AN OVERVIEW AND OUR APPROACH IN THE TREATMENT OF MALIGNANT CUTANEOUS TUMOURS OF THE HAND

^INTRODUCTION

Cutaneous tumours represent the most frequent primary malignancies of the hand. Typically, they present as painless lesions on areas of high exposure as the dorsum of the hand and upper extremity¹. The patient’s history and the physical examination represent essential factors in the process of formulating a diagnosis. Characteristics such as the change in size, rapid- or slow-growth, pain, localization, transillumination, firmness and motility are significant when performing an immediate diagnosis in most cases. Occasionally, a systemic workup is necessary in order for diagnostic differentiation, including plain radiographs to distinguish the soft-tissue or bony tissue origin, MRI to define the tissue invasion, CT scan to obtain bony details such as cortical disruption, signs which point to a malignant diagnosis^2-3. Surgical removal of the lesions with appropriate margin resections represents the gold standard of treatment, essential for histological analysis and malignancy staging.

^{MATERIALS AND METHODS}

A total of 354 consecutive patients (211 men, 143 women) with malignant cutaneous tumours of the hand were operated and retrospectively analysed at the Department of Plastic and Reconstructive Surgery, University of Palermo, between 2006 and 2017. Mean age was 69.5 (45–94), no significant difference in age at presentation between sexes was observed. 149 (42%) were BCCs, 124 (35%) SCCs, 81 (22%) melanomas. Treatment was surgical for all of them. In 29 cases (l1 with SCC, 18 with melanoma) homolateral axillary lymphadenectomy was performed because of metastasis; also radio- and chemotherapy were necessary based on the histological diagnosis. Patients with BCC and SCC were followed up at the institute two times a year for a mean of 3.4 years. In case of infiltrative SCC lymph nodes ultrasound examination was required. Patients with melanoma underwent multidisciplinary program of follow-ups, which included both dermatologic and oncologic visits. The frequency of the visits and instrumental examinations (ultrasounds, MRI and CT scan) was correlated to the staging and ranged between two and six times a year, for a mean of eight years.

^RESULTS

The dorsum of the hand, first and second web spaces accounted for more than 90% of squamous and basal cell carcinoma, which is likely related to ultraviolet radiation exposure; the major incidence of malignant tumours on the left hands could be related to the increased ultraviolet radiation exposure on the window-side of the body while driving⁴. Palmar or peri/subungual lesions were infrequent, except for malignant melanoma. The most common BCC subtype was superficial (37.7%), followed by nodular (29.5%), infiltrative (19.3%), and morphoeic (13.2%). According to the histological analysis the most common incomplete excision was in infiltrative BBCs (32%), then the nodular and mixed aggressive (15%), superficial ones (12%) and other various histological types (41%). The recurrence rate, after a mean of 3.1 years, was 4%, which essentially included the infiltrative variant. We accomplished radical excision and full-thickness skin graft for most of the SCCs; in 17 cases the tumour infiltrated the bone, thus we performed finger amputation (see Figure 2g). According to the grading, 35% were well differentiated, 28% moderately differentiated, 18% poorly differentiated and 19% undifferentiated. In eleven cases ultrasound lymph nodes examination demonstrated axillary metastases, which required lymphadenectomy. In one case, the patient died of distant organ metastases two years after the surgery. The rate of recurrence at primary lesion site was 11% mean after 3.8 years from the operation.

The majority of malignant melanomas were nodular (40.6 %), acral lentiginous (34.3%), followed by the superficial spreading (25%) subtype. Surgery with radical excision was the treatment of choice for all lesions. In four of these patients the clinic examination, after being confirmed by ultrasounds, revealed the simultaneous presence of axillary lymph nodes metastases. In 14 cases, micrometastasis to sentinel lymph node biopsy was detected. In total, we performed 18 axillary lymphadenectomies, in which four cases underwent adjuvant therapy. In two of these, after a mean of 5.6 years since the operation, distant organ cutaneous metastases occurred (see Figure 3f–g).

