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.

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.

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.

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.

Case Report: Diagnosis of Myelodysplastic Syndrome in a 72-Year-Old Female With Interstitial Lung Disease.

Acute fibrinous and organizing pneumonia (AFOP) is an entity that can be secondary to various conditions leading to lung injury, such as infections, malignancies, and various autoimmune conditions or idiopathic interstitial lung disease, when no obvious underlying cause is identified. Myelodysplastic syndromes (MDS), on the other hand, are a spectrum of clonal myeloid disorders, with a higher risk of acute leukemia, characterized by ineffective bone marrow (BM) hematopoiesis and, thus, peripheral blood (PB) cytopenias. Immune deregulation is thought to take part in the pathophysiology of the disease, including abnormal T and/or B cell responses, innate immunity, and cytokine expression. In the literature, there are a few case reports of patients with MDS that have presented pulmonary infiltrates and were diagnosed as having AFOP or organizing pneumonia (OP). It is rare, though, to have isolated pulmonary infiltrates without Sweet's syndrome or even the pulmonary infiltrates to precede the diagnosis and treatment of MDS, which was our case. We present a 72-year-old female developing new lung infiltrates refractory to antibiotic treatment that responded well to corticosteroids and was histologically described as having OP. The treatment was gradually successfully switched to mycophenolate mofetil (MMF). The patient was later diagnosed with MDS. This interesting case report suggests firstly that a diagnosis of AFOP or OP should alert the clinician to search for an underlying cause including MDS and vice versa, the use of systemic steroids should not be postponed, and, finally, that MMF can successfully be used in these patients.

Clinical significance of PD-1 and PD-L1 molecules in patients with diffuse large B-cell lymphoma, not otherwise specified: Correlation with clinical and pathological findings.

PURPOSE: To investigate a possible chemorefractoriness mechanism of a Diffuse Large B-Cell Lymphoma (DLBCL) histological subtype, specifically of DLBCL, not otherwise specified (DLBCL, NOS), namely the effect of programmed cell death-1 (PD-1) immunoreceptor signalling, considering that the identification of additional negative prognostic factors can lead to better prognostication and therapeutic approaches. METHODS: We conducted a retrospective study of DLBCL, NOS patients, gathering their clinical features and combining them with PD-1 and its ligand (PD-L1) expression at the time of diagnosis as well as their response to treatment. RESULTS: No statistically significant difference was found when comparing PD-L1 positive to PD-L1 negative patients, while overall survival (OS) and duration of complete response (CR) were better for PD-L1 negative patients but the difference was not statistically significant. CONCLUSIONS: PD-L1 expression was not found to have any prognostic value for our cohort of DLBCL, NOS patients. What is more, the number of PD-1 positive tumour infiltrating lymphocytes was not associated with PD-L1 expression neither on malignant nor on non-malignant cells.

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.

Primary cutaneous follicle center lymphoma of the breast: Management of an exceedingly rare malignancy.

Primary cutaneous follicle center lymphoma (PCFCL) is defined as a low-grade B-cell non- Hodgkins lymphoma, which primarily occurs and remains confined to the skin, without evidence of extracutaneous or systemic involvement at the time of diagnosis. PCFCL affecting the breast skin is an exceedingly rare entity with only two cases reported in the English literature. We present a case of PCFCL affecting the periareolar breast skin and review the relevant literature. Our patient was a 64-year-old female who presented with an erythematous plaque in the periareolar region of the left breast. The diagnosis of PCFCL was confirmed by a biopsy performed with a seven-month delay, as the tumor had been initially misdiagnosed as a benign lesion. The patient was successfully treated with local radiation therapy. PCFCL is an indolent lymphoma associated with an excellent prognosis. For localized lesions, skin-directed therapies mainly consisting of radiation therapy or complete surgical excision are curative therapeutic approaches, while systemic chemotherapy should be reserved for patients with extensive disease. This case highlights the need to consider PCFCL as an important differential diagnosis in patients presenting with non-resolving erythematous breast skin lesions. A timely biopsy should be obtained to avoid delays in the initiation of appropriate treatment.

A 77-Year-Old Woman With Sjogren Syndrome Experiencing Progressive Dyspnea on Exertion and Nonproductive Cough.

CASE PRESENTATION: A 77-year-old woman was referred to our interstitial lung disease unit. She presented with a history of progressive dyspnea on exertion and nonproductive, persistent cough over the previous year. She was diagnosed with Sjogren syndrome two years ago by a rheumatologist. In the context of Sjogren syndrome, she reported chronic xerostomia and xerophthalmia for the last 5 years. Her history was also notable for the presence of arterial hypertension and hypothyroidism. She denied the presence of shortness of breath, chest pain, arthralgia, muscle weakness, weight loss, night sweats, and fatigue. She reported exposure to house mold. There was no family history of respiratory diseases. The patient never smoked and denied alcohol consumption, illicit drug use, or any occupational exposures.

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.

Lymphoprolipherative skin reactions induced by anti-TNFα: an open question.

Although anti-TNFα agents have revolutionized the treatment of many inflammatory diseases, various concerns have been reported regarding the risks of cancer development, as well as acceleration of the progression of subclinical, preexisting malignancies. In this case series, we investigated the provocative effect of anti-TNFα drugs in the development of cutaneous mycosis fungoides (MF)-like lymphoproliferative reactions. We describe five patients aged between 25-63 diagnosed with autoimmune disorders (psoriatic arthritis - one patient, Crohn's disease - one patient and ankylosing spondylitis - three patients) who received anti-TNFα agents before the development of a cutaneous lymphoproliferative reaction. Histological and immunophenotypical analysis was typical for mycosis fungoides in all of them. Anti-TNFα agents were stopped with regression of the skin rash. A direct effect of anti-TNFα agents in the development of lymphoproliferative reactions (including MF) is suggested and further analyzed. Treatment cessation can be therapeutic.