Breast implant-associated anaplastic large cell lymphoma: clinical follow-up and analysis of sequential pathologic specimens of untreated patients shows persistent or progressive disease.

Breast implant-associated anaplastic large cell lymphoma (ALCL) is a distinctive type of T-cell lymphoma that arises around textured-surface breast implants. In a subset of patients, this disease can involve surrounding tissues, spread to regional lymph nodes, and rarely metastasize to distant sites. The aim of this study was to assess sequential pathologic specimens from patients with breast implant-associated ALCL to better understand the natural history of early-stage disease. To achieve this goal, we searched our files for patients who had breast implant-associated ALCL and who had undergone earlier surgical intervention with assessment of biopsy or cytologic specimens. We then focused on the patient subset in whom a definitive diagnosis was not established, and patients did not receive current standard-of-care therapy at that time. We identified a study group of ten patients with breast implant-associated ALCL in whom pathologic specimens were collected 0.5 to 4 years before a definitive diagnosis was established. A comparison of these serial biopsy specimens showed persistent disease without change in pathologic stage in three patients, progression in five patients, and persistence versus progression in two patients. Eventually, six patients underwent implant removal with complete capsulectomy and four underwent partial capsulectomy. Seven patients also received chemotherapy because of invasive disease, three of whom also received radiation therapy, two brentuximab vedotin after chemotherapy failure, and one allogeneic stem cell transplant. Eight patients achieved complete remission and two had partial remission after definitive therapy. At time of last follow-up, six patients were alive without disease, one had evidence of disease, one died of disease, and two patients died of unrelated cancers. In summary, this analysis of sequential specimens from patients with breast implant-associated ALCL suggests these neoplasms persist or progress over time if not treated with standard-of-care therapy.

Management of Residual Disease After First-line Chemotherapy in a Patient With a Nonseminomatous Germ Cell Tumor.

The case An 18-year-old male presented with a one-month history of a nonpainful right testicular enlargement. He had no family history of neoplasia, nor any relevant past medical history. The physical examination was only remarkable for an enlarged right testicle. A testicular ultrasound revealed a 2.5-cm tumor, and serum tumor markers revealed an elevated ß-human chorionic gonadotropin (ß-HCG), 22 mUI/L (normal, < 0.06 mUI/L); elevated alpha-fetoprotein (AFP), 329 ng/mL (normal, 0-9 ng/mL); and normal lactate dehydrogenase (LDH), 135 /L (normal, 179 U/L). A right radical inguinal orchiectomy was performed. Pathological examination revealed a 2.4 cm by 2 cm embryonal carcinoma with tumor invasion into the tunica albuginea. Postsurgical tumor markers obtained 3 weeks after orchiectomy were ß-hCG, 100.5 mUI/L (normal, < 0.06 mUI/L); AFP, 1075 ng/mL (normal, 0-9 ng/mL); and LDH, 180 U/L (normal, 179 U/L). A chest, abdomen, and pelvis CT scan showed a 2.7-cm retroperitoneal lymph node enlargement, without visceral metastasis. Given the presence of node-positive disease with S2 serum markers, the diagnosis of a stage IIIB intermediate risk nonseminomatous germ cell tumor (NSGCT) was determined, and the patient underwent sperm banking. The patient was started on chemotherapy with 4 cycles of BEP (bleomycin, etoposide, and cisplatin), with a favorable tumor marker decline according to the Gustave-Roussy nomogram. After completion of the fourth chemotherapy cycle, serum tumor markers were negative, and 8 weeks after chemotherapy, the follow-up CT showed a 1.6-cm residual retroperitoneal lymph node conglomerate.

Carl von Rokitansky, the Linné of pathological anatomy.