^DISCUSSION

Basal cell carcinoma

Basal cell carcinoma (BCC) arises from keratinocytes of the basal epithelium. The clinical aspect is similar to squamous cell tumours, but generally they are more slow-growing and, therefore, sometimes first assessed months after the patient notices the growth. Several distinct variants of BCC exist: superficial, infiltrative, morphoeic and nodular, which is the most common (Figure 1a). This type is characterized early by pink atrophic skin with telangiectasias, which eventually develops into ulcerated lesions with raised pearly borders. BCC rarely metastasizes, but it can be locally aggressive. Although nonsurgical treatments are available, like topical immunomodulators such as imiquimod, 5-fluorouracil, cryotherapy, photodynamic therapy and deep shaving, surgical excision provides healing with lower recurrence rate, thus is the preferable treatment⁵. Excision with a 4 mm margin for lesions less than 2 cm in diameter is considered adequate, permitting the healing on 95% of patients. For tumours wider than 2 cm, and for larger and morphoeic types (Figure 1b), Mohs’ surgery is recommended, which produces cure rates of 99%⁶. In total we treated 149 cases of BCC, performing radical excision with local flap reconstruction for smaller lesions, while using full-thickness skin graft for larger carcinomas.

Squamous cell carcinoma

Squamous cell carcinoma (SCC) is the second most common skin cancer in humans and the first on the hand, accounting for 75–90% of all hand tumours (Figure 2a), followed in frequency by basal cell carcinoma. It is also the most common malignant lesion of the nailbed, often misdiagnosed as a chronic infection or a traumatic injury⁷. Clinical presentation ranges from erythematous plaques to huge polypoid tumours. Other subtypes include verrucous, ulcerative, Marjolin, and subungual carcinomas. About 20% of the squamous cell carcinomas demonstrate a correlation with premalignant conditions such as actinic keratosis or Bowen’s disease. Like other skin tumours, squamous cell carcinoma is more common in areas of intense ultraviolet light or sun exposure such the dorsal surface of the hand. Risk factors include advancing age, outdoor vacation and sunnier geographic areas. An Australian study has suggested a driver’s window-side of the body is more likely to develop cancers due to increased ultraviolet exposure⁴. The presence of a tumour in the web spaces or on the dorsum of the proximal phalanx is more significantly correlated to an increased rate of metastasis, about 0.5-5.9% ⁸ spreading to axillary lymph nodes, due to the thinner skin and the greater density and size of lymphatic trunks. This increases the importance of early diagnosis and treatment. Also, they demonstrate a major propensity for local recurrence due to a more conservative surgical approach in these areas. The primary treatment is surgical excision, including the subcutaneous fat, with 4 mm margins for tumours that are less than 2 cm in diameter, or 6-10 mm margins for those 2 cm in diameter or larger, or with other clinical high-risk prognostic characteristics^8-9 (Figure 2a, b, c). Margins of excised specimens are marked for orientation in cases where the histological analysis requires re-intervention. Split, full-thickness skin grafts (Figure 2d, e, f) and local, perforator, free flaps are the options of reconstruction for post-resection defects for which primary closure is not possible. The different clinical aspect of SCCs can often be mis-diagnosed. In this case shaving or biopsy can be considered for large and pigmented lesions, or atrophic plaques. The recurrence rates after surgical excision range from 7% to 28%; poorly differentiated cells, lesions with a vertical depth greater than 4 mm, perineural invasion, and rapid growth recurrence, all have poor prognostic factors. Generally, regional lymphadenectomy is not recommended in cases of clinical node-negative disease, but only in cases of palpable nodes. In patients with advanced SCC, selective lymphadenectomy using preoperative radiolymphoscintigraphy and intraoperative vital dye injections to identify the sentinel lymph node, represents a safer option, which may help in staging cases and avoiding complications of the complete axillary node dissection. Current evidence does not promote the sentinel lymph node biopsy as routine use for low-risk tumours given the low rate of lymph node metastasis.¹⁰

In frail and elderly patients who cannot undergo the operation, radiotherapy using the brachytherapy technique could be a well-established alternative in terms of local tumour control, cosmesis and hand function⁷. We operated on 124 patients with SCCs, diverse in clinical presentation, ranging from small erythematous plaques to huge polypoid tumours.

