Mast Cell Leukemia: An Update with a Practical Review.

Mast cell leukemia (MCL) is the leukemic form of SM with at least 20% mostly immature mast cells on bone marrow aspirate. MCL may develop de novo, in the absence of a prior SM, or it may represent a progression from a previous SM. MCL may be sub-divided into the more frequent, aggressive acute form with signs of organ damage (C-findings) and the chronic form lacking C-findings and presenting a more stable course, although over time, progression to acute MCL is common. The 2022 WHO subtype of MCL with an associated hematological neoplasm was renamed MCL with an associated myeloid neoplasm in the 2022 International Consensus Classification (ICC). The relevance of the distinction between the leukemic and aleukemic forms based on the percentage of circulating mast cells is a matter of debate. The current knowledge on MCL is restricted mainly to single reports or case series with a limited number of larger studies. Our aim is to provide a comprehensive overview of this rare disease in terms of clinical manifestations, morphology, phenotype, molecular characteristics, differential diagnosis, outcome and treatment. A general overview on mastocytosis is also included.

How to Treat Algodystrophy and Rheumatic Comorbidity in Myelofibrosis: Three Case Reports.

Algodystrophy or complex regional pain syndrome is a chronic pain condition characterized by hyperalgesia and allodynia. Patients with algodystrophy present an amplified and persistent activation of the innate immune system, with subsequent proliferation of keratinocytes and release of proinflammatory cytokines including interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α). Chronic inflammation and increased levels of cytokines are observed also in Ph-negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Chronic myeloid neoplasms are characterized by overproduction of one or more mature non-lymphoid cell lineages, with erythrocytosis, thrombocytosis, and/or myeloproliferation. Three case reports described our experience in the treatment of algodystrophy and rheumatic conditions in patients with myelofibrosis; a literature search was also performed. The first patient was a 58-year-old woman who suffered from chronic myeloproliferative neoplasm in myelofibrotic evolution, under treatment with ruxolitinib and pre-treated with hydroxyurea; she reported inflammatory pain, and swelling of the tibiotarsal joints bilaterally. She was treated with neridronate 2 mg/kg for four days and methotrexate 15 mg per os per week, achieving a clinical benefit. The second patient was a 63-year-old woman diagnosed with polycythemia vera evolving to myelofibrosis. She experienced pain and swelling of the left tibiotarsal joint and difficulty walking. A therapy with low-dose steroid per os and intramuscular clodronate was administered for four months, followed by methotrexate at 15 mg per week. After two months, tenosynovitis significantly improved, as supported by the evidence of improved bone edema of the left tibiotarsal joint revealed in the magnetic resonance imaging, and pain symptoms were clinically ameliorated. The third patient was a 70-year-old male patient affected by essential thrombocythemia with myelofibrotic evolution and a paraneoplastic polymyalgia rheumatica treated with steroids and currently in remission. The patient received ruxolitinib for about two years; after the first year of treatment, he experienced pain and swelling of the right tibiotarsal joint with difficulty in walking, with a consequent diagnosis of edema and tenosynovitis, as per algodystrophy. After consulting a rheumatologist, the patient received therapy with neridronate intramuscularly with clinical benefit. As overlapping interactions and clinical manifestations between hematologic neoplasms and rheumatologic diseases exist, new clinical manifestations, such as algodystrophy, may emerge during myelofibrosis and need to be monitored in the long term by a multidisciplinary team.

Laugier-Hunziker syndrome: a case and dermoscopic features.

Laugier-Hunziker syndrome (LHS) is a sporadic, acquired, and infrequent condition characterized by the onset of brown macules on the lips, the oral mucosa, and the acral glabrous skin (mainly fingers and toes) in middle-aged patients. In several cases melanonychia of fingernails and toenails coexists. No other systemic involvement is observed. A case of LHS in a 50-year-old woman is described, with particular attention to dermoscopic features. No dermoscopic specific findings of mucosal/cutaneous maculae have been to date described in the literature. Accumulation of dermoscopic observations of pigmented lesions in LHS is needed and if found to be distinct, it may contribute to a more accurate diagnosis in the future.

