Dermoscopic spectrum of mycosis fungoides: a retrospective observational study by the International Dermoscopy Society.

BACKGROUND: The dermoscopic features of classic patch stage mycosis fungoides (MF) have been described, but data on plaque and tumoral stage as well as rarer MF subtypes is limited. OBJECTIVE: To evaluate dermoscopic morphology and dermoscopic-pathological correlations of classic MF stages and investigate dermoscopic features of MF variants. METHODS: Patients with histopathologically confirmed lesions of classic MF (patch, plaque and tumoral stage) or folliculotropic, erythrodermic and poikilodermatous MF were included. Standardized evaluation of dermoscopic pictures of the included MF variants and comparative analysis and dermoscopic-pathological correlation assessment of different stages of classic MF were performed. RESULTS: A total of 118 instances were included (75 classic MF, 26 folliculotropic MF, 9 erythrodermic MF and 8 poikilodermatous MF). Linear/linear-curved vessels and white scales in the skin furrows were significantly associated with patch-stage MF, while clustered dotted vessels were related to plaque-stage MF and peripheral linear vessels with branches, ulceration and red globules separated by white lines to tumour-stage MF. Moreover, patchy white scales were significantly more common in patches and plaques compared to tumours, whereas focal bright white structureless areas were related to plaque and tumoral stage. Vessels histopathologically corresponded to dilated vascular structures in the dermis, orange structureless areas to either dermal hemosiderin (patch/plaque stage) or dense cellular infiltration (tumours), bright white lines/structureless areas to dermal fibrosis and ulceration to loss of epidermis. The main dermoscopic findings of folliculotropic MF were lack of hairs, dilated follicles and follicular plugs, while erythrodermic MF was mainly characterized by linear/dotted vessels, patchy white scales and focal orange structureless areas and poikilodermatous MF by focal white and brown structureless areas, white patchy scales and brown reticular lines. CONCLUSION: Dermoscopy may allow a more precise characterization of classic MF and reveal clues suggestive of the main MF variants.

Outpatient dermatology consultations for oncology patients with acute dermatologic adverse events impact anticancer therapy interruption: a retrospective study.

BACKGROUND: Dermatologic adverse events (dAEs) of anticancer therapies may negatively impact dosing and quality of life. While therapy interruption patterns due to dAEs have been studied in hospitalized cancer patients, similar outcomes in outpatient oncodermatology are lacking. OBJECTIVES: To analyse the therapy interruption patterns, clinico-histopathologic characteristics and management outcomes of outpatient dermatology consultations for acute dAEs attributed to the most frequently interrupted class of oncologic agents. METHODS: We performed a retrospective cohort study of all cancer patients who received a same-day outpatient dermatology consultation for acute dAEs at our institution from 1 January to 30 June 2015. Relevant data were abstracted from electronic medical records, including demographics, oncologic history and explicit recommendations by both the referring clinician and consulting dermatologist on anticancer therapy interruption. Consultations with the most frequently interrupted class of oncologic treatment were characterized according to clinico-histopathologic features, dermatologic management and clinical outcomes. RESULTS: There were 426 same-day outpatient dermatology consultations (median age 59, 60% female, 30% breast cancer), of which 295 (69%) had systemic anticancer therapy administered within 30 days prior. There was weak inter-rater agreement between referring clinicians and consulting dermatologists on interruption of anticancer treatment (n = 150, κ = 0.096; 95% CI -0.02 to 0.21). Seventy-three (25%) consultations involved interruption by the referring clinician, most commonly targeted therapy (24, 33%). Maculopapular rash was commonly observed in 23 consultations with 25 dAEs attributed to targeted agents (48%), and topical corticosteroids were most frequently utilized for management (22, 38%). The majority (83%) of consultations with targeted therapy-induced dAEs responded to dermatologic treatment and 84% resumed oncologic therapy, although three (19%) at a reduced dose. Rash recurred only in two instances (13%). CONCLUSIONS: A high frequency of positive outcomes in the management of targeted therapy-induced dAEs by outpatient consulting dermatologists and low recurrence of skin toxicity suggests impactful reductions in interruption of anticancer therapy.