Carl von Rokitansky was one of the most important figures in pathological anatomy, and was largely responsible for the resurgence of Vienna as the great medical center of the world in the mid-19th century. He was born in current Hradec Králové, studied medicine in Prague and Vienna and was graduated in 1828. He was greatly influenced by the anatomy, embryology and pathology studies of Andral, Lobstein and Meckel. At the Vienna School, he was Johann Wagner pathological anatomy assistant and became a pathology professor, where he remained until four years before his death. Rokitansky emphasized the importance of correlating patient symptoms with postmortem changes. It is possible that he had access to between 1,500 and 1,800 cadavers annually to be able to perform 30,000 necropsies; in addition, he reviewed several thousand more autopsies. In Handbuch der pathologischen Anatomie, published between 1842 and 1846, he made numerous descriptions: lobar and lobular pneumonia, endocarditis, diseases of the arteries, cysts in several viscera, various neoplasms and acute yellow atrophy of the liver. With his brilliant work on gross pathology, Rokitansky established the nosological classification of diseases, for which Virchow named him "the Lineé of pathological anatomy".Carl von Rokitansky fue una de las figuras más importantes en la anatomía patológica y el responsable, en parte, del renacimiento de Viena como centro de la medicina a mediados del siglo XIX. Nació en la actual Hradec Králové, estudió medicina en Praga y Viena y se graduó en 1828. Tuvo gran influencia de los estudios de anatomía, embriología y patología de Andral, Lobstein y Meckel. En la escuela de Viena fue asistente de anatomía patológica de Johann Wagner y se convirtió en profesor de anatomía patológica, donde permaneció hasta cuatro años antes de su muerte. Rokitansky hizo énfasis en correlacionar la sintomatología del enfermo con los cambios post mortem. Es posible que haya tenido acceso a entre 1500 y 1800 cadáveres al año para que pudiera realizar 30 000 necropsias; además, revisó varios miles más de autopsias. En Handbuch der Pathologischen Anatomie, publicado entre 1842 y 1846, realizó numerosas descripciones: de la neumonía lobular y lobular, endocarditis, enfermedades de las arterias, quistes en varias vísceras, diversas neoplasias y de la atrofia aguda amarilla del hígado. Con su brillante labor de patología macroscópica, Rokitansky estableció la clasificación nosológica de las enfermedades, por lo cual Virchow lo llamó "el Linneo de la anatomía patológica".

Discriminant analysis and machine learning approach for evaluating and improving the performance of immunohistochemical algorithms for COO classification of DLBCL.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) and non-germinal center-like (non-GCB) cell-of-origin groups, entities driven by different oncogenic pathways with different clinical outcomes. DLBCL classification by immunohistochemistry (IHC)-based decision tree algorithms is a simpler reported technique than gene expression profiling (GEP). There is a significant discrepancy between IHC-decision tree algorithms when they are compared to GEP. METHODS: To address these inconsistencies, we applied the machine learning approach considering the same combinations of antibodies as in IHC-decision tree algorithms. Immunohistochemistry data from a public DLBCL database was used to perform comparisons among IHC-decision tree algorithms, and the machine learning structures based on Bayesian, Bayesian simple, Naïve Bayesian, artificial neural networks, and support vector machine to show the best diagnostic model. We implemented the linear discriminant analysis over the complete database, detecting a higher influence of BCL6 antibody for GCB classification and MUM1 for non-GCB classification. RESULTS: The classifier with the highest metrics was the four antibody-based Perfecto-Villela (PV) algorithm with 0.94 accuracy, 0.93 specificity, and 0.95 sensitivity, with a perfect agreement with GEP (κ = 0.88, P < 0.001). After training, a sample of 49 Mexican-mestizo DLBCL patient data was classified by COO for the first time in a testing trial. CONCLUSIONS: Harnessing all the available immunohistochemical data without reliance on the order of examination or cut-off value, we conclude that our PV machine learning algorithm outperforms Hans and other IHC-decision tree algorithms currently in use and represents an affordable and time-saving alternative for DLBCL cell-of-origin identification.

Approach to dermal-based lymphoid infiltrates and proliferations.

