The aim was to evaluate the cellular immune response in atypical tuberculosis and granulomatous inflammation consistent with tuberculosis (TBC), negative histochemically for acid-fast bacilli and analysed by PCR for Mycobacterium tuberculosis (MT) detection in paraffin-embedded tissue. Thirty six samples of differently localized atypical tuberculous lesions and granulomatous tuberculoid lesions negative for acid fast bacilli and 4 positive cases on Ziehl-Nielsen stain were analysed by PCR for MT detection and were tested immunohistochemically (IHC) for the cellular immune response in the granulomas and perigranulomatous tissue. The samples selected were: 7 pulmonary and 33 extrapulmonary specimens, especially lymph nodes. Histologically, the atypical tuberculous lesions contained supurative necrosis, defective granulomas and cellular polymorphism. The epithelioid cells showed frequent mitoses. The immunoprofile of cells was polymorphous. L26 positive small lymphocytes were found in nodular lymphoid aggregates surrounding granulomas. A significantly increased number of positive UCHL1 cells were found in 33 out of the 40 analysed cases, with a larger percentage of CD4 positive T cells (81.8% of cases). CD44 was positive in multinucleated giant cells (17.5% of cases), epithelioid cells (60% of cases) and lymphocytes (30% of cases). CD68 was localized in multinucleated giant cells and epithelioid cells, in a 4%, respectively 62.5% of cases. The PCR was performed in all 40 cases; the tissue samples were heterogeneous (lung, lymph nodes, lever, nasopharynx, etc.) and needed a good quality extraction of DNA. Performing a control PCR for Beta Globin tested the extraction; a good result was obtained in 31 cases (77.5%); from these, 19 cases had amplification for IS 6110. The cellular immune response in the atypical tuberculous lesions was similar in cases with and without acid-fast bacilli, but positive for PCR. In the most cases with negative PCR reaction, it was due to a deficient fixation of the material. The T lymphocytes were numerous in all types of tuberculous granulomas, with the prominence of CD4 positive subtype. The immunoprofile of the epithelioid cells, positive for CD44 and CD68, presenting frequently mitoses suggests an activate state in a possible relationship to the T-cell-mediated immune response in tuberculosis.
Diffuse large B-cell lymphoma (DLBCL) accounts for about 30% of non-Hodgkin’s lymphoma (NHL) cases. The 2008 WHO Classification of Lymphoid Neop lasms recognizes several clinicopathological varian ts, subtypes and distinct disease entities of DLBCL. We present a review of clinical, pathological and mol ecular factors with implication in DLBCL behavior. Even if the golden standard therapy for CD20-positive DLBC L is still represented by R-CHOP, prognostic factor asse ssment could open new therapeutic perspectives.
Diffuse large B-cell lymphoma (DLBCL) represent the most frequently non-Hodgkin's lymphoma (NHL) (over 30%), especially in developing countries. Many associations of NHL with another neoplasia were described following chemotherapy or radiotherapy regimens. The coexistence of DLBCL with myeloproliferative neoplasms (MPNs) JAK2V617F positive at the onset was very rare reported in the literature. We describe a clinical case of a 52-year-old man who presented both diagnoses at the onset - DLBCL and MPN - polycythemia vera (PV) type. The patient was treated with two CHOP cycles (Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisolone) followed by six R-CHOP (Rituximab-CHOP) cycles, together with a platelet-reducing agent, achieving remission for 20 months, followed by a relapse which is under treatment. The clonally expansion of an abnormal pluripotent hematopoetic stem cell could be responsible for both, PV and DLBCL. However, recent reports suggested the possible involvement of two different clones. The clinical significance and the role of JAK2 mutation in the evolution of patients with NHLs, including DLBCL are still unknown. Further genetic and clinical studies have to point out common gene mutations for the two diseases and their connection with the diseases behavior under the treatment.The coexistence of NHLs and especially DLBCLs and MPNs JAK2 positive is very rare. Although DLBCL alone has good prognosis, other prognostic factors should be checked when it is associated with PV. The presence of JAK2V617F seems to be a candidate but whose role in DLBCL evolution, natural or under treatment has to be cleared up.
