Multiple Keratoacanthoma-like Syndromes: Case Report and Literature Review.

Keratoacanthoma (KA) is a fast-growing skin tumor subtype that can be observed as a solitary lesion or rarely as multiple lesions in the context of rare genetic syndromes. Syndromes with multiple keratoacanthoma-like lesions have been documented as multiple self-healing squamous epithelioma (Ferguson-Smith syndrome), eruptive keratoacanthoma of Grzybowski, multiple familial keratoacanthoma of Witten and Zak Muir-Torre syndrome, and incontinentia pigmenti. The treatment approach of those entities is challenging due to the numerous lesions, the lesions' undefined nature, and the co-existence of other malignant skin tumors. Herein, we report a case of a 40-year-old woman who developed multiple treatment-resistant Ferguson-Smith-like keratoacanthomas with a co-existing large and ulcerated invasive squamous cell carcinoma and microcystic adnexal carcinoma on the scalp. Multiple keratoacanthomas on her extremities were successfully treated with oral acitretin (0.5 mg/kg/day) in combination with topical Fluorouracil (5-FU) 5%, while excision and plastic surgery restoration were performed to treat the ulcerated cancer lesion on her scalp. Due to the interesting nature of this rare syndrome, we performed a literature review including case reports and case series on multiple-KA-like lesions syndromes and focusing on diagnosis and therapy approaches. We also conducted a comparison of patient reports, which included assessing the clinical appearance of the lesions and evaluating the success and progress or the failure of various treatment approaches that were implemented.

Lichenoid drug eruption associated with imatinib mesylate therapy.

INTRODUCTION: Imatinib Mesylate (IM), a tyrosine kinase inhibitor, has been reported to cause several adverse reactions, most of them with cutaneous involvement. Non- Lichenoid IM associated skin reactions have been sufficiently- recorded. To our knowledge, Lichenoid Drug Eruption (LDE) is recorded in a minority of registries. CASE REPORT: To describe an LDE induced case by IM treatment. TREATMENT AND OUTCOME: Histological Confirmation and promptly dermatological consultation relieved successfully the cutaneous adverse event. DISCUSSION: Ongoing expansion of IM usage in a wide spectrum of new indications is more likely to make physicians experience such LDE cutaneous side effects more often. Hence, they should be highly suspicious to early detect these distinct histologic entities, handle these undesired complications and guarantee satisfactory immediate outcomes, avoiding frivolous IM dosage modifications.

Concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma in a patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma.

The phenomenon of histiocytic/dendritic cell sarcomas arising through transformation of a pre-existed lymphoproliferative disease is called transdifferentiation. Langerhans cell sarcoma transdifferentiating from chronic lymphocytic leukemia/small lymphocytic lymphoma is extremely rare and all the reported cases were localized in lymph nodes. We present a case of concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, in which the chronic lymphocytic leukemia/small lymphocytic lymphoma preceded the development of the Langerhans cell sarcoma. A cutaneous lesion from a 63-year-old patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma was biopsied. The histologic examination revealed a mixture of two cell populations infiltrating diffusely the dermis. The first was composed of small lymphoid cells with somewhat monotonous appearance and mild nuclear atypia positive for PAX5, CD79a, CD20, CD23, CD5, and LEF1. The second was composed of large cells with abundant cytoplasm and pleomorphic nuclei. These cells were positive for CD1a, CD207, and S100 protein and exhibited a high mitotic rate and a high MIB-1 immunostaining index. Therefore, two different entities, chronic lymphocytic leukemia/small lymphocytic lymphoma and Langerhans cell sarcoma, were detected in the same skin fragment. The patient died 3 years after initial diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma.

Another window into tumor microenvironment: a case of Β-cell rich folliculotropic mycosis fungoides responding to rituximab.

The role of tumor infiltrating immune cells in cancer development and progression is a new, promising field in oncological research. An increasing number of novel anti-cancer agents are focussing on the tumor microenvironment. Various studies have reported on B-cell infiltrates in mycosis fungoides (MF), but despite the substantial volume of interesting findings, solid evidence regarding their specific role in cancer is still vague. We present a case of tumor stage  MF responding to rituximab. We support the hypothesis that lymphoma-infltrating B-cells have a significant impact on cutaneous lymphoma course and seem to be both an important and effective therapeutic target. The reduction of B-cell population led to disease's overall remission, probably by restoring patient's immunologic tumor control.