The histopathological diagnosis of dermal-based lymphoid infiltrates and proliferations is often challenging due to the vast list of biologically diverse entities that archetypally or occasionally center in the mid-dermis, especially because significant overlap exists in their clinical, histopathologic, and immunophenotypic features. The differential diagnosis includes reactive infiltrates in common and rare inflammatory dermatoses, benign conditions that may mimic lymphoid neoplasms (pseudolymphomas), and true clonal proliferations arising either primarily in the skin or rarely in extracutaneous tissues with secondary cutaneous dissemination. While numerous histopathological and immunophenotypic features have been reported to support a definitive diagnosis, no single ancillary test is sufficient for their distinction. Therefore, in this review we advocate a stepped histopathological approach for dermalbased lymphoid infiltrations, employing as key elements the general lymphocytic composition (relative B- versus T-cell ratio), coupled with the predominant cytomorphology (cell size) present. Following this strategy, the relative incidence of cutaneous involvement by each disease should always be considered, as well as the notion that a definitive diagnosis must be founded on a multiparameter approach integrating all clinical, histopathologic, immunophenotypic, and-in selected cases-molecular features.

Myopericytoma in an unusual location.

Myopericytoma is a soft-tissue tumor of perivascular cells (pericytes). It is slow-growing, usually asymptomatic, and generally benign, although a malignant variant has been described. The etiology is unknown, but it has been associated with local trauma. The most common location is on the distal extremities. Histologically, it is characterized by a well-circumscribed, non-encapsulated proliferation of spindle shaped cells similar to myofibroblasts with oval nuclei and eosinophilic cytoplasm, arranged in perivascular concentric rings. There are few mitoses and no necrosis is reported. The immunohistochemical analysis is positive for smooth muscle actin and negative or weakly positive for desmin. A low Ki-67 proliferation index is typical. Treatment is surgical excision with free margins. Recurrences after adequate excision are uncommon. We describe a 48-year-old woman with a myopericytoma in an unusual location (next to the inner corner of her left eye) who was treated with surgical excision; there has been no recurrence after 5 years of follow up.

EMMPRIN (CD147) is induced by C/EBPß and is differentially expressed in ALK+ and ALK- anaplastic large-cell lymphoma.

Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL) is characterized by expression of oncogenic ALK fusion proteins due to the translocation t(2;5)(p23;q35) or variants. Although genotypically a T-cell lymphoma, ALK+ ALCL cells frequently show loss of T-cell-specific surface antigens and expression of monocytic markers. C/EBPß, a transcription factor constitutively overexpressed in ALK+ ALCL cells, has been shown to play an important role in the activation and differentiation of macrophages and is furthermore capable of transdifferentiating B-cell and T-cell progenitors to macrophages in vitro. To analyze the role of C/EBPß for the unusual phenotype of ALK+ ALCL cells, C/EBPß was knocked down by RNA interference in two ALK+ ALCL cell lines, and surface antigen expression profiles of these cell lines were generated using a Human Cell Surface Marker Screening Panel (BD Biosciences). Interesting candidate antigens were further analyzed by immunohistochemistry in primary ALCL ALK+ and ALK- cases. Antigen expression profiling revealed marked changes in the expression of the activation markers CD25, CD30, CD98, CD147, and CD227 after C/EBPß knockdown. Immunohistochemical analysis confirmed a strong, membranous CD147 (EMMPRIN) expression in ALK+ ALCL cases. In contrast, ALK- ALCL cases showed a weaker CD147 expression. CD274 or PD-L1, an immune inhibitory receptor ligand, was downregulated after C/EBPß knockdown. PD-L1 also showed stronger expression in ALK+ ALCL compared with ALK- ALCL, suggesting an additional role of C/EBPß in ALK+ ALCL in generating an immunosuppressive environment. Finally, no expression changes of T-cell or monocytic markers were detected. In conclusion, surface antigen expression profiling demonstrates that C/EBPß plays a critical role in the activation state of ALK+ ALCL cells and reveals CD147 and PD-L1 as important downstream targets. The multiple roles of CD147 in migration, adhesion, and invasion, as well as T-cell activation and proliferation suggest its involvement in the pathogenesis of ALCL.

