© Springer International Publishing AG 2018
Keith A. Delman and Viraj A. Master (eds.)Malignancies of the Groinhttps://doi.org/10.1007/978-3-319-60858-7_77. Considerations for Nonmelanoma Skin Cancer: Clinical Presentation
(1)
Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
(2)
Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida, USA
Keywords
GroinInguinalLymphadenectomySentinel node biopsyCompletion node dissectionNonmelanoma skin cancerSquamous cell carcinomaMerkel cell carcinomaSartorius muscle flapExtramammary Paget’s diseaseLymphadenopathy of the groin, or inguinal lymphadenopathy, may be a feature of a number of systemic diseases, both benign and malignant. Benign causes of inguinal lymphadenopathy include infection, as well as vascular and autoimmune disease. Malignant groin lymphadenopathy may derive from primary skin tumors (melanoma, squamous cell carcinoma, and Merkel cell carcinoma being the most common) of the lower extremity or lower trunk, perineum, reproductive tracts, and lower gastrointestinal tract and leukemias and lymphomas [1]. This chapter focuses on inguinal lymph node metastasis from nonmelanoma cutaneous malignancies.
When evaluating lymphadenopathy in the groin, a complete history and physical examination are paramount and often sufficient to identify the etiology. Risk factors for cutaneous malignancies often include a history of extensive sun exposure and/or immunosuppression, and patients will commonly report a history of prior skin malignancy or prior skin biopsies. Malignant groin adenopathy typically presents as solitary or multiple painless, palpable masses. If there is a history of prior cutaneous malignancy, it is important to examine and palpate the area between the primary lesion and groin for any evidence of in-transit disease.
A diagnosis can be established by fine needle aspiration (FNA) or core needle biopsy of a palpable lymph node. However, if biopsies are negative or inconclusive, an excisional biopsy is warranted. Once a diagnosis of metastatic disease is established, full-body cross-sectional imaging, if appropriate for the diagnosis at hand, should be obtained to evaluate for further evidence of systemic disease. This can include magnetic resonance imaging (MRI) of the brain; computed tomography (CT) of the chest, abdomen, and pelvis; or full-body positron emission tomography (PET).
Differential Diagnosis
Cutaneous Squamous Cell Carcinoma
Cutaneous squamous cell carcinoma (SCC ) accounts for approximately 20% of all nonmelanoma skin cancer cases [2]. Derived from the superficial layer of the epidermis, it develops most frequently in elderly males and in sun-exposed areas, especially the head, neck, and upper extremities. Ultraviolet (UV) radiation is the most common cause of cutaneous SCC. Immunosuppression, chronic inflammation, and certain chemical agents have also been associated with increased risk for the development of these tumors [3]. Classically, lesions present as a painless, slow-growing nodule(s) that is often ulcerated or with thickened, plaque-like features. Typically, there is a precursor lesion, such as actinic keratosis or SCC in-situ, also known as Bowen’s disease [2, 3].
For the most part, SCC is a treatable disease, with an excellent prognosis and cure rates reported as high as 97% [4]. However, certain subtypes of SCC and clinical scenarios are found to be more aggressive and have a higher risk for regional and distant spread. These higher-risk cases include tumors >2 cm in diameter or 2 mm in thickness, poorly differentiated tumors, tumors with perineural invasion, recurrent SCCs, and those in immunosuppressed patients [5–7]. These higher-risk lesions require more aggressive surgical resection and often the addition of radiation therapy.
Merkel Cell Carcinoma
Merkel cell carcinoma (MCC ) is a rare neuroendocrine tumor of the skin, characterized by rapid growth and a high propensity for local, regional, and distant spread. The total estimated incidence in 2003 was 1300 cases, with one study reporting its incidence to have tripled from 0.15 cases per 100,000 in 1986 to 0.44 cases per 100,000 in 2001 [8–10]. Located in the dermo-epidermal junction, Merkel cells are thought to be neurotactile cells with neuroendocrine features [10]. Histologically, MCC is very similar to small-cell carcinoma of the lung; therefore, immunohistochemical analysis with numerous markers including CK20 and TTF-1 staining is needed to differentiate MCC from other small-cell tumors [9].