Melanoma

Melanoma is the skin cancer with the lowest incidence among the malignant tumours of the hand, but responsible for the majority of all skin cancer related deaths. Its incidence continues to rise, but it is partly due to increased awareness and screening. In the early stage of development, the tumour usually appears as a slow-growing pigmented lesion (melanoma in situ) (Figure 3a). The acral lentiginous melanoma, a rare type of melanoma arising on the oral mucosa, soles, and palms, can involve the nail unit; in particular the nail matrix (subungual melanoma), the nail plate (ungual melanoma) and the skin lateral to the nail plate (periungual melanoma). Subungual melanoma often starts as a pigment band visible along the length of the nail plate (melanonychia), which can escape early detection (Figure 3b). It becomes wider, more irregular in pigmentation, involving the adjacent nail fold, developing an ulcerated bleeding nodule, or causing nail dystrophy (Figure 3c). Correlation with ultraviolet exposure is not evident such for trunk or extremities; actually, trauma is more likely to play a role, accounting for the greater incidence in the thumb. The nodule’s shape is often associated with the advanced stage, with vertical growth, invasion of subcutaneous tissue, and regional and distant metastasis (Figure 3d). The rate of metastasis increases with the Breslow thickness of the tumour. Other peculiar characteristic of the primary melanoma as prognostic factors in the staging system by the American Joint Committee on Cancer (AJCC)¹¹ is ulceration, which increases the risk of regional lymph nodes and distant metastases. Treatment consists of a full-thickness biopsy to confirm the diagnosis. The aim of the oncologic excision is to remove the entire primary lesion, thus, according to the histopathological and biochemical markers, to perform a wide surgical excision with peripheral margins established by the tumour’s thickness. For melanomas in situ a margin of 5 mm is recommended; for lesions of up to 2 mm in thickness, an excision of 1 cm is proposed and 2 cm for tumours with a thickness greater than 2 mm¹¹. All excisions must include the subcutaneous fat up to the muscular fascia to ensure the complete removal both of the tumour and sub-clinical malignant cells in the cutaneous lymphatics. The reconstruction depends on two main factors: location and size of the melanoma. For dorsal or volar aspect of the hand, wide excision with primary closure, or skin graft or local flap for larger defects, are common. For the fingers it is not possible to perform the excisions with large margins, especially for subungual lesions. In this case, to maintain function and cosmesis, minimal invasive approach as amputation at a level one joint proximal to the melanoma is recommended, in particular for invasive lesions (Figure 3e, f, g). Studies have demonstrated no differences in terms of survival and recurrence rate in case of radical amputation of the digit¹². Treatment of invasive melanoma of the thumb seems further complicated. In case of a loss of its length, many reconstructive strategies were reported, including pollicisation, free toe to thumb transfer, reverse forearm flaps. Sentinel lymph node biopsy is a surgical diagnostic procedure indicated to detect micrometastasis at regional, clinically negative, lymph nodes, in patients with melanomas of 0.8 mm in thickness and larger or in melanomas < 0.8 mm in thickness with ulceration. Axillary lymphadenectomy should be performed in melanoma patients with palpable lymph nodes¹¹. Localized in-transit disease should be removed surgically. Although surgery remains the primary treatment for melanoma, recent advances in adjuvant therapy may offer further survival benefits to patients with multiple in-transit metastases and distant metastases are best treated with systemic adjuvant therapy or isolated lymphatic perfusion. Among our 81 patients, the majority of malignant melanomas were stage T3 at initial presentation (25 cases) (2.01 to 4.00 mm thick), and average surgical margins were well below the minimum recommended for each T stage, based on the 2010 British Association of Dermatologists guidelines¹³.

^CONCLUSION

Hand tumours are common entities and most of them are benign¹⁴. Familiarity with the most frequent lesions allows clinicians to accurately diagnose these disorders, but it is important to stay vigilant to avoid missing the rare malignant diseases. Some features can suggest the malignant nature of a lesion, including rapid growth, pain at rest, size greater than 5 cm, constitutional symptoms, and radiographic signs of invasion into local tissues¹⁵. Surgery with radical excision alone is the preferred strategy of treatment for malignant tumours, which can be accompanied by radiotherapy or chemotherapy on an adjuvant or neoadjuvant basis, depending on the particular tumour¹⁵. Conservative surgery in case of subungual melanoma demonstrates no significant differences in prognosis¹². In our experience three patients died from distant metastases (two for melanoma, one for SCCs); thus, our disease-free survival rate is not statistically significant. Actually, according to the literature, patients with malignant tumours of the hand seem to survive more than those with musculoskeletal tumours arising in other parts of the body¹⁵. The reason is not entirely known. Probably the earlier appearance of symptoms because of the restricted anatomic area determines the diagnosis of the tumour in an earlier, more favourable stage that is associated with improved survival.

Disclosure

None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. This work has not been commissioned or published elsewhere, except for congress abstracts and guidelines. All procedures performed in this study involving human participants were in accordance with ethical standards of the institutional and/or national research committee and with the Helsinki declaration and its later amendments or comparable ethical standards.

Corresponding author:

Massimiliano Tripoli, PhD

Plastic and Reconstructive Surgery, Department of Surgical, Oncological and Oral Sciences, University of Palermo

Via del Vespro 129

90127 Palermo

Italy

E-mail: matripoli@yahoo.it