Primary Cutaneous Anaplastic Large Cell Lymphoma-A Review of Clinical, Morphological, Immunohistochemical, and Molecular Features.

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.

Mediastinal Lymphoproliferative Disorders.

Lymphoproliferative disorders comprise 50% to 60% of all mediastinal malignancies in both children and adults. Primary mediastinal involvement is rare (∼5%), whereas secondary mediastinal involvement by systemic disease is more common (10% to 25%). Primary mediastinal disease is defined as involvement by a lymphoproliferative disorder of mediastinal lymph nodes, the thymus, and/or extranodal mediastinal organs without evidence of systemic disease at presentation. In this review, the clinical, radiologic, histopathologic, immunohistochemical, and genetic features of some of the most characteristic mediastinal lymphoproliferative disorders are presented. The entities discussed here include: classic Hodgkin lymphoma with emphasis on nodular sclerosis and mixed cellularity types, and non-Hodgkin lymphomas, including primary mediastinal (thymic) large B-cell lymphoma, mediastinal gray zone lymphoma, mediastinal diffuse large B-cell lymphoma, thymic marginal zone lymphoma, mediastinal plasmacytoma, T-lymphoblastic lymphoma, and anaplastic large cell lymphoma. Although not a malignant process, hyaline vascular Castleman disease is also discussed here as this disorder commonly involves the mediastinum. Despite multiple advances in hematopathology in recent decades, the day-to-day diagnosis of these lesions still requires a morphologic approach and a proper selection of immunohistochemical markers. For this reason, it is crucial for general pathologists to be familiar with these entities and their particular clinicoradiologic presentation.

Primary Mediastinal Nodal and Extranodal Non-Hodgkin Lymphomas: Current Concepts, Historical Evolution, and Useful Diagnostic Approach: Part 2.

Primary mediastinal non-Hodgkin lymphomas (PM-NHLs) represent ∼5% of all non-Hodgkin lymphomas (NHLs) and comprise lymphomas of B-cell and T-cell origin. PM-NHLs are defined as involvement of mediastinal lymph nodes, thymus, and/or mediastinal organs (heart, lung, pleura, pericardium) by NHL without evidence of systemic disease at presentation. The clinical scenario is variable and depends on the lymphoma subtype. The radiologic presentation is also variable ranging from a mediastinal mass with or without superior vena cava syndrome, a pleural or a cardiac mass associated with effusion, or as an effusion only. The diagnosis of PM-NHLs can only be established by microscopic evaluation, and therefore, general pathologists should be aware of these tumors and familiar with their diagnostic approach. The most common anterior mediastinal NHLs (90% to 95%) are primary mediastinal (PM) large B-cell lymphoma and T-lymphoblastic lymphoma. Thymic marginal zone lymphoma and mediastinal gray zone lymphoma are very rare. The remainder PM-NHLs involving middle or posterior mediastinum include diffuse large B-cell lymphoma (DLBCL) and rare cases of T-cell lymphoma, including anaplastic large cell lymphoma and breast implant-associated anaplastic large cell lymphoma extending to the anterior mediastinum. Primary pleural and cardiac NHLs are mostly DLBCLs. Other rare subtypes of PM-NHLs include DLBCL associated with chronic inflammation/pyothorax-associated lymphoma, fibrin-associated DLBCL (both Epstein-Barr virus positive), and pleural and/or pericardial primary effusion lymphoma (human herpesvirus-8 positive/Epstein-Barr virus positive). We review the historical aspects, epidemiology, clinicoradiologic features, histopathology, immunohistochemistry, differential diagnosis, and relevant cytogenetic and molecular features of the remaining mediastinal B-cell lymphomas, including primary thymic marginal zone lymphoma of the mucosa-associated lymphoid tissue type, other PM small B-cell lymphomas, PM plasmacytoma, and the most relevant PM T-cell lymphomas.