Mediastinal debulking for a T-cell leukaemia/lymphoma presenting with cardiac tamponade.

Anterior mediastinal masses are relatively uncommon and include a wide variety of lesions. Lymphomas account for 25% of anterior mediastinal masses. Lymphomas and other haematological malignancies are associated with pericardial effusion. There are also cases where a cardiac tamponade occurred. The aim of the case reported herein is to discuss the surgical approach and particularly the mediastinal debulking as an adjunct to systematic treatment for haematological diseases presenting as an anterior mediastinal mass responsible for a cardiac tamponade.

Phototherapy as a first-line treatment for early-stage mycosis fungoides: The results of a large retrospective analysis.

BACKGROUND: Phototherapy is one of the main treatments for mycosis fungoides (MF). In this study, we analyzed the efficacy and safety of phototherapy as a first-line treatment in patients with early-stage disease. METHODS: We analyzed treatment outcomes in a group of 227 early-stage patients. The chi-squared test, the parametric t test, and ANOVA test and the non-parametric tests of Mann-Whitney and Kruskal-Wallis were applied for data analysis. RESULTS: 55.9% of patients treated with UVB-NB reached complete remission (CR), while analog rates after PUVA treatment were 74.5% (P = .015). Patients with patch-stage disease showed better response rates to PUVA compared to UVB-NB therapy (CRs 56.7% vs 91.3%, P < .001). Regarding the latter, long-lasting disease was proven as an independent negative prognostic factor for treatment outcome. Phototypes I and II were found to be favorable prognostic factors for patients treated with PUVA. Maintenance treatment did not alter final relapse rates but led to prolonged time to relapse compared to no-maintenance treated cases (19.5 months, vs 32.3, P < .002). CONCLUSION: Our analysis indicates that PUVA leads to better responses and longer relapse-free intervals both in patch- and plaque-stage disease. UVB-NB could be a valid therapeutic alternative for patients with recent disease presentation.

Multiple cutaneous reticulohistiocytosis with T-cell large granular lymphocyte clonopathy.

A 63-year-old Caucasian man presented with a 4-month history of disseminated asymptomatic reddish-brown papulonodular lesions. A skin biopsy showed dermal infiltration with CD68+ histiocytes, predominantly with eosinophilic cytoplasm, some with a ground-glass cytoplasm, and a small number of giant cells. The diagnosis of multiple cutaneous reticulohistiocytosis was made. Bone marrow immunophenotyping due to peripheral blood lymphocytosis revealed the presence of a monoclonal population of CD3+ , CD8+ CD57+ large granular lymphocytes. The present case suggests the coexistence of multiple cutaneous reticulohistiocytosis with an underlying disorder.

In situ assessment of PI3K and PTEN alterations in mycosis fungoides: correlation with clinicopathological features.

Deregulated signalling through phosphatidylinositol 3-kinase (PI3K) pathway plays a critical role in tumour initiation and progression. We have already shown that AKT is activated in skin lesions in Mycosis Fungoides (MF) and we herein further investigate the frequency and clinical significance of PTEN and PI3K at the protein and at the DNA level as well as the presence of AKT1 mutations in skin lesions from 50 patients with MF clinical stages I-IV in relation to clinicopathological features. Increased p-AKT expression correlated with poor prognosis in plaques (P = 0.0198), whereas p-AKT was an independent predictor of poor survival in the entire cohort (P = 0.017, HR = 1.012). PTEN cytoplasmic expression was found low or absent in all 77.3% of cases and inversely correlated with advanced clinical stages (P = 0.0744). Molecular analysis showed no AKT1 mutation, no PI3KCA copy number gain, only 1 case with PI3KCA mutation in exon 9 and 3 cases with PTEN mutations (7%) in exons 7, 8 and 5. The latter correlated with disease (P = 0.0253) and progression (P < 0.0001) free survival in tumour stage. Although activation of PI3K/AKT signalling pathway due to PTEN alterations is rarely attributed to abnormalities in PTEN, PI3K, and AKT1 genes, PTEN mutations exert a negative effect on patients' prognosis with tumours.

A comprehensive immunohistochemical approach of AKT/mTOR pathway and p-STAT3 in mycosis fungoides.

