Acute febrile neutrophilic dermatosis (Sweet syndrome) in acute myeloid leukemia patients: a 28-year institutional experience.

INTRODUCTION: Sweet syndrome (SS) is well-known to be associated with underlying hematologic malignancies. The incidence and qualities of SS among novel targeted therapies for acute myeloid leukemia (AML) have not yet been described. METHODS: Through retrospective review of 19432 patients diagnosed with acute/chronic leukemia or myelodysplastic syndromes/ myeloproliferative neoplasms (MDS+/-MPN) over 28 years, we calculated the incidence of SS in the setting of select hematologic malignancies and described the clinicopathologic characteristics of SS in patients with onset of SS after initiation of novel AML-targeted therapies. RESULTS: Overall incidence of SS was 0.36% (95% CI: 0.27% - 0.45%), which was significantly higher among patients with AML (50/5248, 0.94%; 95% CI: 0.71% - 1.25%). Nine AML patients were on 4 classes of novel targeted treatments - IDH1/2 inhibitor alone, FLT3 inhibitor, IDH2 and DOT1L inhibitor, and anti-CD33 therapy. In therapies inducing myeloid blast differentiation, SS occurred at later onset following treatment. CONCLUSIONS: In AML patients with fever and unusual skin lesions, physicians may consider SS earlier which may shorten time to diagnosis. Future assessments of SS among patients treated with novel therapies for AML and molecular studies of biopsies may help further explain this dermatologic adverse event with earlier diagnosis and management of neutrophilic dermatoses in these patients.

Outcomes and prognostic factors in African American and black patients with mycosis fungoides/Sézary syndrome: Retrospective analysis of 157 patients from a referral cancer center.

BACKGROUND: The prevalence of mycosis fungoides/Sézary syndrome (MF/SS) is higher in the black population than in the white population in the United States and worse outcomes have been observed in black patients. OBJECTIVE: To describe the outcomes and to identify prognostic factors in African American and black patients with MF/SS. METHODS: Clinical features and follow-up data were analyzed in 157 self-identified African American or black patients seen during 1994-2018. RESULTS: We included 122 patients with early stage MF and 35 patients with advanced-stage disease (median follow-up of 25 months). Overall, >80% of the patients who died from disease or progressed had erythema or hyperpigmentation without hypopigmentation. Patients with hypopigmentation, either as the sole manifestation or in combination with other lesions, had better overall survival (P = .002) and progression-free survival (P = .014). Clinical stage, TNMB classification, plaque disease, and elevated serum lactate dehydrogenase were also significantly associated with outcomes. Demographic and socioeconomic parameters were not associated with prognosis. LIMITATIONS: A retrospective study at a single cancer center. CONCLUSION: MF/SS manifestations and outcomes in African American and black patients are heterogeneous. Demographic and socioeconomic factors do not seem to have a prognostic role, while clinical characteristics might help in the stratification of risk of progression and shorter survival, allowing for individually tailored therapeutic interventions.

Scleromyxedematous Changes in a Patient With Long-Standing Mycosis Fungoides Who Progressed to Sézary Syndrome.

Mycosis fungoides (MF) variants with different clinicopathologic and immunohistochemical features have been well-delineated. We report a case of scleromyxedematous changes arising in a patient with long-standing MF who progressed to Sézary syndrome (SS) shortly afterward. Total-skin electron-beam radiation therapy resulted in an excellent response, controlling both the MF/SS and the scleromyxedematous lesions; however, the patient died few months later. Although mucin deposition has been described in association with MF/SS (mainly follicular mucinosis in folliculotropic MF), there are limited reports in the literature on dermal mucinosis and scleromyxedematous changes in MF/SS. The mechanism of this association and its prognostic implications requires further investigation.

Unrelated immunodeficiency states may impact outcomes and immune checkpoint molecule expression in patients with mycosis fungoides: A clinicopathologic case-control study.