Castleman disease. Histopathological and immunohistochemical analysis of 39 cases. / Enfermedad de Castleman. Análisis histopatológico e inmunohistoquímico de treinta y nueve casos.

Introduction: Castleman disease (CD) is a rare lymphoproliferative that comprises two distinct clinical subtypes (unicentric and multicentric) and has two basic histopathology patterns that are hyaline-vascular (HV) and plasma-cell (PC) type. Some cases of multicentric PC disease are associated with HHV-8 infection. Objective: To present the histopathologic and immunohistochemical characteristics of 39 cases of CD. Methods: A review of cases with the diagnosis CD from the files of the Department of Pathology of the ABC Medical Centre in Mexico City was performed. Thirty-nine cases of CD were identified, and a detailed paraffin immunophenotypic study of 9 of them was completed using desmin, cytokeratin OSCAR (CO) and Epidermal growth factor receptor (EGFR), to evaluate the dendritic cell population. Results and Conclusions: Of the 39 cases of CD, 24 were HV and 15 CP. All HV cases were unicentric and only one case of CP was multicentric. The most frequent localization in both subtypes was in lymph nodes; 21/24 cases in HV and 15 cases of CP. All cases were immunostained with CD20 that was expressed in the germinal centers (CGs), CD3 in the paracortical zone, and CD21 in follicular dendritic cells (CDF) within CGs, with expansion towards the area of the hyperplastic mantle zone (only in the HV variant). One case of CD CP was positive for HHV-8. Of the nine cases (6 HV and 3 PC cases) that were detailed with IHC, we found EGFR expression in FDC in all but one of the 9 cases studied and desmin was positive in fibroblastic reticulum cells (FRC) in all, but one of the cases of CD. CO was positive FRC in 3 of 6 cases of HV type and all (3) of the PC type. Clinical, histopathological and HIV and HHV-8 status markers, allow for the classification of CD into groups with markedly different outcomes and disease associations.

[Utility of bone marrow biopsy in the diagnosis of myeloproliferative neoplasm]. / Utilidad de la biopsia de Médula Ósea (MO) en el diagnóstico de las Neoplasias Mieloproliferativas (NMP).

A diagnostic approach of myeloproliferative neoplasms, according to the 2008 WHO classification system for hematological malignancies, has to consider clinical, molecular, and cytogenetic information as well as bone marrow histology. A diagnosis of chronic myeloid leukemia requires the presence of BCR-ABL-1, and the Philadelphia chromosome-negative (Ph-1-negative) myeloproliferative neoplasms constitute three main subtypes, including primary myelofibrosis, polycythemia rubra vera, and essential thrombocythemia. These three Ph-1-negative myeloproliferative neoplasms share many pathogenic characteristic such as JAK2 mutations; however, they differ in prognosis, progression to myelofibrosis, and risk of leukemic transformation. There are currently various major points of interest in bone marrow examination in myeloproliferative neoplasms. One is the morphology of megakaryocytes, which are the hallmark of Ph-1-negative myeloproliferative neoplasms and play a crucial role in separating the different subtypes of myeloproliferative neoplasms. Another is reticulin fibrosis or collagen fibrosis, which may only be detected on a bone marrow biopsy specimen by reticulin and trichrome stains, respectively, and immunohistochemistry and certain molecular techniques may be applied in bone marrow biopsies as supporting evidence of certain features of myeloproliferative neoplasms.

[The professor and the seamstress: an episode in the life of Jacob Henle]. / El profesor y la costurera: un episodio de la vida de Jacob Henle.

