Joi B. Carter

Factors Predictive of Recurrence and Death From Cutaneous Squamous Cell Carcinoma A 10-Year, Single-Institution Cohort Study

IMPORTANCE Although most cases of cutaneous squamous cell carcinoma (CSCC) are easily cured with surgery or ablation, a subset of these tumors recur, metastasize, and cause death. We conducted the largest study of CSCC outcomes since 1968. OBJECTIVE To identify risk factors independently associated with poor outcomes in primary CSCC. DESIGN A 10-year retrospective cohort study. SETTING An academic hospital in Boston. PARTICIPANTS Nine hundred eighty-five patients with 1832 tumors. MAIN OUTCOMES AND MEASURES Subhazard ratios for local recurrence, nodal metastasis, disease-specific death, and all-cause death adjusted for presence of known prognostic risk factors. RESULTS The median follow-up was 50 (range, 2-142) months. Local recurrence occurred in 45 patients (4.6%) during the study period; 36 (3.7%) developed nodal metastases; and 21 (2.1%) died of CSCC. In multivariate competing risk analyses, independent predictors for nodal metastasis and disease-specific death were a tumor diameter of at least 2 cm (subhazard ratios, 7.0 [95% CI, 2.2-21.6] and 15.9 [4.8-52.3], respectively), poor differentiation (6.1 [2.5-14.9] and 6.7 [2.7-16.5], respectively), invasion beyond fat (9.3 [2.8-31.1] and 13.0 [4.3-40.0], respectively), and ear or temple location (3.8 [1.1-13.4] and 5.9 [1.3-26.7], respectively). Perineural invasion was also associated with disease-specific death (subhazard ratio, 3.6 [95% CI, 1.1-12.0]), as was anogenital location, but few cases were anogenital. Overall death was associated with poor differentiation (subhazard ratio, 1.3 [95% CI, 1.1-1.6]) and invasion beyond fat (1.7 [1.1-2.8]). CONCLUSIONS AND RELEVANCE Cutaneous squamous cell carcinoma carries a low but significant risk of metastasis and death. In this study, patients with CSCC had a 3.7% risk of metastasis and 2.1% risk of disease-specific death. Tumor diameter of at least 2 cm, invasion beyond fat, poor differentiation, perineural invasion, and ear, temple, or anogenital location were risk factors associated with poor outcomes. Accurate risk estimation of outcomes from population-based data and clinical trials proving the utility of disease-staging modalities and adjuvant therapy is needed.

Outcomes of Primary Cutaneous Squamous Cell Carcinoma With Perineural Invasion: An 11-Year Cohort Study

OBJECTIVE To identify factors associated with poor outcomes in perineurally invasive squamous cell carcinoma. DESIGN Retrospective cohort study. SETTING Two academic hospitals in Boston, Massachusetts. PATIENTS Adults with perineural SCC diagnosed from 1998 to 2008. MAIN OUTCOME MEASURES Hazard ratios (HRs) for local recurrence, nodal metastasis, death from disease, and overall death, adjusted for known prognostic factors. RESULTS A total of 114 cases were included, all but 2 involving unnamed nerves. Only a single local recurrence occurred in cases with no risk factors other than nerve invasion. Tumors with large nerve (≥ 0.1 mm in caliber) invasion were significantly more likely to have other risk factors, including diameters of 2 cm or greater (P<.001), invasion beyond the subcutaneous fat (P<.003), multiple nerve involvement (P<.001), infiltrative growth (P=.01), or lymphovascular invasion (P=.01). On univariate analysis, large nerve invasion was associated with increased risk of nodal metastasis (HR, 5.6 [95% CI, 1.1-27.9]) and death from disease (HR, 4.5 [95% CI, 1.2-17.0]). On multivariate analysis, tumor diameter of 2 cm or greater predicted local recurrence (HR, 4.8 [95% CI, 1.8-12.7]), >1 risk factor predicted nodal metastasis (2 factors: HR, 4.1 [95% CI, 1.0-16.6]), lymphovascular invasion predicted death from disease (HR, 15.3 [95% CI, 3.7-62.8]), and overall death (HR, 1.1 [95% CI, 1.0-1.1]). Invasion beyond subcutaneous fat also predicted overall death (HR, 2.1 [95% CI, 1.0-4.3]). CONCLUSIONS Squamous cell carcinoma involving unnamed small nerves (<0.1 mm in caliber) may have a low risk of poor outcomes in the absence of other risk factors. Large-caliber nerve invasion is associated with an elevated risk of nodal metastasis and death, but this is due in part to multiple other risk factors associated with large-caliber nerve invasion. A larger study is needed to estimate the specific prognostic impact of nerve caliber.