Survival, disease progression and prognostic factors in elderly patients with mycosis fungoides and Sézary syndrome: a retrospective analysis of 174 patients.

BACKGROUND: Advanced age at diagnosis is considered a poor prognostic factor in mycosis fungoides (MF) and Sézary syndrome (SS). OBJECTIVE: To evaluate the outcomes and prognostic factors in patients diagnosed at an advanced age (≥65 years) with MF/SS. METHODS: Survival, progression rates and various clinical and histopathological variables were studied in a group of 174 elderly patients diagnosed with MF/SS between 1992 and 2015 at a single referral cancer center in the United States. Kaplan-Meier estimates were used to determine survival and progression and Cox proportional hazards regression univariate and multivariate models were used to identify prognostic factors. RESULTS: Of 174 elderly patients, 76.4% were diagnosed with early-stage (clinical stages IA-IIA) and 23.6% with late-stage MF/SS (IIB-IV). Advanced age was associated with poor overall survival, but not with disease-specific survival (DSS) or progression-free survival (PFS). Gender, increasing clinical stage, T and B classifications, elevated lactate dehydrogenase (LDH) levels and development of large cell transformation (LCT) were significant predictors of poor survival or disease progression. Patients with early-stage MF and <10% total skin involvement (T1 classification) or patch-only disease (T1a/T2a) showed better PFS with no observed disease-specific mortality. Folliculotropic MF was associated with poor DSS in patients with early-stage disease. CONCLUSIONS: Older age at diagnosis of MF/SS does not predict worse disease-specific outcomes. Elderly patients with early-stage disease, specifically involving less than 10% of the skin surface with patches but without plaques or folliculotropism, have an excellent prognosis. However, the development of LCT is a strong prognostic indicator of poor survival in elderly patients with MF/SS.

Acneiform follicular mucinosis: an indolent follicular mucinosis variant unrelated to mycosis fungoides?

Follicular mucinosis (FM) can present as an acneiform eruption, and is usually a benign variant of primary FM unrelated to cutaneous T-cell lymphoma (CTCL). We report two cases of women in their twenties who presented with an acneiform rash on the face, arms and back. In both cases, pathological evaluation of the facial papules revealed predominantly mucinous degeneration of the follicular epithelium, with insufficient lymphocytic infiltration or atypia to diagnose mycosis fungoides. These cases are similar to previous reports of acneiform FM. As none of the reported cases progressed to CTCL, we consider that overdiagnosis and overtreatment should be avoided in acneiform FM, but recommend long-term follow-up.

Dermoscopy and the diagnosis of primary cutaneous B-cell lymphoma.

BACKGROUND: Primary cutaneous B-cell lymphomas (PCBCLs) are frequently misdiagnosed, and a biopsy is needed to attain the correct diagnosis. OBJECTIVE: To characterize the dermoscopic features of PCBCL. METHODS: In this retrospective observational study, we analysed the pathology reports of 172 newly diagnosed PCBCL for the initial clinical differential diagnosis. The dermoscopic images of 58 PCBCL were evaluated for dermoscopic features. Two dermoscopy experts, who were blinded to the diagnosis and the study objective, evaluated images from 17 cases for a dermoscopic differential diagnosis. RESULTS: Of 172 biopsy-proven PCBCL lesions, cutaneous lymphoma was suspected by the clinician in 16.3%; the leading diagnosis was basal cell carcinoma in 17.4%, and other skin neoplasms in 21%. Studying 58 PCBCL dermoscopic images, we most frequently identified salmon-coloured background/area (79.3%) and prominent blood vessels (77.6%), mostly of serpentine (linear-irregular) morphology (67.2%). Dermoscopic features did not differ significantly by subtype or location. Blinded evaluation by dermoscopy experts raised a wide differential diagnosis including PCBCL, arthropod bite, basal cell carcinoma, amelanotic melanoma and scar/keloid. CONCLUSIONS: Two dermoscopic features, salmon-coloured area/background and serpentine vessels, are frequently seen in PCBCL lesions. These characteristic dermoscopic features, although not specific, can suggest a possible diagnosis of PCBCL.

Final results of phase II trial of doxorubicin HCl liposome injection followed by bexarotene in advanced cutaneous T-cell lymphoma.

