Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• Workup begins with a history and physical examination:
  • For patients with a suspicious lesion
• At the time of diagnosis, patients with BCC:
  • Should be given a full-body skin examination:
    • Because these individuals often have additional, concurrent cancers at other locations
  • A shave, punch, or excisional skin biopsy:
    • May be used for diagnosis of any suspicious lesion:
      • The biopsy should include deep reticular dermis:
        • Because infiltrative histology will often be present only at the deeper, advancing margins of a tumor
    • A punch biopsy:
      • Ranges in size from 2 to 8 mm and involves removing a cylinder of tissue to the level of the subcutaneous fat
    • A shave biopsy:
      • Involves injecting local anesthesia into the epidermis and upper dermis and performing a tangential sample at the base of the wheal
    • Excisional biopsy:
      • Involves removal of the entire lesion with a margin of clinically clear tissue
• Imaging studies:
  • Should be performed when extensive disease:
    • Such as bone involvement, perineural invasion, or deep soft tissue involvement, is suspected

• Location, independent of size, may constitute high risk, and these areas are defined as L, M, and H

• BCCs are the most common cancer in the United States, and the incidence is rapidly rising
• It is estimated that BCCs occur in 2 million Americans annually:
  • Exceeding the incidence of all other cancers
• BCCs are at least two times more common than squamous cell carcinomas (SCCs):
  • The second most common type of skin cancer
• The exact number of cases is difficult to estimate because these cases are not required to be reported to cancer registries
• BCCs generally have a good prognosis due to the low rate of metastasis (0.05%)
• In the U.S., more than 9,500 people are diagnosed with skin cancer every day
  • More than two people die of the disease every hour
• More people are diagnosed with skin cancer each year in the U.S. than all other cancers combined
• At least one in five Americans will develop skin cancer by the age of 70
• Actinic keratosis is the most common precancer:
  • It affects more than 58 million Americans
• Non-melanoma skin cancer:
  • The diagnosis and treatment of nonmelanoma skin cancers in the U.S:
    • Increased by 77% between 1994 and 2014
  • About 90% of nonmelanoma skin cancers are associated with exposure to ultraviolet (UV) radiation from the sun
  • Basal cell carcinoma (BCC):
    • Is the most common form of skin cancer:
      • An estimated 3.6 million cases of BCC are diagnosed in the U.S. each year
  • Squamous cell carcinoma (SCC):
    • Is the second most common form of skin cancer:
      • An estimated 1.8 million cases of SCC are diagnosed in the U.S. each year
  • More than 5,400 people worldwide die of nonmelanoma skin cancer every month
  • Organ transplant patients:
    • Are approximately 100 times more likely than the general public to develop squamous cell carcinoma
  • Regular daily use of an SPF 15 or higher sunscreen reduces the risk of developing squamous cell carcinoma:
    • By about 40^%

• Basal cell carcinomas (BCCs) are believed to arise from the basal layer of epidermis and its appendages;
  • Since they arise from hair follicles:
    • Most lesions are found on sun-exposed areas of hair-bearing skin
• These tumors tend to grow slowly:
  • But when left untreated can lead to invasion of local structures, including:
    • Muscle, cartilage, and bone
• Although BCC is characterized by local and sometimes destructive invasiveness:
  • Metastasis is rare:
    • Occurring in less than 0.05% of cases
• A number of risk factors are associated with the development of BCC:
  • Ultraviolet (UV) solar radiation is considered to be a significant risk factor:
    • Development is thought to arise from intense, intermittent sun exposure:
      • Leading to burns
    • BCC tends to occur in the head and neck area
  • BCC tends to occur in the treatment field of previous radiation therapy (RT):
    • Specially at a young age
  • Settings of immunosuppression, such as:
    • Organ transplantation, HIV infection, or long-term glucocorticoid:
      • Increase the incidence of BCC
• Anatomic location within the high-risk “H zone” or “mask area” of the face and size are:
  • Risk factors for BCC recurrence and metastasis