Jacob Henle was a great German anatomist and one of the most important histologists of all times. One of the most commonly used eponymous terms in renal histology is the loop of Henle, but many other anatomical and pathological findings are associated with his name. During his stay in Zurich he fell in love with Elise Egolff who worked as a maid and seamstress in the house of one of his friends. No one could ever imagine how the wide social chasm that separated the servant-girl and the professor could be bridged. Henle arranged for his sister Marie to educate Elise and give her social polish. In a short time Elise was transformed into a lady of the world. A year and a half later Jacob and Elise were married. This episode inspired the novelist Auerbach to write the novel "The Professor's Wife", and the play "Pygmalion" by George B Shaw.

[Sclerosing acral skin perineurioma: clinicopathologic study of ten cases (eight classical and two with xanthomatous changes)]. / Perineuroma esclerosante de piel acral: estudio histopatológico de diez casos (ocho clásicos y dos con cambios xantomatosos).

INTRODUCTION: Perineurioma is an infrequent and benign cutaneous neoplasm characterized by proliferation of perineurial cells. It is classified into two main types: intraneural and the extraneural or soft tissue perineurioma, in which the sclerosing variant is included. Sclerosing perineurioma is more frequently found on acral skin. Clinically, they are well-circumscribed,skin colored, nodular tumors. OBJECTIVE: Describe and communicate clinicopathologic findings from a case series of sclerosing acral perineurioma. MATERIAL AND METHODS: This is a clinical, morphological and immunohistologic case study of eight patients with the diagnosis of sclerosing perineurioma. RESULTS: It included five men and five women, with ages ranging between nine and 66 years. All of them had lesion on acral skin. At microscopy study, the lesions showed a proliferation of epithelioid and spindle-shaped perineurial cells, arranged in small aggregates and short fascicles between thickened collagen bundles. Immunohistochemistry studies revealed that the proliferating cells expressed EMA, Claudin-1 and Glut-1, and were negative for S-100 protein. CONCLUSIONS: It is important to report these infrequent skin tumors, so they can be taken into account in the differential diagnoses of acral lesions.

[Pseudolymphomatous folliculitis: a study of the clinicopathologic and immunohistochemical characteristics of 19 cases and their diagnostic differential]. / Foliculitis pseudolinfomatosa. Estudio clinicopatológico e inmunohistoquímico de 19 casos y su diagnóstico diferencial.

INTRODUCTION: Pseudolymphomatous folliculitis (PLF) is a rare benign cutaneous lymphoid hyperplasia that most commonly occurs in the facial region as a dome-shaped or flat elevated nodule. MATERIALS AND METHODS: We studied the clinicopathologic and immunohistochemical characteristics of 19 cases of PLF. RESULTS: The patients comprised 11 females and eight men (mean age 44.9; age range 9-77 years). All cases were solitary except one case with multiple lesions. The lesions were located in the facial region except one that was located in the back. Histologically, there was a diffuse or nodular lymphoid infiltrate with hyperplastic and distorted hair follicles and occasionally enlarged eccrine units with a clear nuclear morphology. Immunohistologically, three cases showed predominantly B-cells, eight cases predominantly B-cells with numerous T-cells, six cases predominantly T-cells with numerous B-cells, and two cases predominantly T-cells. All lesions showed increased numbers of perifollicular dendritic cells expressing anti-S-100 protein and CD1a. DISCUSSION: PLF is a rare, benign, cutaneous lymphoid hyperplasia that may resemble cutaneous lymphoma. It has characteristic clinical and pathologic features showing abundant periadnexal S-100/CD1a -positive dendritic cells with dilated and activated pilosebaceous units. The lesion may resolve with complete excision or present spontaneous regression.

Sporadic progressive mucinous histiocytosis in a Mexican patient.

