Key Points Using a sensitive method, the MYD88 (L265P) mutation is detectable in all patients with Waldenström’s macroglobulinemia, therefore representing a hallmark of the disease. MYD88 (L265P) is also found in a substantial proportion of patients with IgM-MGUS.

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The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.

Immunotherapy has become the standard-of-care in many solid tumors. Despite the significant recent achievements in the diagnosis and treatment of cancer, several issues related to patients’ selection for immunotherapy remain unsolved. Multiple lines of evidence suggest that, in this setting, the vision of a single biomarker is somewhat naïve and imprecise, given that immunotherapy does not follow the rules that we have experienced in the past for targeted therapies. On the other hand, additional immune-related biomarkers that are reliable in real-life clinical practice remain to be identified. Recently, the immune-checkpoint blockade has been approved in the US irrespective of the tumor site of origin. Further histology-agnostic approvals, coupled with with tumor-specific companion diagnostics and guidelines, are expected in this field. In addition, immune-related biomarkers can also have a significant prognostic value. In this review, we provide an overview of the role of these biomarkers and their characterization in the management of lung cancer, melanoma, colorectal cancer, gastric cancer, head and neck cancer, renal cell carcinoma, urothelial cancers, and breast cancer.

Halting the vicious cycle within the multiple myeloma ecosystem: blocking JAM-A on bone marrow endothelial cells restores the angiogenic homeostasis and suppresses tumor progression.

Categorization of primary cutaneous B‐cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL‐LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus‐based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL‐LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL‐NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and MUM1, and a “double hit score” upon positivity for BCL2 and MYC. PCDLBCL‐NOS had a clinical presentation more similar to PCFCCL, whereas the histology was more consistent with the picture of a diffuse large B‐cell lymphoma, as predominantly composed of centroblasts but with intermixed a reactive infiltrate of small lymphocytes. Its behavior was intermediate between the other two forms, particularly when considering only cases with a “non‐germinal B‐cell” profile, whereas “germinal center” cases resembled PCFCCL. Our data confirmed the aggressive behavior of PCDLBC‐LT, which often coexpressed MYC and BCL2. The impact of single factors on 5‐year survival was documented, particularly histogenetic profile in PCDLBCL and BCL2 translocation in PCFCCL. Our study confirms that a further group—PCDLBCL‐NOS—exists, which can be recognized through a careful combination of histopathologic criteria coupled with adequate clinical information.

Umbilical endometriosis represents 30–40% of abdominal wall endometriosis and around 0.5–1.0% of all cases of endometriosis. The aim of this systematic review is to revisit the epidemiology, signs, and symptoms and to formulate a pathogenic theory based on literature data. We performed a systematic literature review using the PubMed and Embase databases from 1 January 1950 to 7 February 2021, according to the PRISMA guidelines. The review was registered at PROSPERO (CRD42021239670). Studies were selected if they reported original data on umbilical endometriosis nodule defined at histopathological examination and described as the presence of endometrial glands and/or stromal cells in the connective tissue. A total of 11 studies (10 retrospective and one prospective), and 14 case series were included in the present review. Overall, 232 umbilical endometriosis cases were reported, with the number per study ranging from 1 to 96. Umbilical endometriosis was observed in 76 (20.9%; 95% CI 17.1–25.4) of the women included in studies reporting information on the total number of cases of abdominal wall endometriosis. Umbilical endometriosis was considered a primary form in 68.4% (158/231, 95% CI 62.1–74.1) of cases. A history of endometriosis and previous abdominal surgery were reported in 37.9% (25/66, 95% CI 27.2–49.9) and 31.0% (72/232, 95% CI 25.4–37.3) of cases, respectively. Pain was described in 83% of the women (137/165, 95% CI 76.6–88.0), followed by catamenial symptoms in 83.5% (142/170, 95% CI, 77.2–88.4) and bleeding in 50.9% (89/175, 95% CI 43.5–58.2). In the 148 women followed for a period ranging from three to 92.5 months, seven (4.7%, 95% CI 2.3–9.4) recurrences were observed. The results of this analysis show that umbilical endometriosis represents about 20% of all the abdominal wall endometriotic lesions and that over two thirds of cases are primary umbilical endometriosis forms. Pain and catamenial symptoms are the most common complaints that suggest the diagnosis. Primary umbilical endometriosis may originate from implantation of regurgitated endometrial cells conveyed by the clockwise peritoneal circulation up to the right hemidiaphragm and funneled toward the umbilicus by the falciform and round liver ligaments.

Mucocele (also known as ranula or salivary gland mucous cyst) of the newborn is a lesion present on the intraoral cavity, with the potential to interfere with respiration and feeding. In the present report, a case of mucocele in a 4-month female patient has been described. As conventional surgery can be followed by several complications such as intraoperative bleeding, difficulties in wound healing, and maintenance of sterility during surgery, in the present case, the use of diode laser has been planned. A topic anesthesia with lidocaine gel was performed. A diode laser (810 nm wavelength, continuous wave mode, power output of 3 watt, and 0.4 mm diameter fiber optic) was set for excising the lesion. The tip was directed at an angle of 10 to 15°, moving around the base of the lesion with a circular motion. The procedure was completed in 3 minutes. The patient was visited with a follow-up of 2 weeks and 4 months after excision. The intraoral wound healed without complications, and no signs of infection or mass recurrence were noted. The histopathological examination confirmed the diagnosis of mucocele. On the basis of the results of the present case report, the use of diode laser can be easily performed also in a noncompliant newborn patient for successful excision of mucocele lesions, and checklist of clinical procedures has been described.