BACKGROUND: Immunodeficiency (ID) correlates with worse outcomes and decreased immune checkpoint molecule expression in melanoma. The impact of ID in mycosis fungoides (MF) is unknown. OBJECTIVE: Our goal was to evaluate the impact of ID in MF. METHODS: We conducted a case-control study of 17 patients with MF and ID versus age-, stage-, and race-matched controls as a subset of a comparative analysis of 23 patients with MF with ID (prior lymphoma, recent/current pregnancy, HIV, hypogammaglobulinemia, and prior chemotherapy) versus without ID. Programmed cell death 1 (PD1), programmed death ligand 1 (PDL1), forkhead box p3, and interleukin 17 immunohistochemistry was performed on 12 patients with ID and 10 controls. RESULTS: Patients with ID had more treatment failure (14 of 23 vs 5 of 17 [P = .028]), more treatment failure within 3 years of diagnosis (12 of 23 vs 4 of 17 [P = .050]), more angiocentrism (6 of 12 vs 0 of 10 [P = .005]), larger cells (1.92 ± 0.51 out of 3 vs 1.30 ± 0.48 out of 3 [P = .009]), more cases with at least 10% PD1 positivity (9 of 11 vs 4 of 10 [P = .031]) and at least 10% PDL1 positivity (7 of 12 vs 2 of 10 [P = .042]), and a higher average percentage of PD1+ cells (43.27 ± 40.22 vs 11.2 ± 13.62 [P = .028]). No differences in survival, forkhead box p3 expression, interleukin 17 expression, histologic depth, ulceration, granulomatous changes, or syringotropism were seen. LIMITATIONS: This was a small single-center study with heterogeneous immunodeficiencies. CONCLUSION: ID correlated with worse outcomes and increased PD1 and PDL1 expression in MF. Patients with MF and ID may be candidates for immune checkpoint inhibitor therapy, pending further investigation.

Reduced H3K27me3 expression in Merkel cell polyoma virus-positive tumors.

Merkel cell carcinoma is a primary cutaneous neuroendocrine carcinoma, which once metastatic is difficult to treat. Recent mutation analyses of Merkel cell carcinoma revealed a low number of mutations in Merkel cell polyomavirus-associated tumors, and a high number of mutations in virus-negative combined squamous cell and neuroendocrine carcinomas of chronically sun-damaged skin. We speculated that the paucity of mutations in virus-positive Merkel cell carcinoma may reflect a pathomechanism that depends on derangements of chromatin without alterations in the DNA sequence (epigenetic dysregulation). One central epigenetic regulator is the Polycomb repressive complex 2 (PRC2), which silences genomic regions by trimethylating (me3) lysine (K) 27 of histone H3, and thereby establishes the histone mark H3K27me3. Recent experimental research data demonstrated that PRC2 loss in mice skin results in the formation of Merkel cells. Prompted by these findings, we explored a possible contribution of PRC2 loss in human Merkel cell carcinoma. We examined the immunohistochemical expression of H3K27me3 in 35 Merkel cell carcinomas with pure histological features (22 primary and 13 metastatic lesions) and in 5 combined squamous and neuroendocrine carcinomas of the skin. We found a strong reduction of H3K27me3 staining in tumors with pure histologic features and virus-positive Merkel cell carcinomas. Combined neuroendocrine carcinomas had no or only minimal loss of H3K27me3 labeling. Our findings suggest that a PRC2-mediated epigenetic deregulation may play a role in the pathogenesis of virus-positive Merkel cell carcinomas and in tumors with pure histologic features.

Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas.

Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αß T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αß/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases.

Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients.

Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, P<0.0001), age (<70 versus ≥70, P=0.01), sentinel lymph node metastasis pattern (patterns 2-5 versus 1, P=0.02), and immune status (immunocompetent versus suppressed, P=0.03) were independent predictors of outcome, and could be used to stratify Stage III patients into three groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.

Clinico-morphological features of BRAF inhibition-induced proliferative skin lesions in cancer patients.

BACKGROUND: The use of BRAF inhibitors may lead to the development of cutaneous toxicities such as rashes, photosensitivity, alopecia, palmoplantar erythrodysesthesia, and proliferative skin lesions, including keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cuSCCs). The latter are noteworthy for their potential to exhibit malignant features, and they may necessitate invasive treatment. Their prompt identification is of primary importance for directing supportive care efforts and maintaining dose intensity while minimizing the morbidity associated with supportive care interventions. Because such lesions are less familiar to oncologists, this study was designed to characterize their clinico-morphological features, which have not been hitherto described. METHODS: The clinical and dermoscopic characteristics and risk factors of new-onset proliferative skin lesions (benign verrucous lesions and KAs/cuSCCs) developing after the initiation of treatment with vemurafenib, dabrafenib, and XL281 were analyzed; the histopathological diagnoses were ascertained. RESULTS: The majority of the lesions were benign verrucous lesions (78%, n = 87), whereas KAs/cuSCCs represented 22% (n = 25). The median times to biopsy for the initial verrucous lesions and KAs/cuSCCs were 4.8 and 10.5 weeks, respectively. The clinico-morphological features significant for KAs/cuSCCs included a larger size (P < .001), a nodular appearance (P < .001), a central keratin plug (P < .001), a central ulceration or crust (P = .04), an adherent scale (P = .02), an erythematous halo (P = .03), and a scaly ring (collarette; P < .001) at the periphery. CONCLUSIONS: Our findings represent the first detailed description of the clinico-morphological characteristics that permit distinction between the benign and malignant skin lesions induced by BRAF inhibitors. They are valuable for the recognition of lesions that require intervention and/or a dermatology referral versus those that permit provisional monitoring.

Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma.

Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven 'pure' Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52-89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression.

Cutaneous manifestations of human T-cell lymphotrophic virus type-1-associated adult T-cell leukemia/lymphoma: a single-center, retrospective study.

BACKGROUND: Limited data exist regarding cutaneous involvement of adult T-cell leukemia/lymphoma (ATLL), particularly in the United States. OBJECTIVE: We sought to characterize clinical and histopathologic features of ATLL in patients with skin involvement. METHODS: We retrospectively identified patients with ATLL from a single institution given a diagnosis during a 15-year period (1998-2013). Patients were categorized by the Shimoyama classification and stratified into skin-first, skin-second, and skin-uninvolved courses. RESULTS: The study population included 17 skin-first, 8 skin-second, and 29 skin-uninvolved cases. Skin-first patients (6 acute, 1 lymphoma, 4 chronic, 6 smoldering) were overwhelmingly of Caribbean origin (94%). They had longer median symptom duration (11.9 vs 1.9 months, P < .001) and overall survival (26.7 vs 10.0 months, P < .001) compared with skin-second/skin-uninvolved patients. Cutaneous lesion morphology at diagnosis included nodulotumoral (35%), multipapular (24%), plaques (24%), patches (12%), and erythroderma (6%). After initial skin biopsy, 14 of 17 received a non-ATLL diagnosis, most commonly mycosis fungoides (47%). Notable histopathologic findings from 43 biopsy specimens included greater than or equal to 20:1 CD4:CD8 ratio (79%), angiocentrism (78%), CD25(+) (71%), large cell morphology (70%), CD30(+) (68%), epidermal infiltration of atypical lymphocytes (67%) forming large Pautrier-like microabscesses (55%), and folliculotropism (65%). LIMITATIONS: This was a retrospective, single-center, tertiary referral center study with small sample size. CONCLUSION: Skin-first patients with ATLL in the United States are diagnostically challenging. Familiarity with clinicopathologic features may aid in diagnosis.

Clinical and dermoscopic features of combined cutaneous squamous cell carcinoma (SCC)/neuroendocrine [Merkel cell] carcinoma (MCC).

BACKGROUND: Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma, associated with Merkel cell polyomavirus. MCC admixed with squamous cell carcinoma (SCC) is unassociated with polyomavirus, and is genetically distinct. OBJECTIVE: We sought to distinguish clinically and dermoscopically between MCC and SCC/MCC. METHODS: We compared patient data for SCC/MCC (n = 26) and MCC (n = 20), and reviewed clinical and dermoscopic images (n = 9) of SCC/MCC. RESULTS: Patients with SCC/MCC were older (median 76.5 vs 69 years) and more often male (77% vs 60%), and had more nonmelanoma skin cancer (85% vs 25%), malignant extracutaneous tumors (25% vs 5%), lymphoproliferative disorders (23% vs 10%), and immunodeficient/proinflammatory states (77% vs 35%). In all, 58% of SCC/MCC versus 10% of MCC were clinically diagnosed nonmelanoma skin cancer. Patients with SCC/MCC had more metastases (77% vs 40%), more treatment failures (53% vs 45%), shorter survival (41 vs 54 months), and more death from disease (50% vs 40%). SCC/MCC demonstrated marked scale (7/9), and telangiectasia (1/9). Dermoscopically, small dotted and short linear irregular peripheral vessels and central milky-red areas with large-diameter arborizing vessels were seen. LIMITATIONS: The rarity of SCC/MCC limits available data. CONCLUSIONS: SCC/MCC is aggressive, arising within elderly patients' chronically ultraviolet-exposed skin, often in the setting of immunosuppression or inflammation. Dermoscopically, polymorphous vessels in lesions suspicious for nonmelanoma skin cancer are suggestive.

Histopathologic Features of Cutaneous Acute Graft-Versus-Host Disease in T-Cell-Depleted Peripheral Blood Stem Cell Transplant Recipients.