Primary Mediastinal Nodal and Extranodal Non-Hodgkin Lymphomas: Current Concepts, Historical Evolution, and Useful Diagnostic Approach: Part 1.

Primary mediastinal non-Hodgkin lymphomas (PM-NHLs) represent ~5% of all NHLs and comprise lymphomas of B-cell and T-cell origin. PM-NHLs are defined as involvement of mediastinal lymph nodes, thymus, and/or mediastinal organs (heart, lung, pleura, pericardium) by NHL without evidence of systemic disease at presentation. The clinical scenario is variable and depends on the lymphoma subtype. The radiologic presentation is also variable ranging from a mediastinal mass with or without superior vena cava syndrome, a pleural or a cardiac mass associated with an effusion, or as an effusion only. The diagnosis of PM-NHLs can only be established by microscopic evaluation, and therefore, general pathologists should be aware of these tumors and familiar with their diagnostic approach. The most common anterior mediastinal NHLs (90% to 95%) are primary mediastinal large B-cell lymphoma and T lymphoblastic lymphoma. Thymic marginal zone lymphoma and mediastinal gray zone lymphoma are very rare. The remainder PM-NHLs involving middle or posterior mediastinum include diffuse large B-cell lymphoma (DLBCL) and rare cases of T-cell lymphoma, including anaplastic large cell lymphoma and breast implant-associated anaplastic large cell lymphoma extending to the anterior mediastinum. Primary pleural and cardiac NHLs are mostly DLBCLs. Other rare subtypes of PM-NHLs include DLBCL associated with chronic inflammation/pyothorax-associated lymphoma, fibrin-associated DLBCL (both EBV), and pleural and/or pericardial primary effusion lymphoma (HHV-8/EBV). We review the historical aspects, epidemiology, clinico-radiologic features, histopathology, immunohistochemistry, differential diagnosis, and relevant cytogenetic and molecular features of PM (thymic) LBCL, PM "nonthymic" DLBCL, BCL, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma (mediastinal gray zone lymphoma), DLBCL associated with chronic inflammation (pyothorax-associated lymphoma), fibrin-associated DLBCL, and primary effusion lymphoma. This review represents the first part of 2 manuscripts covering PM-NHLs.

Hematoxylin: Mesoamerica's Gift to Histopathology. Palo de Campeche (Logwood Tree), Pirates' Most Desired Treasure, and Irreplaceable Tissue Stain.

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.

The normal and neoplastic perineurium: a review.

Peripheral nerves consist of 3 layers with differing characteristics: the endoneurium, perineurium, and epineurium. The perineurium represents a continuum with the pia-arachnoid from the central nervous system and extends distally with the sheath of capsular cells of peripheral sensorial organs and propioceptive receptors. It is made of layers of flattened cells surrounded by a basement membrane and collagen fibers, forming concentrically laminated structures around single nerve fascicles. Functionally, the perineurium modulates external stretching forces (that could be potentially harmful for nerve fibers), and along with endoneurial vessels, forms the blood-nerve barrier. Multiple pathologic conditions associated with the perineurium have been described. Perineurial invasion is considered an important prognostic factor in several malignant neoplasms. Perineuriomas are true benign infrequent perineurial cell neoplasms that have been divided in 2 categories: those with intraneural localization and a more common extraneural (soft tissue) group, including sclerosing and reticular variants. Sporadic cases of malignant perineuromas have been reported. Interestingly, neurofibromas and malignant peripheral nerve sheath tumors may also display perineurial cell differentiation. The histologic appearance of perineuriomas may overlap with other soft tissue spindle cell neoplasms. Immunohistochemistry is imperative for the diagnosis, although in certain cases ultrastructural studies may be needed. Typical perineuriomas are positive for epithelial membrane antigen, glucose transporter-1-1, and claudin-1, and negative for S-100 protein and neurofilaments. Perineuriomas have mostly simple karyotypes, with one or few chromosomal rearrangements or numerical changes and it seems that specific cytogenetic aberrations may correlate with perineurioma subtype.