Clinically, MCC characteristically appears as a painless, erythematous to violaceous nodule most frequently in the head and neck of elderly individuals. As seen in cutaneous SCC, sun exposure and immunosuppression are established risk factors, with one study reporting a 23.8-fold increase in MCC tumor development after solid organ transplantation [11]. MCC has also been found to be associated with infection by the Merkel cell polyomavirus, possibly acting synergistically with previously mentioned risk factors [12].
MCC typically behaves aggressively, with a higher mortality rate than most cutaneous malignancies. Survival rates for this disease have been reported between 20 and 80% [13]. Local failure is common and can occur in up to one-third of patients. Regional nodal involvement is also frequent, estimated to be as high as 30% at the time of diagnosis [14–16].
Extramammary Paget’s Disease
Extramammary Paget’s disease (EMPD ) is a rare form of intraepithelial adenocarcinoma that originates from apocrine glands of the skin. It is most commonly found in the perineum, perianal region, and vulva. Peak incidence occurs between 50 and 80 years of age [17]. Diagnosis is best made by biopsy and immunohistochemical staining, demonstrating large round cells with centrally situated nuclei and CK7 and CK20 positivity. [18] The natural history of this disease remains widely unknown. There is a subset of EMPD with dermal invasion; though it is not clear whether EMPD with invasion represents a different disease entity, depth of tumor invasion is the most significant prognostic factor, with >1 mm depth or invasion into the reticular dermis associated with a poorer prognosis [19]. EMPD can also be associated with an underlying adnexal or visceral malignancy. In one review, 12% of patients with EMPD had a concurrent underlying internal malignancy [20].
Treatment of the Primary Malignancy
Squamous Cell Carcinoma
Conventional surgical resection or Mohs micrographic surgery (MMS) is the treatment of choice for most cutaneous SCC. Cure rates as high as 97% with negative margins have been reported in the literature [4, 21]. Recommended margin size depends on the histologic characteristics of the lesion. For conventional excision, the recommended margin is 4–6 mm for low-risk lesions and wider margins of 1 cm typically for high-risk tumors [4]. Larger surgical margins may not be feasible in certain anatomic locations and in situations where there is a risk of severe functional and/or cosmetic morbidity. In this setting, MMS is recommended to confirm complete removal of the tumor.
Radiation therapy (RT) has been used as both a primary and adjuvant therapy in the treatment of SCC. In low-risk lesions or tumors of the lip and eyelid, results have been comparable to that of surgery for primary treatment [21]. However, RT usually requires an intensive treatment schedule for multiple weeks and does not allow for histologic confirmation of tumor margins. Therefore, RT as the sole treatment modality is currently only recommended for those patients who are not surgical candidates or in locations where surgical resection would result in poor cosmetic or functional outcomes.
Merkel Cell Carcinoma
For all patients with MCC , wide excision with 1–2 cm margins and routine sentinel lymph node biopsy are recommended. Factors traditionally associated with SLNB positivity and overall survival include increasing tumor diameter and the presence of lymphovascular or angiolymphatic invasion [15, 16]. The authors’ experience of 191 patients with MCC undergoing SLNB showed a >10% chance of a positive SLN even in the thinnest and smallest tumors. Furthermore, increasing tumor diameter and increasing tumor depth were shown to be independent prognostic factors of worse overall survival [22].
Extramammary Paget’s Disease
For EMPD , surgical treatment with wide excision is the treatment of choice. It is currently unclear what size the surgical margin should be to achieve negative margins; however, 1–2 cm margins are routinely obtained [23]. Determining a clear surgical margin at the time of operation can be challenging, as Paget cells are often difficult to recognize on frozen sections. In a series of 48 patients with EMPD, the false-negative rate for frozen sections was 10.4% [24]. However, when combined with intraoperative immunostaining of CK-7, MMS has shown to be of comparable value with wide excision [25].
Recent studies have shown conflicting data regarding the association of SLNB and survival. In a series of 151 patients with EMPD, Fujisawa and colleagues recently reported similar survival outcomes between patients with positive and negative SLNB [26]. In contrast, Ogata and colleagues conducted a similar study of 59 patients with EMPD and reported a 5-year survival rate of 100% among negative SLNB patients versus 24% for those patients with positive SLNB (p < 0.005) [27]. Further studies are needed to develop a consistent treatment algorithm and staging guidelines.
