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Introduction: Our previous studies have demonstrated that tumor-infiltrating lymphocytes (TILs), including normal B cells, T cells, and natural killer (NK) cells, in diffuse large B-cell lymphoma (DLBCL) have a significantly favorable impact on the clinical outcomes of patients treated with standard chemoimmunotherapy. In this study, to gain a full overview of the tumor immune microenvironment (TIME), we assembled a flow cytometry cohort of 102 patients diagnosed with DLBCL at the Duke University Medical Center. Methods: We collected diagnostic flow cytometry data, including the proportion of T cells, abnormal B cells, normal B cells, plasma cells, NK cells, monocytes, and granulocytes in fresh biopsy tissues at clinical presentation, and analyzed the correlations with patient survival and between different cell populations. Results: We found that low T cell percentages in all viable cells and low ratios of T cells to abnormal B cells correlated with significantly poorer survival, whereas higher percentages of normal B cells among total B cells (or high ratios of normal B cells to abnormal B cells) and high percentages of NK cells among all viable cells correlated with significantly better survival in patients with DLBCL. After excluding a small number of patientswith low T cell percentages, the normal B cell percentage among all B cells, but not T cell percentage among all cells, continued to show a remarkable prognostic effect. Data showed significant positive correlations between T cells and normal B cells, and between granulocytes and monocytes. Furthermore, we constructed a prognostic model based on clinical and flow cytometry factors, which divided the DLBCL cohort into two equal groups with remarkable differences in patient survival and treatment response. Summary: TILs, including normal B cells, T cells, and NK cells, are associated with favorable clinical outcomes in DLBCL, and flow cytometry capable of quantifying the TIME may have additional clinical utility for prognostication. [ABSTRACT FROM AUTHOR]

Pulmonary lymphomas are rare. With the current less invasive approaches used to obtain material for diagnosis, the diagnosis of pulmonary lymphoma is now frequently established in a small biopsy rather than in a resection. Therefore, the diagnosis has become more challenging and requires correlation with the clinico-radiologic presentation and with ancillary studies (immunohistochemistry, flow cytometry, cytogenetics, and/or molecular analysis). Due to the rarity of pulmonary lymphomas, clinical suspicion of a lymphomatous process is low at initial presentation, and material may be only submitted for histopathology. For this reason, herein, we provide recommendations to arrive at the correct diagnosis of the most common lung B-cell lymphomas (marginal zone lymphoma of mucosa-associated lymphoid tissue, diffuse large B-cell lymphoma, intravascular large B-cell lymphoma, lymphomatoid granulomatosis) in the setting of small biopsies, utilizing only immunohistochemistry. The differential diagnosis varies according to the lymphoma subtype and includes reactive conditions, solid tumors, and other hematolymphoid malignancies. Although morphology and immunohistochemistry may be sufficient to establish a diagnosis, in some cases, the best recommendation is to obtain additional tissue via a VATS biopsy/wedge resection with material submitted for flow cytometry, cytogenetics, and/or molecular studies to be able to properly classify a pulmonary lymphoid process. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides. Although it usually presents as a localized nodule or papule (>2 cm), multifocal lesions may occur in some cases. Patients have an overall good prognosis either in localized or multifocal disease. Microscopically, this neoplasm consists of a dermal infiltrate of medium to large anaplastic cells that may extend to the subcutis. By immunohistochemistry, this tumor is strongly positive for CD30. Primary cutaneous ALCL can mimic several reactive skin conditions as well as other lymphoproliferative disorders, such as lymphomatoid papulosis, more aggressive primary cutaneous lymphomas, or systemic lymphomas involving the skin. Therefore, it is crucial to know the clinical presentation before establishing a diagnosis of primary cutaneous ALCL. Here, we review the clinical and histopathological features of primary cutaneous ALCL as well as its differential diagnosis and most common genetic alterations known to date. Primary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides and belongs to the spectrum of cutaneous CD30+ T-cell lymphoproliferative disorders. Although primary cutaneous ALCL usually presents as a localized nodule or papule with or without ulceration, multifocal lesions may occur in up to 20% of cases. Histologically, primary cutaneous ALCL consists of a diffuse dermal infiltrate of medium to large anaplastic/pleomorphic cells with abundant amphophilic-to-eosinophilic cytoplasm, horseshoe-shaped nuclei, strong and diffuse expression of CD30, and with focal or no epidermotropism. The neoplastic infiltrate may show angiocentric distribution and may extend to the subcutis. Patients with localized or multifocal disease have a similar prognosis with a 10-year overall survival rate of 90%. Approximately 30% of primary cutaneous ALCLs harbor a DUSP22 (6p25.3) gene rearrangement that results in decreased expression of this dual-specific phosphatase, decreased STAT3 activation, and decreased activity of immune and autoimmune-mediated mechanisms regulated by T-cells. [ABSTRACT FROM AUTHOR]