Primary adamantinoma of the rib. Unusual presentation for a bone neoplasm of uncertain origin.

Adamantinomas are rare, low-grade malignant intra-osseous tumors composed of epithelial and mesenchymal elements, which show a marked predilection for the tibia and fibula of young adult male patients. Although cases of adamantinoma located to the axial skeleton have been reported either as recurrent or metastatic disease, only two cases of primary adamantinoma located to the thoracic wall have been previously described. In this study we present the clinical, radiological and histopathological features of a 24-year-old male with a slow growing, solid-cystic, painful mass, located to the right 11th rib, which was morphological and immunohistochemically diagnosed as a primary classic adamantinoma. Radiological studies showed a multiloculated lesion with a solid component. The patient underwent a whole surgical resection of the lesion. Histologically, multiple foci of epithelial cells with basaloid and squamous components were found intermixed within a fibrous stromal tissue. Immunohistochemical analysis demonstrated expression of cytokeratins, EMA, vimentin and other epithelial markers. Primary affection of the rib is an unusual feature of classic adamantinomas.

[Historical development and current concepts on B-cell lymphomas of the marginal extraganglionar site of lymphoid tissue associated with MALT lymphoma. A tribute to Dennis H Wright and Peter G Isaacson]. / Linfoma de céllulas B de la zona marginal extraganglionar del tejido linfoide asociado a mucosas (linfoma MALT). Evolución histórica y conceptos actuales. Un tributo a Dennis H. Wright y Peter G. Isaacson.

Significant advances in the understanding of marginal zone lymphoma since the first description in 1983 by Peter Isaacson and Dennis Wright have been noted. MALT lymphomas are a subgroup of low-grade B-cell lymphomas that arise from extranodal sites, comprising 7-8% of all B-cell lymphomas and displaying distinct clinicopathological characteristics. MALT lymphomas remain localized in the primary site for long periods of time and seldom disseminate unto other organs. These type of lymphomas infrequently arise in native MALT, but instead arise in MALT acquired in the course of chronic inflammatory disorders, such as Sjögren's syndrome and Helicobacter pylori infection. Eradication of H. pylori produces a clinical regression of the lymphoma in about 75% of cases. The histological hallmarks of MALT lymphoma include neoplastic centrocyte-like B cells, cells resembling monocytoid cells and the presence of lymphoepithelial lesions. The gastrointestinal tract, particularly the stomach, include two-thirds of cases; however MALT lymphomas also occur in other organs such as salivary glands, lung, thyroid, ocular adnexa, breast and skin. Genetic studies have identified three chromosomal translocations specifically associated with MALT lymphomas that include: t(1l:18)(q21;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21). Although these translocations involve different genes, they appear to share a common oncogenic pathway involving NFkappaB.

Linfoma de céllulas B de la zona marginal extraganglionar del tejido linfoide asociado a mucosas (linfoma MALT): evolución histórica y conceptos actuales: un tributo a Dennis H. Wright y Peter G. Isaacson / Historical development and current concepts on B-cell lymphomas of the marginal extraganglionar site of lymphoid tissue associated with MALT lymphoma: a tribute to Dennis H Wright and Peter G Isaacson