Superficial Inguinal Lymph Node Dissection
In addition to treating the primary lesion, the nodal basin has to be addressed in the case of locoregional spread. Superficial inguinal lymph node dissection (ILND) (inguinofemoral lymphadenectomy) involves removal of the node-bearing tissues in the femoral triangle and the lymphatic tissues superficial to the external oblique aponeurosis above the inguinal ligament. Our method of ILND is outlined as follows [28].
Patients are placed in supine position and the affected extremity is gently frog-legged. Antibiotics are given within 30 min of the skin incision with a first-generation cephalosporin or the equivalent in the penicillin or cephalosporin-allergic patient. Patients with a personal or family history of thrombosis should receive deep venous thrombosis prophylaxis with low molecular weight heparin, and all patients should have bilateral lower extremity sequential compression devices placed. General anesthesia is given, and long-acting paralytics during induction are avoided to allow for stimulation of motor nerves during the procedure.
The technique of inguinofemoral lymphadenectomy varies slightly among surgeons; there are also several steps that tend to be more controversial. Commonly, a lazy “S” incision overlying any palpable adenopathy and which includes a prior biopsy site, seroma cavity, or sentinel lymph node biopsy scar is made. If an ilioinguinal lymphadenectomy is performed, this incision can be extended cranially. In some patients, if a sentinel lymph node biopsy scar is present above the inguinal ligament, then a transverse incision to incorporate the scar and a vertical counter incision below the inguinal ligament to remove the nodes in the femoral triangle is made. Skin flaps are then raised to clear the boundaries of dissection, which include the sartorius muscle laterally, the adductor longus medially, and the apex of the femoral triangle where the sartorius and adductor longus cross distally. Care is taken to avoid excessively thin flaps to prevent skin necrosis. Superiorly, the lymphatic tissues which are superficial to the external oblique fascia and which are bounded by the pubic tubercle, the anterior superior iliac spine, and the inguinal ligament are also removed. The external oblique fascia is preserved, while the fascia of the sartorius and adductor longus are typically incised. Lymphatic vessels should be ligated or clipped to decrease seroma or lymphocele formation.
During the course of dissection, the saphenous vein is encountered near the “apex” of the triangle and ligated distally (and later at the saphenofemoral junction). Saphenous vein preservation may be performed in an effort to decrease the risk of lymphedema. Despite the theoretical benefit, there are no randomized studies that demonstrate decreased lymphedema rates with this practice. In retrospective studies of groin dissection for carcinoma of the vulva, saphenous vein preservation is associated with decreased short- and long-term complications including cellulitis, wound dehiscence, and chronic lymphedema [29, 30]. Sabel et al. compared outcomes for patients undergoing inguinal lymph node dissection for sentinel lymph node-positive disease versus for palpable lymphadenopathy [31]. When the saphenous vein was ligated, the wound complication rate was 20%, and the lymphedema rate was 30% compared to 7% and 13%, respectively, when the saphenous vein was preserved, though this did not reach statistical significance. In a meta-analysis, four trials reported the rates of lymphedema with saphenous vein sparing technique; pooled results demonstrated a lower rate of lymphedema, acute cellulitis, and wound breakdown [32]. Still, some authors propose saphenous vein preservation only in select cases, such as with lymphadenectomy for micrometastatic disease in which the saphenous vein is uninvolved [33].
As dissection continues proximally, skeletonization of the femoral vessels is performed. The femoral artery is identified at the apex, anterior to the femoral vein. As it courses proximally, the femoral artery moves lateral to the femoral vein. All the lymphatic tissues must be dissected off the anterior aspect of the femoral vessels. Care must be taken to prevent injury to the femoral nerve, which is not visualized directly. If the saphenous vein is to be sacrificed, once all of the soft tissues are dissected free and the specimen is only attached by the saphenofemoral junction, the saphenous vein is divided and then suture ligated and tied again, taking care not to narrow the femoral vein.