• Extensive research has led to advances in understanding the genetics of BCC:
  • The sonic hedgehog pathway plays a crucial role in the pathogenesis of BCC:
    • Mutations in this pathway have been implicated in the development of disease
  • Mutations in the PTCH1 (patched 1) gene on chromosome 9q:
    • Which codes for the sonic hedgehog receptor:
      • Are present in 30% to 90% of sporadic BCCs
• Patients with genetic syndromes, including:
  • Xeroderma pigmentosum, albinism, Muir-Torre syndrome, Fanconi anemia, nevoid basal cell carcinoma syndrome or Gorlin syndrome, and Li-Fraumeni syndrome:
    • Have an increased incidence of squamous cell carcinoma (SCC) and BCC

• Although many patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer:
  • Can be successfully treated with endocrine therapy:
    • A proportion are at risk of disease recurrence and death
• Novel, effective treatments are needed to improve outcomes in this patient population:
  • Particularly for those at high risk of recurrence
• Inhibitors of cyclin-dependent kinases (CDK) 4 and 6:
  • Have become standard of care for the adjuvant treatment of high-risk hormone receptor–positive / HER2-negative breast cancer
• More than 90% of patients with breast cancer are diagnosed with early-stage disease:
  • Approximately 70% of whom have hormone receptor–positive / HER2-negative tumors
• Standard therapy for hormone receptor–positive / HER2-negative early breast cancer:
  • Consists of adjuvant endocrine therapy (ie, aromatase inhibitors and / or antiestrogens) with or without ovarian suppression:
    • Meta-analyses have indicated that up to 20% of such patients experience disease recurrence within the first 10 years of endocrine therapy:
      • Including some who present with distant metastases
    • Risk of relapse is especially great for those with high-risk clinical or pathologic features:
      • Clinicopathologic features predictive of relapse for hormone receptor–positive / HER2-negative early breast cancer include:
        • Tumor size, grade
        • Nodal status
        • Increased Ki-67 expression level
        • Residual cancer burden
        • Genomic signature
• CDK4/6 as a Therapeutic Target:
  • CDK4 and CDK6 are involved in regulating cell cycle progression and controlling proliferation
  • CDK4/6 regulation is altered in many solid tumors
  • CDK4/6 is often overexpressed in hormone receptor–positive breast cancers
  • CDK4/6 inhibitors:
    • Target the ATP binding site of CDK4 and CDK6:
      • Blocking their phosphorylation of Rb and inducing cell cycle arrest and apoptosis
    • These compounds differ in their structure and affinity for the ATP binding pocket of CDK4 and CDK6:
      • CDK4/6 inhibitors act in concert with endocrine therapy to inhibit breast cancer growth:
        • Providing the clinical rationale for combination therapy
• Three CDK4/6 inhibitors:
  • Palbociclib, ribociclib, and abemaciclib:
    • Have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of hormone receptor–positive / HER2-negative advanced or metastatic breast cancer (Table)
  • In phase III trials, treatment with these CDK4/6 inhibitors in combination with endocrine therapy:
    • Demonstrated improved progression-free survival compared to endocrine therapy alone:
      • Leading to their approval in this setting
• In light of their benefit in advanced breast cancer, CDK4/6 inhibitors combined with endocrine therapy:
  • Were subsequently evaluated as adjuvant therapy for hormone receptor–positive / HER2-negative early breast cancer

• Adjuvant Clinical Trials of CDK4/6 Inhibitors for Hormone Receptor–Positive/HER2-Negative Early Breast Cancer:
  • Three CDK4/6 inhibitors have been evaluated in combination with endocrine therapy as adjuvant therapy for hormone receptor–positive / HER2-negative early breast cancer:
    • Palbociclib, ribociclib, and abemaciclib
  • To date, only abemaciclib has demonstrated a benefit in invasive disease–free survival compared with endocrine therapy alone and is the only CDK4/6 inhibitor currently approved as adjuvant therapy:
    • For patients with hormone receptor–positive / HER2–negative, node-positive early breast cancer who are at high risk of recurrence and have a Ki-67 level ≥ 20%