BACKGROUND: High response rates for doxorubicin HCl liposome injection (DLI) in cutaneous T-cell lymphoma (CTCL) have been reported with vague criteria until recently. Approximately 50% of CTCL patients respond to bexarotene (Bex). PATIENTS AND METHODS: A phase II trial was carried out to clarify the true overall response rate (ORR) for DLI and to assess the role of sequential Bex. Patients were treated with DLI 20 mg/m(2) i.v. every 2 weeks for 16 weeks (8 doses) followed by 16 weeks with Bex 300 mg/m(2) orally. Response assessments were carried out after 16 (DLI) and 32 weeks (Bex). Skin responses were measured by the modified Severity-Weighted Assessment Tool (mSWAT) and the Composite Assessment of Index Lesion Severity (CA). RESULTS: Thirty-seven patients were treated: stage IV (22, 8 with Sézary syndrome), IIB (10), earlier stage refractory to skin-directed therapies or radiation therapy (5). For 34 assessable patients: ORR 14/34 [41%: partial response (PR) 12, clinical complete response (CCR) 2]. Maximum responses were all seen after 16 weeks DLI. Median progression-free survival (PFS) was 5 months. There were 22 deaths: 21 of disease and 1 of heart failure. Twenty-seven grade 3 and 5 grade 4 toxic events were observed. CONCLUSION(S): With strict criteria, DLI ORR is among the highest reported for single agents in CTCL. Sequential Bex did not increase the response rate or duration.

Post-reconstruction dermatitis of the breast.

BACKGROUND: Approximately one-third of women diagnosed with breast cancer undergo mastectomy with subsequent implant-based or autogenous tissue-based reconstruction. Potential complications include infection, capsular contracture, and leak or rupture of implants with necessity for explantation. Skin rashes are infrequently described complications of patients who undergo mastectomy with or without reconstruction. METHODS: A retrospective analysis of breast cancer patients referred to the Dermatology Service for diagnosis and management of a rash post-mastectomy and expander or implant placement or transverse rectus abdominis myocutaneous (TRAM) flap reconstruction was performed. Parameters studied included reconstruction types, time to onset, clinical presentation, associated symptoms, results of microbiologic studies, management, and outcome. RESULTS: We describe 21 patients who developed a rash on the skin overlying a breast reconstruction. Average time to onset was 25.7 months after expander placement or TRAM flap reconstruction. Clinical presentations included macules and papules or scaly, erythematous patches and plaques. Five patients had cultures of the rash, which were all negative. Skin biopsy was relatively contraindicated in areas of skin tension, and was reserved for non-responding eruptions. Treatments included topical corticosteroids and topical antibiotics, which resulted in complete or partial responses in all patients with documented follow-ups. CONCLUSION: Our findings suggest that tension and post-surgical factors play a causal role in this hitherto undescribed entity: "post-reconstruction dermatitis of the breast." This is a manageable condition that develops weeks to years following breast reconstruction. Topical corticosteroids and antibiotics result in restoration of skin barrier integrity and decreased secondary infection.

Spectrum of Kaposi's sarcoma in the epidemic of AIDS.

Kaposi's sarcoma (KS) is seen with increased frequency in the course of the epidemic of acquired immune deficiency syndrome. In this population, KS has manifested in an aggressive and more disseminated fashion as compared to the classical type. As the epidemic of acquired immune deficiency syndrome continues to spread and more cases of KS are evaluated, a distinct diversity in the clinical presentation and in the course of the disease as well as in variation in the prognosis and response to therapy is being observed. A preliminary description of the spectrum of KS in the epidemic of acquired immune deficiency syndrome is presented here.

Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results.

