treatment, and survival of our patients are discussed.     

Merkel cell carcinoma: improved outcome with adjuvant radiotherapy

BACKGROUND: Merkel cell carcinoma is an aggressive primary cutaneous neuroendocrine carcinoma. Patients remain at high risk of locoregional and distant relapse despite treatment. Most studies support the incorporation of locoregional adjuvant radiotherapy in reducing the risk of relapse. METHODS: Between 1980 and 2002, 86 patients diagnosed with Merkel cell carcinoma were treated with curative intent at Westmead Hospital, Sydney. Multivariate analysis was performed using Cox regression analysis. Disease-free survival and overall survival was calculated using Kaplan-Meier survival curves. RESULTS: Median age at diagnosis was 75 years (range 46-89 years) in 49 men and 37 women. Median duration of follow up was 31 months (range 6-153 months). Fifty-one (59%) patients presented with a primary lesion, 19 (22%) with a primary lesion and clinical nodal disease and 16 (19%) with lymph node metastases from an unknown primary. A total of 47 of 86 (55%) relapsed with regional nodal relapse, the commonest site of first relapse. Local relapse was similar for patients undergoing surgery (5/37; 14%) compared with surgery and adjuvant radiotherapy (3/25; 12%). Nodal relapse occurred in 14 of 36 (37%) treated with surgery compared with 7 of 38 (18%) patients treated with surgery and adjuvant radiotherapy. Patients treated with surgery and adjuvant radiotherapy experienced a better median disease free survival compared to those undergoing surgery alone (10.5 months vs 4 months; P < 0.01). The 5-year overall and disease-free survival rate for the entire study population was 47% and 25%, respectively. Twenty-six patients (30%) died as a result of Merkel cell carcinoma. CONCLUSION: Merkel cell carcinoma is an aggressive skin cancer. The addition of adjuvant radiotherapy markedly improves regional control rates and should be considered best practice.     

Two cases of primary urethral carcinoma in females

Two cases of primary female urethral carcinoma are presented and discussed. The patients were 70 years old and 65 years old, and the pathological diagnoses were squamous cell carcinoma and adenocarcinoma, respectively. The patient with squamous cell carcinoma had metastasized inguinal lymph nodes at the first consultation, despite the administration of bleomycin, and the tumor had widely metastasized to skin of the lower extremities. She died of cachexia and disseminated intravascular coagulopathy (DIC). The other patient with adenocarcinoma was treated by postoperative cobalt radiation therapy in a total dose of 6,000 rads. After 18 months, she had recurrence of tumor in urethra, and developed Virchow's node metastasis, she died of acute renal failure. Both patients died within two years.     

CLINICAL MANAGEMENT AND TREATMENT OUTCOMES OF MERKEL CELL CARCINOMA

Background: Merkel cell carcinoma (MCC), first described in 1972, is an uncommon, highly malignant tumour of skin. Its aetiology is unknown although the tumour occurs most frequently in sun-exposed sites. This skin cancer is characterized by a high incidence of metastases, local and regional recurrence and has a high mortality. Few survival data beyond 3 years are available. Treatment strategies include wide local excision of the primary and lymph node dissection, as indicated together with adjuvant radiotherapy. The tumour has also been shown to be chemosensitive. Definitive treatment is inconclusive due to the relative rarity of this malignancy. Methods: A retrospective study was undertaken between the years 1985 and 1996 of 33 patients with MCC at Concord Repatriation General Hospital (CRGH). Demographic details were noted, together with the site and appearance of the primary lesion and the sites and date of metastases. The response and outcome to various modalities of treatment were documented. Results: There were 27 men and six women with an average age of 80 years (range: 60–86 years). The primary lesion in the present series most often resembled a basal cell carcinoma (BCC), with 53% occurring in the head and neck region. Twenty-seven patients (82%) developed metastastic disease, with an average interval of 13.4 months between diagnosis of the primary lesion and the development of metastases. The incidence of locoregional recurrence in the present series was 42%. Radiation combined with surgery achieved locoregional control in 15 of 19 patients with primary, regional or recurrent locoregional disease. Fourteen patients died of MCC and five others from unrelated causes. The 14 survivors have a mean survival of 54 months with six patients surviving more than 5 years. Conclusions: Local excision together with regional lymph node clearance as indicated, combined with adjuvant radiation treatment was associated with an improved survival. The role of chemotherapy remains unclear.     

Solitary skin metastasis after lung cancer resection

A 75-year-old woman admitted for an abnormal chest X-ray shadow was found in transbronchial lung biopsy to have malignant cells. After right lower lobectomy with mediastinal lymph node dissection, pathological examination showed primary pulmonary squamous cell carcinoma (pT2N1M0, stage IIB). After discharge, we followed her up as an outpatient, with oral administration of uracil and futrafur (300 mg/day). Five months postoperatively, a subcutaneous mass detected on her back and surgically removed was found histologically to be metastatic squamous cell carcinoma of subcutaneous tissue from lung cancer. No other metastases were found. The patient has survived 3 years and 3 months since primary surgery and remained cancer-free 2 years and 11 months since resection for skin metastasis. Given that skin metastasis is detected when most patients are in an advanced stage of disease, our case was a rare one of solitary skin metastasis after resection for lung cancer.     