A 33 year-old woman presented with numerous 3- to 5-mm red-brown and yellow-brown dome-shaped nodules, primarily located on the scalp, dorsal aspects of the forearms, and lower extremities (Figure 1 and Figure 2). Her lesions started to appear 5 years prior to her consultation with increasing number and without spontaneous regression. Findings from a previous biopsy revealed epithelioid dermatofibroma. The remainder of the physical examination was unremarkable. There were no familial cases of this condition (both the mother and two older sisters were examined).

[National guidelines of diagnosis and treatment of the non-Hodgkin lymphoma]. / Guías nacionales de diagnóstico y tratamiento de linfoma no Hodgkin.

Non-Hodgkin lymphoma comprises a heterogeneous group of haematological malignancies, classified according to their clinic, anatomic-pathological features and, lately, to their molecular biomarkers. Despite the therapeutic advances, nearly half of the patients will die because of this disease. The new diagnostic tools have been the cornerstone to design recent therapy targets, which must be included in the current treatment guidelines of this sort of neoplasms by means of clinical trials and evidence-based medicine. In the face of poor diagnoses devices in most of the Mexican hospitals, we recommend the present diagnose stratification, and treatment guidelines for non-Hodgkin lymphoma, based on evidence. They include the latest and most innovative therapeutic approaches, as well as specific recommendations for hospitals with limited framework and therapy resources.

[Metastatic oropharyngeal squamous cell carcinoma in cervical lymph nodes associated to HPV infection type 16 and 45; clinical, morphological and molecular study of two cases]. / Carcinoma epidermoide orofaríngeo metastásico en ganglios linfáticos cervicales asociado a los subtipos 16 y 45 del virus del papiloma humano (VPH). Estudio clínico, morfológico y molecular de dos casos.

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma has been identified as a distinct entity within squamous cell carcinoma of the head and neck. In contrast to carcinomas associated with alcohol and/or tobacco, this subtype occurs at younger age, with frequent absence of classic risk factors, correlation with oral sexual habits, strong predilection for the palatial tonsils and the base of the tongue (lingual tonsils), basaloid or lymphoepithelial differentiation, higher degree of radiosensitivity, and overall better survival. We report two cases of lymph node, metastatic, poorly differentiated squamous cell carcinoma that were positive by immunohistochemistry for p16 with detection of HPV-16 and HPV-45 by PCR.

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.

[Poorly differentiated synovial sarcoma of the chest wall with rhabdoid features]. / Sarcoma sinovial pobremente diferenciado de pared del tórax con características rabdoides.

We report a rare case of a poorly differentiated synovial sarcoma (SS) with rhabdoid features. A 33-year-old woman was referred to our hospital with a chest wall tumor. MRI revealed a diffuse mass that invaded the pleura and extended into the esophagus, aorta, diaphragm and pancreas. Histopathological examination of the neoplasm showed it to be composed of sheets of small/medium cells with rhabdoid morphology, consisting of round, eccentrically localized nuclei, conspicuous nucleoli, and eosinophilic cytoplasm. Immunohistochemical studies demonstrated the tumor cells to be positive for TLE1, Bcl-2, EMA, CAM5.2, CD138 and CD56 and negative for desmin, smooth muscle actin or S100 protein. Fluorescent in-situ hybridization technique, performed on the paraffin section, showed SS18 gene rearrangement in the nuclei of the tumor cells. Poorly differentiated SS with "rhabdoid" features was diagnosed. This is only the 8th case of a SS with "rhabdoid" features reported to date.

Validation of HIV-1 MA Shell Structural Arrangements and Env Protein Interactions Predict a Role of the MA Shell in Viral Maturation.