During the last two years, the COVID-19 pandemic led to millions of disease-related deaths worldwide. The efforts of the scientific community facing this global challenge resulted in outstanding achievements. Thus, within one year, new mRNA-based vaccines against SARS-CoV-2 viral infection were released, providing highly efficient protection and showing a very good safety profile in the general population. However, clinical data collection after vaccination is a continuous process for the long-term safety of any new medical product. The aim of our paper is to present two cases of hematological malignancies: diffuse large B-cell non-Hodgkin lymphoma and T/NK-cell lymphoma, diagnosed shortly after the administration of the mRNA COVID-19 vaccine.
We present the case of a 62 year old male with no relevant medical history, who for the last two months had been complaining of dysphagia for solids and liquids, marked physical fatigue, oliguria. Clinical examination revealed palor and dehydrated skin, as well as a tumoral mass of 10/10 cm palpable in the upper abdomen. Upper digestive endoscopy was performed, showing a vegetant lesion of 6 cm on the gastric angle, with a central ulcer of 4 cm. The oesophagus and duodenum were normal, and Helicobacter pylori test was negative. Histological exam from the gastric lesion revealed diffuse large-cell malignant lymphoid tumoral proliferation, with tumoral cells infiltrating the mucosa between the glands. Immunohistochemical analysis diagnosed B cell lymphoma. CT scan of the thorax, abdomen and pelvis was performed, revealing multiple tumors involving the gastric walls, the posterior parietal peritoneum, the intra-peritoneal fat, the pancreatic tissues and the right antero-inferior mediastinum, as well as multiple adenopathies on both sides of the diaphragm and ascites. We performed paracentesis, and malignant cells were detected in the peritoneal fluid. Bone marrow biopsy was normal. The patient was referred to the hematology department for treatment. He received chemotherapy including CHOP followed by RICE with the disappearance of the gastric tumor on upper endoscopy and the disappearance of peritoneal, mediastinal and pancreatic region tumors with the persistence of a circumferential thickening of the horizontal gastric region walls on CT reevaluation.
Background: Brentuximab Vedotin (BV) has revolutionized the treatment landscape for Hodgkin’s lymphoma, yet its effects on pre-existing autoimmune disorders remain elusive. Methods: Here, we present four cases of patients with concurrent autoimmune conditions—Crohn’s disease, vitiligo, type I diabetes, and minimal change disease—undergoing BV therapy for Hodgkin’s lymphoma. The patients were treated with A-AVD instead of ABVD due to advanced-stage disease with high IPI scores. Results: Our findings reveal the surprising and complex interplay between BV exposure and autoimmune manifestations, highlighting the need for multidisciplinary collaboration in patient management. Notably, the exacerbation of autoimmune symptoms was observed in the first three cases where T-cell-mediated autoimmunity predominated. Additionally, BV exposure precipitated autoimmune thrombocytopenia in the vitiligo patient, underscoring the profound disruptions in immune regulation. Conversely, in the minimal change disease case, a disease characterized by a blend of B- and T-cell-mediated immunity, the outcome was favorable. Conclusions: This paper underscores the critical importance of vigilance toward autoimmune flare-ups induced by BV in patients with concurrent autoimmune conditions, offering insights for tailored patient care.
Granulomas are encountered in 1-2% of biopsies performed in various hematological and non-hematological diseases. Almost 50% of bone marrow granulomas are associated with infections and 25% with hematologic disorders, especially lymphoma and multiple myeloma. Toxoplasmosis is reported to induce granulomas in bone marrow inmunosuppressed patients. On the other side, long-term unexplained remissions after conventional treatment in multiple myeloma were mentioned in up to 10% of cases.A 56-years-old female patient was diagnosed with IgG(kappa) multiple myeloma in 1992. After 5 years, being still in complete remission, frequent bone marrow epithelioid non-caseating granulomas were noticed in biopsy, without clinical symptomatology or modifications of routine paraclinical examinations. The history revealed no treatments with antiarrhythmic, antihypertensive, anticonvulsivants or nonsteroid antiinflammatory drugs. The serologic tests for other infections or systemic diseases known to induce granulomas were negative, except those for toxoplasma gondii IgG. The treatment with azithromycine and pyrimethamine induced the disappearance of granulomas, simultaneously with an important decrease of anti-toxoplasma IgG antibodies titer.The bone marrow granulomas provide a valuable histologic clue to opportunistic infections and the bone marrow biopsy is useful for their diagnosis. In the specific case of toxoplasmosis, a recently proposed treatment with azithromycin induced the resolution of the granulomas. Due to the usual lack of specificity of the most bone marrow granulomas, a broad and long-term clinical, histopatological and serological follow-up to establish the etiology should be performed.