Se han realizado avances importantes en el entendimiento del linfoma de la zona marginal, (linfoma MALT), desde la primera descripción en 1983 por Peter Isaacson y Dennis Wright. Los linfomas MALT son un subgrupo de neoplasias de bajo grado que representan entre el 7 y el 8 % de todos los linfomas B, que se originan en sitios extraganglionares y presentan características clínico-patológicas propias. Se mantienen localizados por largos periodos de tiempo y sólo ocasionalmente se diseminan a otros órganos. Rara vez se originan de un MALT normal y aparecen en el MALT adquirido en el curso de alteraciones inflamatorias crónicas como en el síndrome de Sjögren o la infección por Helicobacter pylori. La erradicación de H. pylori puede producir regresión clínica del linfoma en un 75 % de los casos. Histológicamente presenta células B neoplásicas centrocitoides, células monocitoides y lesiones linfoepiteliales. El aparato digestivo, particularmente el estómago, está afectado en las dos terceras partes de los casos. Sin embargo, puede presentarse en otros órganos como glándulas salivales, pulmón, tiroides, anexos oculares y piel. Estudios genéticos han identificado tres traslocaciones cromosómicas específicas que son: t(11:18)(q21;q21), t(1;14)(p22;q32), y t(14;18)(q32;q21). A pesar de que estas traslocaciones afectan diferentes genes, comparten una vía oncogénica común que afecta al NFκB.

Significant advances in the understanding of marginal zone lymphoma since the first description in 1983 by Peter Isaacson and Dennis Wright have been noted. MALT lymphomas are a subgroup of low-grade B-cell lymphomas that arise from extranodal sites, comprising 7-8% of all B-cell lymphomas and displaying distinct clinicopathological characteristics. MALT lymphomas remain localized in the primary site for long periods of time and seldom disseminate unto other organs. These type of lymphomas infrequently arise in native MALT, but instead arise in MALT acquired in the course of chronic inflammatory disorders, such as Sjõgren's syndrome and Helicobacter pylori infection. Eradication of H. pylori produces a clinical regression of the lymphoma in about 75% of cases. The histological hallmarks of MALT lymphoma include neoplastic centrocyte-like B cells, cells resembling monocytoid cells and the presence of lymphoepithelial lesions. The gastrointestinal tract, particularly the stomach, include two-thirds of cases; however MALT lymphomas also occur in other organs such as salivary glands, lung, thyroid, ocular adnexa, breast and skin. Genetic studies have identified three chromosomal translocations specifically associated with MALT lymphomas that include: t(1l:18)(q21;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21). Although these translocations involve different genes, they appear to share a common oncogenic pathway involving NFκB.

Pólipos colónicos con cambios tipo-elastofibroma: presentación de dos casos con estudio histoquímico con métodos para fibras elásticas / Presentation of two cases of colonic polyps with elastofibroma-like changes: a study with histochemical methods for elastic fibers

El elastofibroma es una neoplasia benigna de tejidos blandos, que típicamente se presenta en el tejido conectivo localizado en la región inferior de la escápula. La afección visceral es rara y su presentación como pólipos de la mucosa del colon se ha descrito solamente en dos ocasiones. Informamos dos casos de pólipos colónicos que histológicamente presentaron depósitos de un material fibrilar denso en la capa submucosa. Este material resultó ser intensamente positivo para algunas tinciones que resaltan fibras elásticas como el Verhoff, la tinción modificada de Gallego (Reyes- Mota) y el pentacrómico de Movat. Dadas las características histológicas y propiedades histoquímicas de estas lesiones, las cuales se asemejan a las del elastofibroma de tejidos blandos, se estableció el diagnóstico de pólipos colónicos con cambios ‘tipo- elastofibroma’ de la capa submucosa. Estos dos casos representan el tercer y cuarto casos informados en la literatura de esta entidad.

Elastofibroma is a tumor-like lesion of the soft tissues that is usually observed in the connective tissue of the lower portion of the scapulae. Visceral involvement is uncommon and the presentation as colonic polyps has only been described previously twice. Herein, we report two additional cases of colonic polyps with abundant submucosal deposits of a dense elastic fibrillary material which was enhanced with various elastic-fiber staining techniques, like Verhoff, modified Gallego´s stain (Reyes-Mota) and Movat´s pentachromic stain. Histological and histochemical findings of these lesions, which resembled elastofibroma of the soft tissues, established the diagnosis of colonic polyps with ‘elastofibroma-like’ submucosal change. To our knowledge, these are the third and fourth reported cases found in the literature of this uncommon entity.