One step of considerable variability is sartorius muscle transposition to protect the femoral vessels in the event of a wound dehiscence. Some advocate routine sartorius muscle transposition, while others rarely perform this procedure as part of the lymph node dissection. In most cases we perform sartorius muscle transposition, with some exceptions, such as with an incision that is located higher on the groin and not overlying the femoral vessels and in younger and/or very active patients. To start, the tendinous insertion of the sartorius muscle is detached from its origin on the anterior superior iliac spine with electrocautery. The muscle is mobilized medially and laterally to create a tension-free pedicled flap, taking care not to devascularize the muscle belly. A few lateral feeding vessels usually have to be tied off. The muscle is transposed over the femoral vessels and secured to the external abdominal oblique aponeurosis/inguinal ligament with several interrupted horizontal mattress sutures in a staggered fashion to avoid weakening of the fascia.
A retrospective review of patients with vulvar malignancy compared patients with sartorius transposition and those without and found that the transposition group had lower rates of wound breakdown and cellulitis; sartorius transposition was also the only factor associated with decreased wound morbidity [34]. However, in a randomized controlled trial of inguinofemoral lymphadenectomy for vulvar squamous cell carcinoma, there were no differences in wound infection, wound dehiscence, lymphedema, or rehospitalization whether sartorius muscle transposition was performed or not [35].
Prior to wound closure, a closed suction drain is placed in the dissection field and brought out through a separate stab incision adjacent to the wound. The incision is closed with 3-0 Vicryl for the subcutaneous layer and 4-0 Monocryl for a subcuticular layer. The skin is dressed with Dermabond adhesive or similar dressing. The extremity is wrapped in ACE bandages and SCDs are placed on bilateral extremities.
Ilioinguinal (Pelvic) Lymphadenectomy
The same lazy S type of incision may be used if a pelvic lymphadenectomy will be performed in the same setting, though it will need to be lengthened above the inguinal crease for adequate exposure. Lymph nodes removed in a pelvic lymphadenectomy include the obturator and external iliac nodes up to the bifurcation of the internal and external iliac artery; sometimes common iliac nodes can be retrieved, but para-aortic nodes are beyond the field of dissection.
Once the skin incision is extended, external and internal oblique aponeuroses are incised, parallel to the direction of the fibers of each muscle. The peritoneum is retracted superiorly and medially to expose the external iliac artery and vein. The ureter is usually mobilized medially out of the dissection field with this maneuver.
To retrieve the iliac nodal tissues, the external iliac vessel is skeletonized anteriorly from the inguinal ligament to the bifurcation proximally. To remove the obturator nodes, retract the external iliac vein laterally to expose the obturator space. Care must be taken to prevent injury to the obturator nerve, as well as the obturator vein medially, as injury to the vein or its tributaries may be difficult to control. Palpation of the obturator foramen and the pubic rami at the conclusion of the procedure ensure that abnormal nodes are not left behind. We generally do not dissect any tissue deep to the level of the obturator nerve.
After lymph node dissection is complete, a closed suction drain may be placed in the wound bed. The fascia of the internal and external oblique muscles are closed with separate running sutures. The wound is closed in the same fashion as described above for the inguinofemoral portion.
Cloquet’s Node
In the melanoma literature, some authors advocate the use of Cloquet’s node to determine if pelvic lymph node dissection is necessary. Cloquet’s node is the highest node in the inguinal basin at the level of the inguinal ligament; it was first described by the surgeon-anatomist Jules Germain Cloquet [36]. Some surgeons advocate biopsy of Cloquet’s node during groin dissection; if positive, deep pelvic lymphadenectomy would then be performed. However, the utility of Cloquet’s node may be limited in the era of sentinel lymph node biopsy. In their review of patients undergoing groin dissection for sentinel lymph node-positive disease, Chu et al. argue that in the era of SLNB, groin dissections are often performed for an early microscopic disease that is not likely to be Cloquet’s node positive, unlike in prior studies where ILND was performed for palpable adenopathy. In their study, the incidence of a positive Cloquet’s node in patients undergoing groin dissection for SLNB was only 3.8% [37]. In addition, in patients whose Cloquet’s node was positive, pelvic node dissection was already being performed for other indications. In various studies, the positive predictive value of Cloquet’s node ranges from 27 to 79%, though the negative predictive value was higher at 80–97% [38–40].
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