PD‐1, S‐100 and CD1a expression in pseudolymphomatous folliculitis, primary cutaneous marginal zone B‐cell lymphoma (MALT lymphoma) and cutaneous lymphoid hyperplasia

Pseudolymphomatous folliculitis is a lymphoid proliferation that clinically and histopathologically mimics primary cutaneous extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma). In this study, we assessed the diagnostic value of three immunohistochemical markers, programmed death‐1 (PD‐1), CD1a and S100.

Adult T-Cell Leukemia/Lymphoma

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell lymphoma caused by long-term infection with human T-lymphotropic virus 1 (HTLV-1). Patients with ATLL have an extremely poor prognosis, their disease complicated by multidrug resistance of malignant cells, infection due to impaired T-cell mediated immunity, hypercalcemia, and multiple organ failure. Half of patients develop cutaneous manifestations. The cutaneous lesions of ATLL are highly varied and include erythroderma, purpuric papules, and plaques. This chapter addresses the clinical presentation, prognosis, treatment, histopathology, immunohistochemistry, and molecular characteristics of this disease. It closes with a differential diagnosis and clinical case.

The Z-advancement flap for reconstruction of lateral nasal tip and medial alar defects.

BACKGROUND Reconstruction of lateral nasal tip and medial alar defects is challenging. Contour, symmetry, and skin texture of the nose, along with adequate nasal airway patency, should be preserved. The Z‐advancement flap is a novel reconstruction technique designed for optimal cosmesis and function. OBJECTIVE To evaluate the aesthetic and functional outcomes of Z‐advancement flap nasal reconstruction. MATERIALS AND METHODS Twenty‐nine consecutive patients with defects 1 cm or less in diameter on the lateral nasal tip or medial ala underwent Z‐advancement flap repair. Patients completed a survey assessing cosmesis and airway patency. Three physicians evaluated standardized photographs on visibility of scar lines, erythema and telangiectasia, and contour and symmetry of the ala and nostril opening. RESULTS Twenty‐eight (96%) patients completed survey questionnaires. All patients were satisfied with the look and feel of their reconstructed nose. Twenty‐four (86%) saw no visible scar or abnormality. Postoperative photographs were available for review in 19 (66%) patients. In 95% to 96% of physician ratings, scars were invisible or visible only on close inspection, and alar symmetry was unchanged or only slightly altered. In 88%, nostril opening symmetry was unchanged or slightly altered. CONCLUSIONS The Z‐advancement flap preserves aesthetic subunits of the nose to produce excellent cosmesis and patient satisfaction for defects of the lateral nasal tip or medial ala 1 cm or less in diameter.

Case records of the Massachusetts General Hospital. Case 24-2013. A 53-year-old woman with erythroderma, pruritus, and lymphadenopathy.

Dr. Allison Larson (Dermatology): A 53-year-old woman was admitted to this hospital because of persistent erythroderma and lymphadenopathy. The patient had been well until approximately 18 months earlier, when a diffuse, pruritic rash developed. During the next year, the rash progressed to total-body erythema. A diagnosis of psoriasis was made; topical glucocorticoids and oral cephaloridine were administered, without improvement. Five months before admission, the rash worsened. On examination at another facility, there was reportedly an extensive erythroderma of the extremities that was thought to be psoriasis; prednisone was administered orally. Shortly thereafter, fever and leg swelling developed, and the patient was admitted to another hospital. On examination, the temperature was 38.1°C, and the pulse 145 beats per minute. Over the extremities was a diffuse, scaly, erythematous rash with a small amount of serous drainage, and there was warm, nonpitting edema of the legs; the remainder of the examination was normal. Blood levels of electrolytes, calcium, magnesium, phosphorus, and B-natriuretic peptide were normal, as were the results of tests of coagulation and liver and renal function; tests for rheumatoid factor, syphilis, and hepatitis B and C viruses were negative. Other test results are shown in Table 1. A chest radiograph was normal. Pathological examination of a skinbiopsy specimen of the left leg showed psoriasiform epidermal hyperplasia with parakeratosis, as well as a mixed inflammatory infiltrate in the superficial dermis, features suggestive of a hypersensitivity reaction. A diagnosis of psoriasis complicated by cellulitis was made, and broad-spectrum antibiotics and prednisone were administered. Cultures of the skin grew methicillin-sensitive Staphylococcus aureus, and cultures of the blood were sterile. Fevers resolved, and the patient was discharged on the seventh day, taking dicloxacillin (10-day course, orally) and topical glucocorticoids. During the next 4 months, the erythroderma persisted, with intermittent exacerbations attributed to cellulitis. Three months before admission to this hospital, while the patient was taking trimethoprim–sulfamethoxazole, urticaria developed, associated with peripheral-blood eosinophilia. Levels of cobalamin (vitamin B12)