BACKGROUND: Although the expression pattern of phosphorylated (p)-mTOR pathway components has attracted scientific interest in several neoplasms, to our knowledge, there is no published information regarding its significance in mycosis fungoides (MF). OBJECTIVE: We sought to perform a comprehensive simultaneous assessment of key members of AKT/mTOR pathway along with p-extracellular signal-regulated kinase (ERK), NOTCH1, and p-STAT3 in patients with MF. METHODS: In all, 54 skin biopsy specimens (21 tumors, 30 plaques, and 3 folliculotropic MF) from 50 patients with MF were analyzed immunohistochemically for p-mTOR, its upstream p-AKT, its downstream effectors p-p70S6K and p-4E-BP1, and for p-ERK1/2, NOTCH1, and p-STAT3. RESULTS: p-mTOR was coexpressed with p-p70S6K in 67.3% of lesions, but coexpression with other molecules was less common. p-p70S6K and marginally NOTCH1 displayed higher H-scores in tumors than in plaques. Significant correlations were recorded between p-ERK and p-4E-BP1, as well as between NOTCH1 and p-p70S6K or p-4E-BP1. NOTCH1, p-4E-BP1, and p-p70S6K expression were associated with advanced stage. In survival analysis simultaneous overexpression of p-AKT and p-p70S6K, along with p-4E-BP1 positivity, adversely affected cancer-specific, disease-free, and progression-free survival in advanced-stage cases. LIMITATIONS: A limitation may be the small number of cases included in our investigation, precluding multivariate survival analysis. CONCLUSIONS: Activation of AKT/mTOR pathway in MF appears to be correlated with NOTCH1, p-ERK, and p-STAT3 and is implicated in the acquisition of a more aggressive phenotype. The combination of p-AKT, p-p70S6K, and p-4E-BP1 emerges as a significant potential prognostic marker in patients with advanced stage.

Wells Syndrome with Generalized Oedema.

Wells syndrome or eosinophilic cellulitis is a rare and relapsing skin disease which lacks systemic involvement. A skin biopsy is needed to establish a diagnosis. Several precipitating factors have been proposed but no proven causative link has been found. On the other hand, Churg-Strauss syndrome, also known as eosinophilic granulomatosis with polyangiitis (EGPA), an auto-immune disease, is associated with multiorgan, including cutaneous manifestations. We report a case with overlapping features of Wells and Churg-Strauss syndrome, suggesting that these syndromes could be part of the same nosological entity. LEARNING POINTS: Biopsies are essential to establish a diagnosis in unusual cases of cellulitis.COVID-19 vaccination is a putative trigger for Wells syndrome.There is significant overlap between Wells and Churg-Strauss syndromes.

Primary follicular lymphoma of the uterine cervix: A case report.

Primary non-Hodgkin lymphoma of the uterine cervix is a rare clinical entity. The present case report describes an incidence of primary cervical follicular lymphoma, diagnosed during management of concurrent cervical intraepithelial neoplasia. The present case report outlines not only the necessity of adhering to guidelines regarding the management of abnormal cervical cytology, but also the importance of expert pathological review and the need for personalized management.

Cutaneous B-cell Pseudolymphoma: A Rare Case Masquerading a Thoracic Mass in a Fourteen-Year-Old Male Patient.

Cutaneous B-cell pseudolymphoma (CBPL) may appear in the face, chest, or upper limbs, and it can be asymptomatic or in the form of nodules, papules, or masses. In most cases, it is idiopathic. However, some causes that have been identified are trauma, contact dermatitis, injected vaccinations, bacterial infections, tattoo dyes, insect bites, and certain drugs. Since the histology and clinical presentation of cutaneous pseudolymphoma (CPSL) are similar to those of cutaneous lymphomas, the diagnosis is usually based on an incisional or excisional biopsy. In this paper, a 14-year-old male patient with a two-month-old mass in the right lateral thoracic region is taken as a case study. He had neither symptoms, nor a past medical history, nor a family history. He had an insect bite a month ago and was fully vaccinated. However, the mass was some centimeters away from the insect bite. A biopsy was taken. The products of it were two paraffin cubes and two histological slides (H&E). The diagnosis was cutaneous B-cell pseudolymphoma. The total removal of the mass was decided since, in idiopathic cases like this, CBPL is not usually healed with topical and non-invasive treatments. Follow-up examinations were suggested since a further antigenic reaction is possible. If cutaneous B-pseudolymphoma is early diagnosed and treated, it does not cause serious problems. In some cases, it even resolves on its own.

Epidemiological trends in cutaneous lymphomas in Greece.