• Palbociclib:
  • Palbociclib therapy for hormone receptor–positive / HER2-negative early breast cancer has been studied in two phase III trials:
    • Although neither demonstrated a significant benefit from the addition of palbociclib to endocrine therapy
  • In the PALLAS study:
    • Patients received 2 years of palbociclib plus endocrine therapy or endocrine therapy alone as adjuvant therapy for hormone receptor–positive / HER2-negative high-risk breast cancer (with risk based on anatomic stage)
    • No statistically significant benefit was seen with palbociclib for 4-year invasive disease–free survival or other survival endpoints (Table)
    • The most common adverse events with palbociclib plus endocrine therapy were:
      • Leukopenia, fatigue, thrombocytopenia, anemia, upper respiratory tract infection, and alopecia:
        • With a significantly higher rate of grade 3/4 neutropenia with palbociclib/endocrine therapy compared with endocrine therapy alone:
          • 61.3% vs 0.4%
    • Moreover, 42.2% of patients discontinued palbociclib prior to completion of the planned 2 years of therapy, mainly due to toxicity, based on protocol requirements
• Palbociclib in combination with endocrine therapy:
  • Was also investigated in the PENELOPE-B trial in patients with hormone receptor–positive / HER2-negative breast cancer and residual invasive disease following resection and neoadjuvant chemotherapy who were at high risk of relapse (risk based on clinical pathologic staging–estrogen receptor grading)
    • At a median follow-up of nearly 43 months:
      • No significant increase was observed in estimated 3-year invasive disease–free survival or interim 3-year overall survival (Table 2)
    • The most common adverse events with palbociclib plus endocrine therapy were neutropenia, leukopenia, thrombocytopenia, anemia, hypocalcemia, fatigue, stomatitis, constipation, cough, and infection:
      • The incidence of grade 3/4 neutropenia (70% vs 1%) and leukopenia (56% vs 1%) was significantly increased on the palbociclib arm