Introduction to the B-Cell Lymphomas

The human body contains a vast array of B cells, with phenotypes ranging from the naive B cell to the centrocyte, centroblast, immunoblast, plasmablast, and plasma cell. Each of these B-cell subsets has different functional, proliferative, and migratory capacities, and the diversity of cutaneous B-cell lymphoma (CBCL) reflects the variety of non-neoplastic B-cell counterparts. The WHO-EORTC classification [1] recognizes four cutaneous B-cell lymphomas: primary cutaneous marginal zone lymphoma (pcMZL or MALT lymphoma), primary cutaneous follicle-center lymphoma (pcFCL), primary cutaneous diffuse large B-cell lymphoma, leg-type (pcDLBCL), and intravascular large B-cell lymphoma (ivLBCL). Here we offer a schema for understanding and distinguishing these lymphomas. Each lymphoma is addressed individually in subsequent chapters.

Contribution of longitudinal follow up and clinical pathological correlation in the diagnosis CD30-positive skin infiltrates†

The diagnosis of a CD30+ cutaneous infiltrate is often difficult and requires clinicopathologic correlation. To further evaluate this challenge, initial clinical and histopathologic diagnoses were correlated with final clinicopathologic diagnosis in 44 cases with CD30 immunopositivity. Dermatopathologic evaluation confirmed the initial clinical diagnosis in 65% of the suspected benign cases, all cases of suspected lymphomatoid papulosis (LyP), and 72% of clinically malignant cases. In the 25 patients with clinical suspicion for lymphoma, the histopathologic diagnoses included lymphoma in 18, LyP in 2, CD30+ lymphoproliferative disorder (CD30 LPD) in 3 and hypersensitivity reaction in 2 patients. Clinicopathologic correlation led to a change in three cases diagnosed histopathologically as anaplastic large cell lymphoma (ALCL) reclassified as LyP type C, and one patient diagnosed as CD30 LPD clinically evolved as herpes virus infection. Furthermore, five cases reported as CD30 LPD received more specific diagnoses after clinicopathologic correlation (LyP type C in three, and ALCL in two patients). Clinicopathologic correlation is essential in establishing the correct diagnosis of CD30 LPD, in particular the distinction of ALCL from LyP type C. In this setting, the histopathologic diagnosis of CD30 LPD is advisable in the absence of clinical data.

Rare presentation of secondary cutaneous involvement by splenic marginal zone lymphoma: report of a case and review of the literature.

Cutaneous lymphomas encompass a broad spectrum of malignancies, including both primary and secondary cutaneous lymphomas. Determining the exact subtype of cutaneous lymphoma offers prognostic importance and directs therapeutic decisions. We describe the case of a 67-year-old woman with cutaneous involvement of splenic marginal zone lymphoma successfully treated with rituximab and bendamustine. We discuss the diagnostic work-up, including the histopathologic findings and treatment of this disease.

Case 24-2013

Dr. Allison Larson (Dermatology): A 53-year-old woman was admitted to this hospital because of persistent erythroderma and lymphadenopathy. The patient had been well until approximately 18 months earlier, when a diffuse, pruritic rash developed. During the next year, the rash progressed to total-body erythema. A diagnosis of psoriasis was made; topical glucocorticoids and oral cephaloridine were administered, without improvement. Five months before admission, the rash worsened. On examination at another facility, there was reportedly an extensive erythroderma of the extremities that was thought to be psoriasis; prednisone was administered orally. Shortly thereafter, fever and leg swelling developed, and the patient was admitted to another hospital. On examination, the temperature was 38.1°C, and the pulse 145 beats per minute. Over the extremities was a diffuse, scaly, erythematous rash with a small amount of serous drainage, and there was warm, nonpitting edema of the legs; the remainder of the examination was normal. Blood levels of electrolytes, calcium, magnesium, phosphorus, and B-natriuretic peptide were normal, as were the results of tests of coagulation and liver and renal function; tests for rheumatoid factor, syphilis, and hepatitis B and C viruses were negative. Other test results are shown in Table 1. A chest radiograph was normal. Pathological examination of a skinbiopsy specimen of the left leg showed psoriasiform epidermal hyperplasia with parakeratosis, as well as a mixed inflammatory infiltrate in the superficial dermis, features suggestive of a hypersensitivity reaction. A diagnosis of psoriasis complicated by cellulitis was made, and broad-spectrum antibiotics and prednisone were administered. Cultures of the skin grew methicillin-sensitive Staphylococcus aureus, and cultures of the blood were sterile. Fevers resolved, and the patient was discharged on the seventh day, taking dicloxacillin (10-day course, orally) and topical glucocorticoids. During the next 4 months, the erythroderma persisted, with intermittent exacerbations attributed to cellulitis. Three months before admission to this hospital, while the patient was taking trimethoprim–sulfamethoxazole, urticaria developed, associated with peripheral-blood eosinophilia. Levels of cobalamin (vitamin B12)