T-cell-depleted (TCD) allogeneic hematopoietic stem cell transplantation demonstrates similar efficacy and reduced incidence and severity of graft-versus-host disease (GVHD) in appropriately selected patients versus T-cell-replete transplantation. The histopathology of cutaneous acute GVHD (aGVHD) after TCD peripheral blood stem cell transplants (PBSCTs) is not described. We identified 13 cases of patients after TCD PBSCT, with definitive aGVHD, and 20 cases of non-aGVHD skin rash in patients after TCD PBSCT, during multidisciplinary review by a dermatopathologist, dermatologist, and transplant physician, incorporating clinical presentation, therapeutic response, and histopathology data. Histopathologic features of aGVHD and non-aGVHD skin rash in TCD PBSCT patients were compared to each other, and also to features recently reported for non-TCD transplant recipients. aGVHD and non-aGVHD skin rash in TCD PBSCT patients' biopsies had similar rates of epidermal acanthosis, dermal melanophages, neutrophils, plasma cells, eosinophils, and extravasated erythrocytes. While satellitosis, exocytosis and adnexal involvement slightly favored aGVHD, more notable differential findings favoring aGVHD were diffuse (vs. focal/absent) basal vacuolization (77% aGVHD vs. 25% non-aGVHD rash), involvement of the entire epidermis (vs. partial thickness) by necrotic keratinocytes (42% aGVHD vs. 0% non-aGVHD rash), and nondense (rather than exuberant) inflammatory infiltrates (77% vs. 20%). After filtering features seen in all TCD samples (epidermal acanthosis, dermal melanophages, neutrophils, plasma cells, eosinophils, and extravasated erythrocytes), the most distinct features belonging to aGVHD-positive TCD samples were diffuse basal vacuolization, slight rather than dense inflammatory infiltrates, and necrotic keratinocytes involving the entire epidermis. Awareness of these features may help when evaluating a skin rash occurring after a TCD transplant.

Jejunal adenocarcinoma with cutaneous metastasis.

Small bowel adenocarcinoma (SBA) is a rare primary gastrointestinal malignancy. We present a 60-year old man who developed a cutaneous metastasis of jejunal adenocarcinoma to his neck. This case highlights the clinicopathologic and immunophenotypic features of this uncommon cutaneous metastasis.

Combined melanocytic and sweat gland neoplasm: cell subsets harbor an identical HRAS mutation in phacomatosis pigmentokeratotica.

Phacomatosis pigmentokeratotica (PPK) is characterized by the co-existence of epidermal nevi and large segmental speckled lentiginous nevi of the papulosa type. PPK, previously explained as 'twin spot' mosaicism due to the postzygotic crossing-over of two homozygous recessive mutations, has recently been shown to derive from one postzygotic activating RAS mutation. Epidermal nevi, including those in PPK, are known to give rise to neoplasms such as trichoblastoma and basal cell carcinoma. Within speckled lentiginous nevi, Spitz nevi and melanoma have been well documented. We report a case of PPK with a combined melanocytic and adnexal neoplasm presenting where the nevi conjoined. Using next-generation sequencing techniques, we were able to identify the same HRAS G13R mutation within both components of the tumor, and to show the absence of additional mutated modifier genes in a panel of 300 cancer-related genes. Given the genetic findings in this rare tumor-type, we suggest that this case may be used as a model for understanding the development of biphenotypic neoplasia or intratumoral heterogeneity in some cases.

Multicenter case series of indolent small/medium-sized CD8+ lymphoid proliferations with predilection for the ear and face.

We report 7 cases of a CD8 lymphoid proliferation of the ear and face with a cytotoxic T-cell phenotype, but an indolent clinical course. All patients presented with stable or slowly growing asymptomatic lesions on the ear, nose, or lower eyelid. Histopathology showed a dense diffuse dermal infiltrate of small- to medium-sized atypical lymphocytes without destructive features. The lymphocytes were positive for CD3, CD8, ß-F1, and TIA-1 and negative for CD4, CD30, CD56, granzyme B, and PD-1. Of note, the proliferation index was low in available cases. All patients remained in complete remission at median follow-up of 14 months regardless of treatment modality. Staging was negative for extracutaneous disease in all patients. The clinically indolent behavior and histopathologic phenotype together with a low proliferation index (10%-15%) emphasize the importance of accurate diagnosis and appropriate clinical management to avoid overtreatment and complications of therapy.

The risk of rash associated with ipilimumab in patients with cancer: a systematic review of the literature and meta-analysis.