PURPOSE: Cutaneous T-cell lymphomas (CTCL) are malignancies of T cells appearing as skin lesions and are responsive to retinoid therapy. Safety and efficacy of a novel RXR-selective retinoid (rexinoid) bexarotene (Targretin, LGD1069; Ligand Pharmaceuticals Inc, San Diego, CA) was evaluated as a single-agent oral therapy administered once daily in an open-label study in patients with refractory advanced-stage CTCL. PATIENTS AND METHODS: Ninety-four patients with biopsy-confirmed CTCL in advanced stages (IIB-IVB) were enrolled at 26 centers. Fifty-six patients received an initial dose of 300 mg/m2/d oral bexarotene and 38 started at more than 300 mg/m2/d. RESULTS: Clinical complete and partial responses were reported by Primary End point Classification for the study in 45% (25 of 56) of patients enrolled at 300 mg/m2/d dosing. At more than 300 mg/m2/d, 55% (21 of 38) of patients responded, including 13% (five of 38) clinical complete. For the 300 mg/m2/d initial dose group, the rate of relapse after response was 36% and the projected median duration of response was 299 days. Improvements were also seen in overall body-surface area involvement, median index lesion surface area, adenopathy, cutaneous tumors, pruritus, and CTCL-specific quality of life. The most frequent drug-related adverse events included hypertriglyceridemia (associated rarely with pancreatitis), hypercholesterolemia, hypothyroidism, and headache. CONCLUSION: Bexarotene is the first in a novel class of pharmacologic agents, the RXR-selective retinoids, or rexinoids. Bexarotene is orally administered, safe, and generally well tolerated with reversible side effects, and is effective for the treatment of advanced, refractory CTCL.

Association of HLA-DR5 with mycosis fungoides.

Mycosis fungoides (MF) and Sézary syndrome (SS) are uncommon neoplasms of the lymphoreticular system with distinct clinical, histologic, and immunologic features. Based on the thymus-derived nature of the neoplastic cells, MF and SS are both classified as cutaneous T-cell lymphoma. While substantially greater understanding of MF and SS has been made possible, the exact mechanism for the initiation of either disease is still unknown. The possible involvement of environmental factors as well as viral etiology, i.e., retroviruses, has been suggested. In order to investigate the possible role of HLA-associated variations in genetic susceptibility, 74 patients with histologically documented MF were typed for HLA-A, -B, and -C antigens. Half of these patients were also typed for HLA-DR antigens. An increase in DR5 was the only statistically significant deviation in HLA antigen frequencies in these patients (53% in MF as compared with 20% in controls). An increased frequency of HLA-DR5 has also been associated with scleroderma and juvenile rheumatoid arthritis both of which have immunologic alterations. Also HLA-DR5 has been associated with renal cell carcinoma and Kaposi's sarcoma. The association of MF with DR5 suggests that some individuals with the DR5 antigen may be at higher risk for virally initiated and/or neoplastic diseases possibly through an HLA-linked defect in the immune system.

Outbreak of Kaposi's sarcoma with cytomegalovirus infection in young homosexual men.

Kaposi's sarcoma, a multicentric malignant neoplasm, occurs in certain geographic areas in the world. It is most common in Equatorial Africa and Eastern Europe. The annual incidence of Kaposi's sarcoma in the United States is between 0.021 and 0.061 per 100,000 persons. The appearance of an outbreak of Kaposi's sarcoma in young homosexual men in New York and California is a new and unique phenomenon. Certain differences are already recognized between the disease in these young men and the ordinary Kaposi's sarcoma. Herein we report our observations of the first 10 cases of Kaposi's sarcoma in young homosexual men. In these patients, the disease follows an aggressive clinical course characterized by widespread skin lesions with early involvement of the lymph nodes. In some of these patients, the result was death in a short period of time after initial diagnosis. In addition, cytomegalovirus infections were seen in these patients, which suggests at least a possible association between this viral and the disease.

Analysis of T cell subsets in different clinical subgroups of patients with the acquired immune deficiency syndrome. Comparison with the "classic" form of Kaposi's sarcoma.