• Abemaciclib
  • The monarchE phase III trial compared treatment with abemaciclib plus endocrine therapy to endocrine therapy alone in patients with hormone receptor–positive / HER2-negative early breast cancer who were at high risk of recurrence (based on positive lymph node status, tumor size, histologic grade, and Ki-67 score ≥ 20%):
    • At the 27-month and 42-month follow-up analyses:
      • Patients had a clinically meaningful improvement in invasive disease–free survival with abemaciclib-based therapy compared with the control treatment (Table)
      • The abemaciclib regimen reduced the relative risk of recurrence by about 30%:
        • These were mostly distant recurrences:
          • With longer follow-up, we hope that it will also improve overall survival outcomes
• The incidence of treatment-related adverse events was higher with abemaciclib (98.4% vs 88.8%):
  • The most common of which were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache:
    • Grade 3/4 adverse events were also more frequent with abemaciclib (49.7% vs 16.3%), with a higher discontinuation rate during study treatment (18.5% vs 1.1%)
• Results of the monarchE trial led to FDA approval of abemaciclib in combination with endocrine therapy as adjuvant therapy for high-risk patients with hormone receptor–positive / HER2-negative, node-positive early breast cancer and a Ki-67 score ≥ 20%
• Both the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network® (NCCN) guidelines:
  • Indicate that abemaciclib plus endocrine therapy can be considered for treatment of patients with hormone receptor–positive / HER2-negative, node-positive early breast cancer with high risk of recurrence:
    • Since diarrhea (all grades) occurred in over 80% of patients on the abemaciclib arm in monarchE, patients should be educated on the risk of diarrhea and approaches for mitigation
  • Venous thromboembolism can also occur with abemaciclib therapy (2.3% incidence, all grades, in monarchE²⁴):
    • Caution should be exerted when combining abemaciclib with tamoxifen because both agents can increase risk of thromboembolism:
      • If possible, an aromatase inhibitor with or without ovarian suppression should be used as the preferred endocrine partner with abemaciclib
• Ribociclib
  • While proven effective for hormone receptor–positive / HER2-negative advanced or metastatic breast cancer:
    • Ribociclib has not yet conclusively demonstrated efficacy in hormone receptor–positive / HER2-negative early breast cancer, although several trials are ongoing
  • The phase II LEADER trial (ClinicalTrials.gov identifier NCT03285412) evaluated 1 year of continuous or intermittent ribociclib in this setting:
    • An interim safety analysis revealed that approximately one-third of patients discontinued ribociclib, largely within the first few months of treatment:
      • The most common grade ≥ 3 adverse events resulting in study discontinuation were neutropenia, alanine aminotransferase increase, and aspartate aminotransferase increase
    • Circulating tumor DNA (ctDNA) analysis:
      • Revealed a strong association between detectable ctDNA and disease recurrence
  • ADAPTcycle (NCT04055493) is a phase III trial:
    • Comparing ribociclib plus endocrine therapy to chemotherapy in patients with intermediate-risk hormone receptor–positive / HER2-negative early breast cancer (with risk determined by Oncotype DX score and response to 3 weeks of preoperative endocrine therapy)
  • Another phase III trial, NATALEE (NCT03701334):
    • Is evaluating adjuvant ribociclib and anastrozole in patients with hormone receptor–positive / HER2-negative early breast cancer
• It should be noted that approved dosing differs for these three CDK4 / 6 inhibitors:
  • The shorter half-life of abemaciclib (18.3 hours vs 29.0–32.0 hours for palbociclib and ribociclib):
    • Requires twice-daily dosing to maintain steady-state concentrations:
      • Whereas palbociclib and ribociclib are administered daily for 3 weeks followed by 1-week rest
      • Dosing for palbociclib and ribociclib is based on trials in advanced or metastatic breast cancer since they are not currently approved for early breast cancer
• Ki-67 Expression
  • Expression of the nuclear protein Ki-67 is strongly correlated with breast cancer cell proliferation
  • In patients with hormone receptor–positive / HER2-negative early breast cancer:
    • Ki-67 expression was prognostic for survival:
      • With higher expression levels predicting lower 5-year disease-free survival rates
  • Two large meta-analyses reported Ki-67 cutoffs of 19% and 25% as prognostic for poor survival:
    • Leading to consideration of a cutoff of ≥ 20% as prognostic for survival in patients with hormone receptor–positive breast cancer
  • In monarchE:
    • Patients with high (≥ 20%) Ki-67 expression had a clinically meaningful increased risk of developing invasive disease within 2 years compared with those with low Ki-67, with 2-year invasive disease–free survival rates of 86.1% (95% confidence interval [CI] = 83.1%–88.7%) and 92.0% (95% CI = 89.7%–93.9%), respectively
    • Because approval of abemaciclib as adjuvant therapy for hormone receptor–positive / HER2-negative early breast cancer was based in part on a Ki-67 score ≥ 20%:
      • Tumor Ki-67 expression level should be assessed when considering use of abemaciclib in this setting
      • Ki-67 expression should be measured using an FDA-approved test based on either immunohistochemistry (MIB-1 pharmDx) or molecular profiling (Oncotype DX 21-gene recurrence score)
  • Since benefit for abemaciclib was seen in patients with tumors having either low or high Ki-67:
    • ASCO and NCCN guidelines (in contrast to the FDA indication) suggest that adjuvant abemaciclib may be considered for all patients with hormone receptor–positive / HER2-negative early breast cancer:
      • Based on monarchE intent-to-treat results (which included patients with low and high Ki-67 expression)
    • This is based in part, based on the fact that laboratory assessment of Ki-67 can be quite variable because of differences in immunohistochemistry procedures and interpretation of scoring relative to the 20% cutoff level, which could result in some otherwise eligible patients being denied treatment

“Passaro’s Triangle or Gastrinoma Triangle”

• Edward Peter Passaro (1930-2017) was an American GI surgeon, who described his eponymous triangle in 1984.

👉Gastrinomas secrete supra-physiologic levels of the hormone gastrin, resulting in a clinical syndrome (Zollinger-Ellison syndrome [ZES]), whereby the hypersecretion of gastric acid results in peptic ulcer disease & diarrhea. Common locations for gastrinomas are in the pancreatic head & duodenum, although extra-anatomic tumors may arise in 5% to 15% of cases.

👉The gastrinoma triangle, defined by the junctions of the
(1) cystic duct and common bile duct
(2) neck & body of the pancreas, and
(3) second & third portions of the duodenum, therefore encompasses the majority of gastrinomas

👉Pancreatic gastrinomas comprise 25% of all gastrinomas, & most (50% to 88%) arise in the duodenum, most often in the first portion of the duodenum. There is a predilection for males with ZES; approximately 20% of cases occur in association with MEN-1, and the remaining 80% are sporadic.