BACKGROUND: Ipilimumab is a human antibody that inhibits cytotoxic T-lymphocyte-associated antigen 4, leading to increases in T-cell activation and interleukin 2 secretion and has been approved for the treatment of advanced melanoma. Dermatologic adverse events such as rash, pruritus, and vitiligo have been reported in trials, with varying incidences. The overall incidence and risk of rash to ipilimumab is unknown. OBJECTIVE: We conducted a systematic review of the literature and performed a meta-analysis to ascertain the incidence and risk of developing rash among patients receiving ipilimumab. METHODS: Databases from PubMed and Web of Science from January 1998 until July 2011 and abstracts presented at the American Society of Clinical Oncology meetings from 2004 through 2011 were searched to identify relevant studies. The incidence and relative risk of rash were calculated using random effects or fixed effects model depending on the heterogeneity of included studies. RESULTS: A total of 1208 patients from clinical trials were included in this analysis. The overall incidence of all-grade rash was 24.3% (95% confidence interval [CI] 21.4%-27.6%), with a relative risk of 4.00 (95% CI 2.63-6.08, P < .001). The overall incidence of high-grade rash was 2.4% (95% CI 1.1%-5.1%), with a relative risk of 3.31 (95% CI 0.70-15.76, P = .13). LIMITATIONS: The ability to detect rash may vary among institutions. CONCLUSION: There is a significant risk of developing rash in patients with cancer receiving ipilimumab. There was no statistically significant difference in the risk of rash based on dose or underlying tumor. Adequate monitoring and early intervention are recommended to prevent decreased quality of life and inconsistent dosing.

A case-control study of clinicopathologic features, prognosis, and therapeutic responses in patients with granulomatous mycosis fungoides.

BACKGROUND: Granulomatous mycosis fungoides (GMF) is an uncommon variant of mycosis fungoides (MF). OBJECTIVE: We sought to analyze the relative frequency, clinicopathologic characteristics, prognosis, and therapeutic responses of GMF. METHODS: We conducted a retrospective case-control study of patients with GMF and age- and stage-matched patients with classic MF between 1981 and 2012. RESULTS: A total of 27 patients with GMF were identified, representing 6.3% of all patients with MF at our center. Skin manifestations were similar to classic MF having an atypical lichenoid CD4(+) CD8(-) lymphocytic infiltrate with interstitial histiocytes and/or perivascular granulomas with giant cells. Fewer patients with GMF achieved a partial response or complete response with topical (57% vs 83%; P = .002) or ultraviolet light (62% vs 90%; P = .006) therapy. The 5- and 10-year progression-free survival rates were significantly lower in patients with GMF (59% and 33%) compared with patients with classic MF (84% and 56%; P = .02), but overall survival was similar between groups (86% and 72% vs 85% and 85%; P = .54). LIMITATIONS: The retrospective methodology may underestimate the frequency of GMF. The median follow-up time may be too short to detect possible differences in overall survival. CONCLUSION: More frequent disease progression and poorer response to skin-directed therapies were observed in patients with GMF. Our findings may be helpful in selecting the most appropriate treatment for these patients.

CD30+ lymphomatoid drug reactions.

We report 5 cases of cutaneous CD30+ lymphomatoid drug reactions that occurred shortly after the onset of drug exposure and resolved promptly upon withdrawal of the offending agents. The cases showed protean dermatologic manifestations ranging from diffuse erythema with desquamation to macules, papules, and annular plaques. The suspect drugs were amlodipine (a calcium channel blocker) for 2 cases, sertraline (a selective serotonin reuptake inhibitor) for 1 case, gabapentin for 1 case, and levofloxacin (a fluoroquinolone) versus cefepime (a fourth generation cephalosporin), and metoprolol (a beta blocker), in the fifth case. The histopathologic findings included varying combinations of spongiotic dermatitis, lichenoid infiltrates, and interface dermatitis with a dermal infiltrate of large atypical lymphocytes. Three of the 5 cases contained as much as 30% CD30+ staining of all lymphocytes, whereas the remaining 2 showed 5%-15% positivity. Three patients had a history of allergy or immune dysregulation. Increased knowledge of CD30 positivity in lymphomatoid drug reactions may be relevant in an era of targeted drug therapies. Recognition of these findings may help clinicians to tailor appropriate clinical evaluation and treatment including a review of medications and the removal of possible offending agents.

Aggressive Cutaneous Lymphomas and Their Mimics.

Cutaneous lymphomas encompass a heterogeneous group of neoplasms with a wide spectrum of clinical presentations, histopathologic features, and prognosis. Because there are overlapping pathologic features among indolent and aggressive forms and with systemic lymphomas that involve the skin, clinicopathologic correlation is essential. Herein, the clinical and histopathologic features of aggressive cutaneous B- and T-cell lymphomas are reviewed. Indolent cutaneous lymphomas/lymphoproliferative disorders, systemic lymphomas, and reactive processes that may mimic these entities are also discussed. This article highlights distinctive clinical and histopathologic features, increases awareness of rare entities, and presents new and evolving developments in the field.