Primary cutaneous lymphomas (PCLs) are a heterogenous group of non-Hodgkin lymphomas arising in the skin from T- or B-lymphocytes, for which there is limited epidemiological data available. To describe the disease characteristics and estimate annual incidence rates (IRs) and temporal trends of PCLs and their subtypes in Attica, Greece. A retrospective analysis of all PCL patients, diagnosed in Attica's main haemopathology referral centre from 2009 to 2021, was conducted. In total, 1,189 patients were included; 725 males and 464 females (males__females=1.56). The median age at diagnosis was 62 years. The annual IR was 2.2 new cases per 100,000 individuals. Most patients (n=979, 82.3%) were diagnosed with cutaneous T-cell lymphoma (CTCL) with a crude IR of 1.8 new cases per 100,000 person-years. Mycosis fungoides (MF) was the most common subtype (n=817, 68.7%), followed by lymphomatoid papulosis (LyP) (n=59, 5.0%). The crude IR for MF was 1.5 new cases per 100,000 person-years. Cutaneous B-cell lymphomas (CBCLs) accounted for 17.6% (n=210) of all PCLs (IR: 0.4 new cases per 100,000 person-years). PCL, CTCL and MF incidence rates increased from 2009 to 2019, followed by a decrease in 2020-2021. The incidence rate of CBCL increased steadily during the study period. The annual IRs of PCL in Greece were higher than those reported in other studies from Europe, America and Asia. The increase in IRs from 2009 to 2019 may reflect physicians' improved diagnostic efficiency. The COVID-19 pandemic may be the reason for the decline in PCL, CTCL and MF diagnoses from 2020 to 2021.

Case Report: Malignant melanoma in a patient with Crohn's disease treated with ustekinumab.

The cornerstone of inflammatory bowel disease (IBD) treatment is immunomodulators. IBD patients are at increased risk of intestinal and extraintestinal malignancy. Ustekinumab is a fully humanized monoclonal anti-IL12/23 antibody with a good safety profile. Malignancies of breast, colon, head and neck, kidney, prostate, thyroid, and non-melanoma skin cancer have been reported among patients who received ustekinumab. We report the case of a 42-year-old Crohn's patient on long-term treatment with ustekinumab, who developed achromatic malignant melanoma. Crohn's was diagnosed at the age of 15, with upper and lower gastrointestinal involvement and was initially treated with azathioprine (2mg/kg for 4 years) and infliximab (5mg/kg for 6 weeks). Due to ileal obstruction, the patient underwent stricturoplasty and received adalimumab (40mg every other week) for two years. He then discontinued therapy and a year later underwent right hemicolectomy. Adalimumab was reinstituted (40mg every other week) and the patient remained in clinical remission for two years. His overall exposure to adalimumab was four years. Ustekinumab was initiated due to a relapse and after 3 years, an incident of scalp itching led to the diagnosis metastatic achromatic malignant melanoma bearing BRAF V600E mutation. He received targeted therapy with an initial good response. We aim to point out the risk of dermatologic malignancy in IBD patients on long-term immunosuppression and the lifelong and meticulous evaluation that is required.

Primary renal MALT lymphoma presenting with cryoglobulinaemia.

Primary renal lymphoma is a rare clinicopathologic entity that typically presents as renal mass or renal impairment with enlarged kidneys. We describe the case of a 66-year-old woman who presented with type II mixed cryoglobulinaemic vasculitis as the first manifestation of underlying low-grade primary renal lymphoma.

Chlormethine Gel in Combination with Other Therapies in the Treatment of Patients with Mycosis Fungoides Cutaneous T Cell Lymphoma: Three Case Reports.

INTRODUCTION: Chlormethine gel is a skin-directed therapy recommended for patients with early-stage mycosis fungoides (MF) cutaneous T cell lymphoma. METHODS: Herein, we present three cases of patients with stage IB-IIB MF who were treated with chlormethine gel and concomitant therapies. RESULTS: All patients responded well to treatment with chlormethine gel; complete responses were observed with improvements in Modified Severity-Weighted Assessment Tool scores and severity of lesions; one patient reported an improvement in quality of life. While adverse events did occur after treatment initiation, they were skin related and could be effectively managed through reductions in treatment frequency and the addition of emollients and topical steroids. CONCLUSION: The cases presented here illustrate that chlormethine gel is an effective and safe treatment option for patients with MF who had received prior therapies that had proved ineffective. Chlormethine gel could be combined with other skin-directed or systemic therapies for optimal benefit. Incidences of dermatitis were seen to be successfully managed and quality of life benefits were also reported.