The 2021 "World Health Organization (WHO) Classification of Thoracic Tumours" classifies epithelial tumors of the thymus (thymomas) based on cytomorphology. Thymomas with benign cytomorphology are classified as type A, AB, B1, B2, and B3, while those with malignant cytomorphology are classified as thymic carcinoma. Although all thymomas have malignant potential, extra-thoracic metastasis of thymomas is exceedingly rare and the exact incidence is not known. Literature review demonstrated 39 cases of thymoma with extra-thoracic metastases reported since the publication of the 1999 WHO Classification of Thoracic Tumours. Nine of these cases presented with metastasis to the liver in the setting of concurrent metastasis to other organs, while only three cases metastasized solely to the liver. We herein report a well-documented case of type B1 thymoma with relatively limited stage (IIb) with an isolated, single liver metastasis occurring seven years after primary resection in a patient with concomitant myasthenia gravis. The following report includes a review of the literature, a discussion of thymoma classification and its relevance to prognosis, and an overview of other extra-thoracic metastatic thymoma cases. [ABSTRACT FROM AUTHOR]

Nuclear protein in testis (NUT) carcinoma is a rare, highly aggressive, poorly differentiated carcinoma occurring mostly in adolescents and young adults. This tumor usually arises from the midline structures of the thorax, head, and neck, and exhibits variable degrees of squamous differentiation. NUT carcinoma is defined by the presence of a NUTM1 (15q14) rearrangement with multiple other genes. In about 70-80% of the cases, NUTM1 is involved in a balanced translocation with the BRD4 gene (19p13.12), leading to a BRD4-NUTM1 fusion oncogene. Other variant rearrangements include BRD3-NUTM1 fusion (~15-20%) and NSD3-NUTM1 fusion (~6%), among others. The diagnosis of NUT carcinoma requires the detection of nuclear expression of the NUT protein by immunohistochemistry. Additional methods for diagnosis include the detection of a NUTM1 rearrangement by fluorescence in situ hybridization or by reverse transcriptase PCR. NUT carcinoma is usually underrecognized due to its rarity and lack of characteristic histological features. Therefore, the goal of this review is to provide relevant recent information regarding the clinicopathologic features of NUT carcinoma, the role of the multiple NUTM1 gene rearrangements in carcinogenesis, and the impact of understanding these underlying molecular mechanisms that may result in the development of possible novel targeted therapies. [ABSTRACT FROM AUTHOR]

A synchronous diagnosis of a plasma cell neoplasm (PCN) and a non-plasma cell hematologic malignancy is very rare. We report what we believe is the first instance of a synchronous PCN and B lymphoblastic leukemia/lymphoma (B-ALL) diagnosed at initial presentation. The patient underwent laboratory evaluation for an underlying plasma cell neoplasm, including immunology studies, bone marrow biopsy, and flow cytometry immunophenotyping. Serum lambda free light chain and serum IgG were elevated, with an IgG lambda M-protein identified by serum protein electrophoresis and immunofixation. The clinical working diagnosis was plasma cell myeloma. Bone marrow biopsy was positive for a composite PCN and B-ALL. The patient received treatment with VDT-PACE chemotherapy followed by autologous stem cell transplant and maintenance therapy with bortezomib/daratumumab and is in complete remission for both diseases 3.5 years after diagnosis. This case not only adds to the known repertoire of hematologic neoplasms that can occur in association to a PCN, but also demonstrates that patients presenting with this rare combination of hematopoietic neoplasms can be effectively treated simultaneously with excellent responses. Additional research is warranted to understand the pathophysiology, to identify potential prognostic factors, and to develop specific therapeutic plans for these patients. [ABSTRACT FROM AUTHOR]