𝗥𝗲𝗳: Mastery of surgery 7th ed.

#Arrangoiz #Surgeon #Teacher #CancerSurgeon

• The Multicenter Selective Lymphadenectomy Trial 2 (MSLT-2):
  • Was recently published in June 2017:
    • Which evaluated completion lymphadenectomy versus observation following positive sentinel lymph node biopsies for metastatic melanoma
  • There was no significant difference:
    • In disease-specific survival among the two treatment groups
  • Key limitations to the study were:
    • That it mostly included patients with a low burden of disease (% nodal involvement, largest metastatic focus, and number of positive nodes) in their sentinel lymph nodes
    • The study has limited median follow-up:
      • 43 months
    • Furthermore, it is important to note that there was a significant difference in disease-free survival between groups and that subjects in the study did not receive contemporary systemic therapy
  • Debate remains for which subset of patients would benefit most from completion lymphadenectomy:
    • However, it is reasonable for most of these patients to be observed closely with:
      • Nodal ultrasounds:
        • Every 4 months for the first 2 years
        • Every 6 months for years 3 to 5
        • Then annually.
• References:
  • Faries MB, Thompson JF, Cochran AJ, et al. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med. 2017; 376(23): 2211-2222.

• The NSABP B35 trial:
  • Was a phase 3 clinical trial that randomized postmenopausal women with ER+ DCIS (n = 3,104) to either 5 years of anastrozole or tamoxifen following breast-conserving surgery and radiation
  • The trial sought to determine how effective anastrozole was compared to tamoxifen in preventing a breast cancer occurrence
  • With a median follow-up of 9 years:
    • Investigators found significantly fewer breast cancer events in the anastrozole group (n = 90) than in the tamoxifen group (n = 122)
  • The 10-year breast cancer event rate was lower among women randomized to anastrozole compared to tamoxifen:
    • 6.9% [anastrozole] vs. 10.9% [tamoxifen], HR 0.73, p=0.02:
      • This recorded difference in breast cancer events was attributable almost entirely to younger postmenopausal women less than 60 years of age who received tamoxifen:
        • Women less than 60 receiving tamoxifen had nearly twice the events as those receiving anastrozole:
          • Events on tamoxifen: 63 vs events on anastrozole: 34, HR 0.53 (0.35-0.80), p=0.0026
      • Interestingly, the difference between treatments did not become apparent until after 5 years of follow-up, likely due to the low number of events in both groups
    • There was no difference in overall survival (OS) between the two treatment groups:
      • The 10-year estimates for overall survival were 92.1% for the tamoxifen group and 92.5% for the anastrozole group (p=0.38)
• In B-35, anastrozole was found to further significantly reduce the rate of contralateral invasive cancer compared with tamoxifen
• Based on this trial and others:
  • Aromatase inhibitors are the preferred adjuvant hormonal therapy for ER+ disease in post-menopausal women with either DCIS or invasive breast cancer, provided they have no contraindications to taking an aromatase inhibitor
• References
  • Margolese RG, Cecchini RS, Julian TB, Ganz PA, Constantino JP, Vallow LA, et al. Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. Lancet. 2016;387(10021):849-856
  • M Baum, AU Budzar, J Cuzick, et al., ATAC Trialists’ Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial. Lancet. 2002;359(9324):2131-2139.