Primary Merkel Cell Carcinoma of the Submandibular Gland: When CK20 Status Complicates the Diagnosis

Merkel cell carcinoma is a neuroendocrine tumor that occurs predominantly on the sun-exposed skin, with rare cases in the extracutaneous sites. It represents one of the extremely rare malignant neuroendocrine tumors of the salivary glands. We report a case of primary Merkel cell carcinoma of the right submandibular gland. The preoperative diagnosis was doubtful and the definitive histological diagnosis proved to be very difficult considering the extreme rarity of this tumor. The intraoperative evaluation of the macroscopic characteristics of the lesion led to an elective lymph node dissection. The extreme aggressiveness of the disease has resulted in the necessity of a new post-operative staging and in a multimodal treatment. This is the first primary submandibular gland Merkel cell carcinoma described in the literature. Differential diagnosis may be challenging and proper hematoxylin-eosin staining and immunohistochemical studies are mandatory.     

2[F]-fluoro-2-deoxy-D-glucose positron emission tomography is a sensitive tool for the detection of occult primary cancer (carcinoma of unknown primary syndrome) with head and neck lymph node manifestation.

BACKGROUND: The neck lymph nodes are a common site of metastases from carcinoma of unknown primary (CUP syndrome). 2[(18) F]-fluoro-2-deoxy-D-glucose positron emission tomography (18-FDG-PET) has been shown to be a sensitive tool for detecting primary malignant lesions as well as metastatic spread. We have prospectively investigated the sensitivity of 18-FDG-PET in detecting occult primary carcinomas with manifestation in the head and neck lymph nodes. METHODS: From May 1994 to July 1998, in 723 patients a cancer of the head and neck was diagnosed at the University of Cologne ENT outpatient clinic. The routinely performed staging procedures were chest radiography; full blood count; cervical and liver ultrasound; endoscopy of the nasopharynx, oropharynx, hypopharynx, larynx, and esophagus; and laboratory analyses. After the staging workup, in 27 of 723 patients (3.7%) CUP syndrome had to be presumed because the primary cancer could not be detected. In these patients 18-FDG-PET was performed, and images were reconstructed with a transmission-emission fusion technique. RESULTS: In 7 of 27 patients (26%) 18-FDG-PET revealed an unknown primary: in 2 a bronchial carcinoma, in 2 a nasopharyngeal carcinoma, in 1 a squamous cell carcinoma of the parotid gland, in 1 a squamous cell carcinoma of the hypopharynx, and in 1 a carcinoma of the tonsil. In 4 of 7 patients the occult primary tumor was removed surgically. In 8 of 27 patients therapeutic strategy was changed as a result of the 18-FDG-PET findings. CONCLUSION: 18-FDG-PET should be performed in all patients with CUP syndrome after conventional diagnostic workup fails to identify the primary.     

An ultrastructural analysis of breast carcinoma presenting as isolated axillary adenopathy.

Metastatic adenocarcinoma in the axillary lymph nodes of a female patient often originates from a primary tumor in the ipsilateral breast. Mastectomy may be recommended if adenocarcinoma is found in the axillary nodes even when the primary tumor is not clinically detectable. In these circumstances, the recommendation for mastectomy should be based on the firm histologic diagnosis of adenocarcinoma. In the present report, five female patients are discussed who presented with axillary lymphadenopathy without clinically evident breast masses or mammographic evidence of malignancy. Axillary lymph node biopsies, performed in each patient, were inconclusive after conventional light microscopic examination. Electron microscopy established the diagnosis of adenocarcinoma. These findings were complemented by sex steroid analyses of the tumors where possible. Each patient underwent ipsilateral mastectomy, and in each specimen an occult breast carcinoma was found. The necessity of making a precise tissue diagnosis in all cases of metastatic cancer from an unknown primary is stressed, and special techniques to accomplish this must be considered preoperatively. This is particularly important in the female patient with metastatic breast carcinoma in an isolated axillary lymph node, since ipsilateral mastectomy may be curative.     

Extensive cutaneous metastasis of transitional cell carcinoma of the bladder

Cutaneous metastasis of bladder carcinoma is extremely rare. Iatrogenic implantations have been the main cause in the majority of cases of transitional cell carcinoma with cutaneous metastasis. Otherwise, primary cutaneous metastasis is accepted as the late manifestation of systemic spread. The present paper describes a case of relatively early and extensive skin metastasis of transitional cell carcinoma in a 78-year-old man. The patient had a histopathological diagnosis of poorly differentiated (grade III) muscle invasive transitional cell carcinoma with a staging of T2NOMO 6 months prior to presenting. He presented to our outpatient clinic with a 3-month history of skin lesions as multiple, rubbery subcutaneous nodules. Radiological reinvestigation revealed no other metastatic site (including bone and lung), except for a metastatic nodule in the liver. The present paper reports an interesting and rare case of extensive skin metastasis of transitional cell carcinoma as the primary complaint.     

Metastasizing Basal Cell Carcinoma

Three cases of metastasizing basal cell carcinoma are presented. Metastases to regional lymph nodes occurred in 2 cases, and to both the humerus and the brain in the third. In all 3 patients, local recurrence developed in spite of apparently radical surgical removal of the primary tumour, and histological examination revealed distinct aggressive growth. The presence of metastases provides further evidence of the existence of an aggressive variety of the basal cell carcinoma. In these cases it is of particular importance that initial radical treatment is performed, and that the follow-up of the patients includes a check of the regional lymph nodes.