Hematoxylin is a basic dye derived from the heartwood of Palo de Campeche (Haematoxylum campechianum), the logwood tree native to Mexico and Central America. Haematoxylum means "bloodwood" in reference to its dark-red heartwood and campechianum refers to its site of origin, the coastal city of Campeche on the Yucatan Peninsula, Mexico. Hematoxylin is colorless but it turns into the color dye hematein after oxidation (ripening). The dyeing property of logwood was well-known to the natives of the Yucatan Peninsula before the arrival of the Spaniards who brought it to Europe shortly after the discovery of the Americas. An important trade soon developed related to growing and preparing hematoxylin for dyeing fabrics. Pirates discovered that one shipload of logwood was equivalent to a year's value from any other cargo, and by 1563, more than 400 pirate vessels wandered the Atlantic Ocean and attacked Spanish galleons transporting gold, silver, and logwood from the Americas to Europe. Hematoxylin and eosin is a staining method that dates back to the late 19th century. In 1865 and 1891, Böhmer and Meyer, respectively, first used hematoxylin in combination with a mordant (alum). Later, with the use of anilines by Ehrlich, the repertoire of stains expanded rapidly resulting in the microscopic descriptions of multiple diseases that were defined by their stainable features. Today hematoxylin, along with eosin, remains the most popular stain in histology. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This study reveals the importance of recognizing uncommon histologic variants in diffuse large B‐cell lymphoma, such as the signet‐ring cell variant, which may result in an erroneous or delayed diagnosis with potential impact in patient treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: ALK- anaplastic large cell lymphoma (ALK- ALCL) is a rare subtype of CD30+ large T-cell lymphoma that typically affects older adults and has a poor prognosis. Recognition of its histopathologic spectrum, subtypes, and of other tumors that can resemble ALK- ALCL is crucial to avoid making a wrong diagnosis that could result in inappropriate treatment for a patient. In recent years, several important studies have identified recurrent molecular alterations that have shed light on the pathogenesis of this lymphoma. However, on the other hand, putting all this vast information together into a concise form has become challenging. In this review, we present not only a more detailed view of the histopathologic findings of ALK- ALCL but also, we attempt to provide a more simplified perspective of the relevant genetic and molecular alterations of this type of lymphoma, that in our opinion, is not available to date. Anaplastic large cell lymphoma (ALCL) is a subtype of CD30+ large T-cell lymphoma (TCL) that comprises ~2% of all adult non-Hodgkin lymphomas. Based on the presence/absence of the rearrangement and expression of anaplastic lymphoma kinase (ALK), ALCL is divided into ALK+ and ALK-, and both differ clinically and prognostically. This review focuses on the historical points, clinical features, histopathology, differential diagnosis, and relevant cytogenetic and molecular alterations of ALK- ALCL and its subtypes: systemic, primary cutaneous (pc-ALCL), and breast implant-associated (BIA-ALCL). Recent studies have identified recurrent genetic alterations in this TCL. In systemic ALK- ALCL, rearrangements in DUSP22 and TP63 are detected in 30% and 8% of cases, respectively, while the remaining cases are negative for these rearrangements. A similar distribution of these rearrangements is seen in pc-ALCL, whereas none have been detected in BIA-ALCL. Additionally, systemic ALK- ALCL—apart from DUSP22-rearranged cases—harbors JAK1 and/or STAT3 mutations that result in the activation of the JAK/STAT signaling pathway. The JAK1/3 and STAT3 mutations have also been identified in BIA-ALCL but not in pc-ALCL. Although the pathogenesis of these alterations is not fully understood, most of them have prognostic value and open the door to the use of potential targeted therapies for this subtype of TCL. [ABSTRACT FROM AUTHOR]