Alterations of MEN1 and E-cadherin/ß-catenin complex in sporadic pulmonary carcinoids.

Pulmonary carcinoids, distinct in typical and atypical, represent 2-5% of all primary lung tumors. The aim of this study was to investigate the molecular alterations correlated with the development of this form of neoplasms. A collection of 38 paraffin-embedded apparently sporadic carcinoids was investigated, through a combined study, for protein expression/localization of menin, p53, ß-catenin and E-cadherin and for mutational analysis of the MEN1, TP53 and CTNNB1 genes. Menin was expressed in 71% of cases, with a prevalent cytoplasmic (c) localization, ß-catenin was expressed in 68.4% of cases, of which 36.8% with a membranous (m) and 31.6% with a cytoplasmic localization. Membranous E-cadherin immunoreactivity was detected in 84.2% cases, nuclear p53 expression in 5.3% of cases. Positive correlation was found between c-menin and c-ß-catenin expression (rho=0.439, P=0.008). In addition, m-ß-catenin showed a positive correlation with both c-ß-catenin and E-cadherin expression (rho=0.380, P=0.022 and rho=0.360, P=0.040, respectively). With regard to the E-cadherin/ß-catenin complex, we found also a significant positive correlation between c-menin and 'disarrayed' ß-catenin expression (rho=0.481, P=0.007). MEN1 gene variants were characterized in 34% of cases. c-menin was more highly expressed in tumors with MEN1 variants, compared to tumors without MEN1 variants (P=0.023). Three nucleotide variants of TP53 were also detected. This study confirms the involvement of the MEN1 gene in the development of sporadic pulmonary carcinoids, demonstrates the accumulation of menin in the cytoplasm, and indicates that the disarrayed pattern of the complex significantly correlates with c-menin accumulation.

Leishmania life cycle images in the cutaneous cytologic smear of an immunocompetent patient.

Cutaneous leishmania life cycle images on cytology smears are very rare. We report herein a gallery of cytologic images from a case of sporadic cutaneous leishmaniasis in a 61 year old man presenting with ulcerative skin lesion.

The prostate-associated lymphoid tissue (PALT) is linked to the expression of homing chemokines CXCL13 and CCL21.

BACKGROUND: The genitourinary tract is regarded as part of the mucosal immune system. However, the structural and functional aspects of the human prostate-associated lymphoid tissue (PALT) have never been extensively explored. METHODS: This article describes our investigation of this issue by means of immunohistological, confocal, and ultrastructural examination of the normal human prostate. RESULTS: PALT consists of two main components: (1) intraepithelial leukocytes, namely CD3(+)T cells with prevalent CD8(+) and CD45RA(-)CD45RO(+) phenotype, sometimes CD69(+), followed by CD94(+)NK, CD11c(+)DCs, some expressing CD86, DC-SIGN(+)DCs and a few B lymphocytes; (2) lymphoid aggregates, frequently below the epithelia, arranged in B cell follicles, endowed with a central ICAM-1(+)VCAM-1(+)CD21(+)FDCs network expressing BLC/CXCL13, and parafollicular T cell areas crossed by PNAd(+)HEV-like vessels showing SLC/CCL21 expression. Parafollicular areas were formed of prevalent CD4(+)T lymphocytes, both CD45RA(-) and CD45RO(+), and intermingled with CD11c(+)DCs. Germinal-center-containing follicles are few and their parafollicular areas are scantily infiltrated by Foxp3(+)CD69(-) highly suppressive regulatory T cells. Most lymphoid follicles lack a distinct germinal center and their parafollicular area harbor numerous Foxp3(+)CD69(-) cells. CONCLUSIONS: Comparison with the tonsils shows that PALT displays immunomorphological features required for the onset of cellular and humoral immune responses, while its T regulatory cells appear to function as suppressor-regulators of T and B cell responses.