• Eccrine carcinoma is an extremely rare neoplasm of the skin:
  • That accounts for approximately 0.005% of malignant epithelial neoplasia
• It arises from the eccrine sweat glands:
  • There are least 10 described subtypes
• Due to the rarity of these neoplasms:
  • Exact etiology and clinical recommendations are not clear
• Most of these tumors are:
  • Slow-growing, solitary, dermal nodules:
    • That often arise from pre-existing benign skin lesions
• Most common distribution is seen in:
  • The head, neck, and extremities
• The diagnosis is often delayed:
  • Because of its relative rarity as well as difficulty in identification with traditional light microscopy
• Recurrence is common
• A wide local excision is the recommended treatment of choice:
  • With a 70% to 80% cure rate
• Mohs microsurgery:
  • Can be used on cosmetically sensitive areas
• Predictive factors for recurrence include:
  • Tumors thicker than 7 mm
  • Lymphovascular invasion
  • Greater than 14 mitoses per high power field
  • Dermal infiltration
• Performing SLN biopsy on these patients is controversial:
  • Lymph node metastasis is relatively rare and sentinel lymph node biopsy:
    • Is not routinely performed for all cases
• Distant metastases are rare and cross-sectional imaging for staging work-up should be performed only when clinically indicated
• Recurrent tumors:
  • Are high risk for locoregional failure:
    • Should be considered for a sentinel lymph node biopsy
• Distant metastasis is rare and any additional staging scans are not recommended
• Radiation and chemotherapy have not demonstrated any significant benefit in the adjuvant setting
• References
  • Barnes M, Hestley A, Murray DR, Carlson GW, Parker D, Delman KA. The risk of lymph node involvement in malignant cutaneous adnexal tumors. Am Surg. 2014;80:270-274.
  • Kampshoff JL, Cogbill TH. Unusual skin tumors: Merkel cell carcinoma, eccrine carcinoma, glomus tumors, and dermatofibrosarcoma protuberans. Surg Clin North Am. 2009;89:727-738.
  • Luz Mde A, Ogata DC, Montenegro MF, Biasi LJ, Ribeiro LC. Eccrine porocarcinoma (malignant eccrine poroma): A series of eight challenging cases. Clinics (Sao Paulo). 2010;65:739-742.
  • Wick MR, Goellner JR, Wolfe JT III, Su WP. Adnexal carcinomas of the skin, II: extraocular sebaceous carcinomas. Cancer. 1985;56:1163-1172.

• Subungual melanomas:
  • Are rare subtypes of melanoma:
    • Accounting for 0.7% to 3.5% of all reported cases
    • The hallux and thumb are the most commonly affected sites
  • Antecedent trauma:
    • Has been reported in 25% to 55% of patients
  • Diagnosis is often delayed because of:
    • Inadequate biopsies
    • Lesion neglect
    • Confusion with benign melanonychia, hematoma, chronic trauma, or fungal nail infection (onychomycosis)
• The classic features suggestive of melanoma include:
  • Melanotic lesions arising from the nail matrix and longitudinal melanonychia:
    • Defined as a band of pigmentation extending from the proximal nail fold / lunula throughout the nail to the free edge
    • Any band greater than 3 mm in width or associated with discoloration of the lateral or proximal nail folds (Hutchinson’s sign):
      • Mandates biopsy of the nail matrix and bed with either incisional or punch techniques:
        • Partial or total avulsion of the nail plate is usually needed to perform biopsy
• Management of these lesions requires sound oncologic resection with consideration of functional deficits:
  • Margin principles in melanoma are maintained:
    • Which means amputation is often necessary
  • Special consideration is given to the hallux and thumb:
    • As the complete loss of either can cause substantial disability
  • For the hallux amputation of the digit preserves the metatarsal head, and for the thumb, efforts are made to preserve bone proximal to the interphalangeal joint, if appropriate margins allow:
    • Excision of the nail bed, matrix, and proximal nail fold will not provide adequate margins
• Mohs micrographic surgery has been used in several small series for selected cases of melanoma-in-situ only, and this technique would not provide adequate resection of this melanoma deeper melanomas
• Amputation of the thumb just proximal to the interphalangeal joint is the best approach:
  • As it provides for adequate margins while preserving a stump for some functional use. Radical amputation would also provide adequate margins, but the functional deficit created is unnecessary
• References:
  • Ross MI. Excision of primary melanoma. In: Balch CM, Houghton AN, Sober AJ, Soong S-J, eds. Cutaneous Melanoma. 5th ed. St. Louis: Quality Medical Publishing; 2009:251-274.
  • Sureda N, Phan A, Poulalhon N, Balme B, Dalle S, Thomas L. Conservative surgical management of subungal (matrix derived) melanoma: report of seven cases and literature review. Br J Dermatol. 2011;165:852-858.
  • Tan KB, Moncrieff M, Thompson JF, et al. Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting. Am J Surg Pathol. 2007;31:1902-1912.