Ninety patients were grouped according to three different forms of acquired immune deficiency syndrome (AIDS): Kaposi's sarcoma "recent outbreak" type (38), reactive lymphadenopathy (27), and opportunistic infections (17), and a fourth group of patients with "classic" Kaposi's sarcoma (8). All patients with "classic" Kaposi's sarcoma were previously treated with electron-beam irradiation. These four groups were compared with 40 normal control subjects. Peripheral blood mononuclear cells isolated by density separation were reacted with a panel of mouse monoclonal antibodies that recognizes all peripheral blood T cells (OKT3-positive), helper (OKT4-positive), and suppressor (OKT8-positive) T cell subsets. The OKT4/OKT8 ratio was used to define the balance between these two subsets. All three groups with AIDS with or without Kaposi's sarcoma showed a decrease in the OKT4/OKT8 ratio. The group with "classic" Kaposi's sarcoma showed individual T cell subset values that were also abnormal. These findings confirm the previously reported imbalance of T cell subsets in patients with AIDS and Kaposi's sarcoma, which is also evident in patients with treated "classic" Kaposi's sarcoma.

Pulmonary Kaposi's sarcoma in the acquired immune deficiency syndrome. Clinical, radiographic, and pathologic manifestations.

Pulmonary Kaposi's sarcoma related to the acquired immune deficiency syndrome (AIDS) has not been well characterized. To define the clinical, radiographic, and pathologic features of this entity, 11 autopsy-proved cases of pulmonary Kaposi's sarcoma were reviewed. The most common clinical symptoms were dyspnea and cough, but hemoptysis and stridor were also found. Nodular infiltrates and pleural effusions were the most commonly found radiographic abnormalities. Pulmonary function tests were sensitive in detecting the pulmonary abnormalities due to Kaposi's sarcoma. A low diffusion capacity, lack of arterial desaturation with exercise, and obstruction to airflow were suggestive of pulmonary involvement with this malignancy. Although endobronchial Kaposi's sarcoma was visualized at bronchoscopy as cherry-red, slightly raised lesions, bronchial biopsy specimens always showed no abnormalities. Transbronchial brushings and biopsy specimens and analysis of pleural fluid were also not helpful in establishing a diagnosis. In the seven subjects with extensive parenchymal Kaposi's sarcoma at autopsy, the pleura was always involved. Eight subjects had involvement of the tracheobronchial tree. In all of the subjects, pulmonary Kaposi's sarcoma was a significant cause of morbidity, and in three of 11 subjects (27 percent) it was the direct cause of death.

Breast cellulitis after conservative surgery and radiotherapy.

PURPOSE: Cellulitis is a previously unreported complication of conservative surgery and radiation therapy for early stage breast cancer. Patients who presented with breast cellulitis after conservative therapy are described. METHODS AND MATERIALS: Eleven patients that developed cellulitis of the breast over a 38-month period of observation are the subject of this report. Clinical characteristics of patients with cellulitis and their treatment and outcome are reported. Potential patient and treatment-related correlates for the development of cellulitis are analyzed. RESULTS: The risk of cellulitis persists years after initial breast cancer therapy. The clinical course of our patients was variable: some patients required aggressive, long-duration antibiotic therapy, while others had rapid resolution with antibiotics. Three patients suffered from multiple episodes of cellulitis. CONCLUSION: Patients with breast cancer treated with conservative surgery and radiotherapy are at risk for breast cellulitis. Systematic characterization of cases of cellulitis may provide insight into diagnosis, prevention, and more effective therapy for this uncommon complication.

Histologic reactions to cutaneous infections by Mycobacterium haemophilum.

Mycobacterium haemophilum is an emerging pathogen in immunocompromised patients. We report the clinical and histologic findings of 16 skin biopsies from 11 patients with culture-proven infections by M. haemophilum. The patients had leukemia or non-Hodgkin's lymphoma. Ten of them had undergone bone marrow transplantation. When the skin biopsy specimens were taken, a portion of the skin was simultaneously submitted to a microbiology laboratory for cultures. The remaining skin was processed routinely. Acid-fast bacilli were found in 11 of 16 lesions. The number of histologically detectable organisms was typically low: nine biopsies had fewer than three bacilli per 50 oil immersion fields. The most common histologic pattern was a mixed suppurative and granulomatous reaction (7 of 16 biopsies). Four biopsies showed well-formed epithelioid granulomas. Two showed necrosis, one of which was ulcerated. One lesion was a subcutaneous abscess. Two biopsies showed a mixed lichenoid and granulomatous dermatitis. In one of them, the granulomatous reaction was focal and small. One biopsy lacked a granulomatous tissue reaction altogether; it showed an interface dermatitis, a perivascular and periadnexal lymphocytic infiltrate, and necrotizing lymphocytic small vessel vasculitis. A subsequent biopsy from the same patient additionally showed a focal granulomatous reaction. Our observation that infections by M. haemophilum can present with nongranulomatous or pauci-granulomatous reactions without necrosis is of note. Failure to suspect mycobacterial infection in such reactions contributes to probable underreporting of M. haemophilum and to misdiagnoses. Furthermore, our findings emphasize the importance of simultaneous biopsies for culture and histology in immunocompromised patients.