The molecular structure of the type 1 human immunodeficiency virus (HIV-1) is tightly linked to the mechanism of viral entry. The spike envelope (Env) glycoproteins and their interaction with the underlying matrix (MA) shell have emerged as key components of the entry mechanism. Microscopy evidence suggests that the MA shell does not span the entire inner lipid surface of the virus, producing a region of the virus that completely lacks an MA shell. Interestingly, evidence also suggests that Env proteins cluster during viral maturation and, thus, it is likely that this event takes place in the region of the virus that lacks an MA shell. We have previously called this part of the virus a fusion hub to highlight its importance during viral entry. While the structure of the MA shell is in contention due to the unaddressed inconsistencies between its reported hexagonal arrangement and the physical plausibility of such a structure, it is possible that a limited number of MA hexagons could form. In this study, we measured the size of the fusion hub by analysing the cryo-EM maps of eight HIV-1 particles and measured the size of the MA shell gap to be 66.3 nm ± 15.0 nm. We also validated the feasibility of the hexagonal MA shell arrangement in six reported structures and determined the plausible components of these structures that do not violate geometrical limitations. We also examined the cytosolic domain of Env proteins and discovered a possible interaction between adjacent Env proteins that could explain the stability of cluster formation. We present an updated HIV-1 model and postulate novel roles of the MA shell and Env structure.

EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation.

Here, we report a retrospective series of 47 EBV-positive diffuse large B-cell lymphoma associated with advanced age. Histopathology allowed to the identification of different histological patterns: cases with polymorphic diffuse large B-cell lymphoma (29 cases), Hodgkin-like (8 cases) and polymorphic lymphoproliferative disorder-like (9 cases) patterns. One case was purely monomorphic diffuse large B-cell lymphoma. We show that this lymphoma type is a neoplasm with prominent classical and alternative nuclear factor-kB pathway activation in neoplastic cells (79% of the cases showed nuclear staining for p105/p50, 74% for p100/p52 and 63% for both proteins), with higher frequency than that observed in a control series of EBV-negative diffuse large B-cell lymphoma (χ(2) <0.001). Most cases showed an activated phenotype (95% non-germinal center (Hans algorithm); 78% activated B cell (Choi algorithm)). Clonality testing demonstrated IgH and/or K/Kde/L monoclonal rearrangements in 64% of cases and clonal T-cell populations in 24% of cases. C-MYC (1 case), BCL6 (2 cases) or IgH (3 cases) translocations were detected by FISH in 18% cases. These tumors had a poor overall survival and progression-free survival (the estimated 2-year overall survival was 40 ± 10% and the estimated 2-year progression-free survival was 36 ± 9%). Thus, alternative therapies, based on the tumor biology, need to be tested in patients with EBV-positive diffuse large B-cell lymphoma of the elderly.

[Immunohistochemical comparison between GCDFP-15 and estrogen and progesterone receptors in the diagnosis of metastatic carcinoma of the breast]. / Comparación inmunohistoquímica entre la GCDFP-15 y los receptores para estrógenos y progesterona en el diagnóstico de carcinoma metastásico de la mama.

BACKGROUND: In the workup of tumors of unknown primary origin in women, a frequent consideration is breast carcinoma, because it is common and may initially present as metastasis. OBJECTIVE: Describe and compare the immunohistochemical profile of hormonal receptors (estrogen receptor and progesterone receptor) and GCDFP-15 in lymph node metastatic breast carcinoma according the histological grade. METHODS: Retrospective study analyzing 30 patients with identified primary breast cancer and lymph node metastasis. The cases were divided in three groups: grade I (well differentiated), grade II (moderately differentiated) and grade III (poorly differentiated). We used three antibodies (estrogen receptor, progesterone receptor and GCDFP-15) in the lymph node and compare the expression according the histological grade. RESULTS: In metastatic lymph node from grade I breast carcinomas the hormone receptors were 100% positive and GCDFP-15 was 80% positive. In grade II, estrogen receptor and progesterone receptor were positive in 90 and 40% respectively, and GCDFP-15 was positive in 80%. In grade III, estrogen receptor and progesterone receptor were positive in 30 and 50% respectively, and GCDFP-15 in 60%. CONCLUSIONS: The immunohistochemical expression of hormonal receptors and GCDFP-15 in metastatic breast carcinoma is related to histological grade in the breast.