Histologic predictors of survival in acquired immunodeficiency syndrome-associated Kaposi's sarcoma.

The relationship between 22 histologic variables and survival was investigated in 93 patients with acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). All the patients were homosexual men in whom KS was the initial manifestation of AIDS. All patients were followed for at least 12 months or until death. Histologic specimens of the initial KS biopsy were reviewed in a blind manner by two of the authors and were evaluated for the presence of a number of histologic features. In a univariate analysis nodular lesions of KS (upsilon patch or plaque lesions), the absence of hemosiderin, the absence of irregular vascular spaces, and the presence of spindle cell nodules were all significantly associated with increased length of survival. Two variables previously shown to be related to survival (CD4:CD8 cell ratio, initial lesion on lower extremities) were included in a multivariate analysis (Cox model) in addition to the histologic variables. Complete data were available from 85 patients. In the multivariate analysis a higher helper to suppressor T-cell ratio, initial lesion on lower extremities, presence of spindle cell nodules, and nodular histology (upsilon patch or plaque histology) were all significantly associated with increased length of survival. These data suggest that in AIDS-associated KS, as in reticuloendothelial neoplasms, histologic features may be useful in identifying prognostically different subgroups of patients.

Granulocytic sarcoma. A new finding in the setting of preleukemia.

Preleukemia is a well-defined syndrome of hematopoietic dysfunction that may antedate the development of acute myelogenous leukemia. Granulocytic sarcoma refers to neoplastic infiltration in the skin, composed of immature cells of the granulocyte series. We report two cases of granulocytic sarcoma in the setting of preleukemia. The clinical importance of these cases, as well as the cutaneous manifestations of leukemia and the clinical spectrum of granulocytic sarcoma, are presented.

Topical treatment of cutaneous lesions of acquired immunodeficiency syndrome-related Kaposi sarcoma using alitretinoin gel: results of phase 1 and 2 trials.

OBJECTIVE: To evaluate the efficacy and safety of topical alitretinoin gel (9-cis-retinoic acid [LGD1057], Panretin gel; Ligand Pharmaceuticals, Inc, San Diego, Calif) in cutaneous Kaposi sarcoma (KS). DESIGN: Open-label, within-patient, controlled, dose-escalating phase 1 and 2 clinical trials. In all patients, 1 or more cutaneous KS lesions were treated with alitretinoin gel, and at least 2 other lesions served as untreated controls for up to 16 weeks. Alitretinoin (0.05% or 0.1% gel) was applied twice daily for the first 2 weeks and up to 4 times daily thereafter, if tolerated. SETTING: Nine academic clinical centers. PATIENTS: One hundred fifteen patients with biopsy-proven acquired immunodeficiency syndrome (AIDS)-related KS. MAIN OUTCOME MEASURES: AIDS Clinical Trials Group response criteria. RESULTS: Statistically significant clinical responses were observed in 31 (27%) of 115 patients for the group of treated index lesions compared with 13 (11%) for the group of untreated control lesions (P<.001). Responses occurred with low CD4(+) lymphocyte counts (<200 cells/microL) and in some patients with refractory response to previous systemic anti-KS therapy. The incidence of disease progression was significantly lower for treated index lesions compared with untreated control lesions (39/115 [34%] vs 53/115 [46%]; P =.02). Alitretinoin gel generally was well tolerated, with 90% of treatment-related adverse events confined to the application site and only mild or moderate in severity. CONCLUSIONS: Alitretinoin gel has significant antitumor activity as a topical treatment for AIDS-related KS lesions, substantially reduces the incidence of disease progression in treated lesions, and is generally well tolerated.