Histologic Diagnosis Of Lymphoma Research Articles

OUTCOMES OF PATIENTS WITH LYMPHOMA AND COVID‐19: AN OBSERVATIONAL COHORT STUDY FROM GELTAMO SPANISH GROUP

Introduction: COVID-19 is thought to be more frequent and severe in patients with cancer. Lymphoma patients may be especially vulnerable, due to the immunodeficiency and immune dysregulation caused by the lymphoma itself and the antitumor treatments. This study describes the characteristics and outcomes of lymphoma patients after developing COVID-19. Methods: This is a retrospective multicentre study carried out in the hospitals of the GELTAMO group, which included patients with a histological diagnosis of lymphoma and confirmed SARS-COV-2 infection before June 30th, 2020. The primary outcome was overall survival (OS) 60 days after a COVID-19 diagnosis. Results: A total of 218 patients (median sage 69.5 [21-94] years, 54% male) were included;100 patients had an indolent B-cell non-Hodgkin's lymphoma (NHL), 67 aggressive B-cell NHL, 19 mantlecell lymphoma, 15 peripheral T-cell lymphoma, and 17 Hodgkin's lymphoma. Patients had received a median of 1 line (0-7) of therapy, and 44.9% were on active treatment at the time of COVID-19 diagnosis. Only 6.4%, 1.8% and 0.9% of patients had received previously autologous stem-cell transplantation, allogeneic SCT and CAR-T cell therapy, respectively. 89% of patients were hospitalized, 71% required oxygen, and 15% mechanical ventilation. With a median follow-up of 91.5 days (13-203), 65 patients have died (60 from COVID-19, 4 from lymphoma, 1 due to other causes), with an estimated 60-day OS of 68.6% (95% CI 62.1-75.1) (figure 1A). In univariate analysis, baseline characteristics associated with decreased OS were age ≥70 years, hypertension, diabetes, other cancer, active disease and hypogammaglobulinemia, but only age ≥70 years maintained independent influence in the multivariate analysis (HR 3.29, 95% CI 1.86-5.83, p < 0.001). Active treatment did not significantly impact OS (figure 1B). Univariate analysis revealed different prognostic factors, apart from age, for patients with DLBCL (N = 60) and FL (N = 69). While the presence of active disease had a prognostic impact on DLBCL (60-day OS 56% vs 79%, p = 0.038) but not on FL (60-day OS 65% vs 78%, p = 0.181) patients, the opposite occurred in the case of active treatment, which seemed to have a negative influence only in patients with FL, as shown in figures 1C and 1D. Conclusions: Our results confirm a high mortality in patients with lymphoma and COVID-19, especially in those ≥70 years old. In patients with DLBCL, disease control seems essential to reduce the risk of mortality in the event of contracting the infection. By contrast, in patients with FL, delaying the start of treatment until it is not strictly necessary should be considered, and these patients should be prioritized to be vaccinated before starting antitumor treatment. This study provides initial data to develop recommendations for the management of lymphoma patients during the COVID-19 pandemic.

Misdiagnosis of tuberculosis in patients with lymphoma

Since 1970, the incidence of lymphoma, a potentially curable disease, has risen by 80% in the general population and in HIV- positive patients. Given its clinical similarities to tuberculosis (TB), lymphoma may be misdiagnosed and patients treated unnecessarily with potentially harmful TB medication. (i) To identify patients with a histological diagnosis of lymphoma who were previously misdiagnosed with TB; and (ii) to raise awareness of lymphoma as a differential diagnosis when TB has not been confirmed. A retrospective study was conducted at Ngwelezane Hospital in rural KwaZulu-Natal, which serves an estimated population of 3 million. Using clinic notes and a questionnaire for patients attending the lymphoma clinic, we identified patients who had undergone failed TB treatment in the 12 months before their histological confirmation of lymphoma. Twenty-one patients were included; 18 had been diagnosed with TB in the 12 months preceding the histological confirmation of lymphoma. All these patients subjectively reported TB treatment failure. Delay in diagnosing lymphoma or its misdiagnosis is an important clinical problem in South Africa, with the condition often misdiagnosed as TB. This subjects patients to incorrect treatment and potential harm. We propose an algorithm for the work-up of patients presenting with lymphadenopathy +/- constitutional symptoms, to assist diagnosis and management in resource-poor settings.

Evaluation of the University of Florida lomustine, vincristine, procarbazine, and prednisone chemotherapy protocol for the treatment of relapsed lymphoma in dogs: 33 cases (2003–2009)

To evaluate the toxicity and efficacy of a modification of a previously evaluated combination of lomustine, vincristine, procarbazine, and prednisone (LOPP) as a rescue protocol for refractory lymphoma in dogs. Retrospective case series. Animals-33 dogs with a cytologic or histologic diagnosis of lymphoma that developed resistance to their induction chemotherapy protocol. Lomustine was administered on day 0 of the protocol. Vincristine was administered on day 0 and again 1 time on day 14. Procarbazine and prednisone were administered on days 0 through 13 of the protocol. This cycle was repeated every 28 days. Median time from initiation to discontinuation of the University of Florida LOPP protocol was 84 days (range, 10 to 308 days). Overall median survival time was 290 days (range, 51 to 762 days). Overall response rate with this protocol was 61% (20/33), with 36% (12) having a complete response and 24% (8) having a partial response. Toxicosis rates were lower than for the previously published LOPP protocol. The University of Florida LOPP protocol may be an acceptable alternative to the mechlorethamine, vincristine, procarbazine, and prednisone protocol as a rescue protocol for dogs with lymphoma.

Heteroduplex Polymerase Chain Reaction is Essential for Canine Receptor Rearrangement Analysis

Polymerase chain reaction (PCR) for antigen receptor rearrangement is a sensitive technique for detecting lymphocyte-proliferative disorders, but it tends to produce false-positive results, a phenomenon termed pseudoclonality. Heteroduplex analysis, which is useful to distinguish clonal reactions from pseudoclonal ones in dogs, can be applied to avoid misdiagnosis and determine the reliability of results. In the current study, PCR for antigen receptor rearrangement was used to identify clonal proliferation of lymphocytes in duodenal and lymphoid tissue from dogs presenting with chronic vomiting and enlarged peripheral lymph nodes typical of multicentric lymphoma, and the test results were verified with heteroduplex analysis. In the case of almost all of the duodenal samples, even without a histologic diagnosis of lymphoma, a distinct band similar to that observed in the case of lymphoma was obtained for both B- and T-cell clonality. All of the bands obtained from the nonneoplastic duodenum disappeared following heteroduplex analysis of the PCR product, whereas the distinct bands from the lymphoma remained. In the lymph node samples, the pseudoclonal bands that disappeared in the heteroduplex analysis were detected mainly in B cells. In conclusion, heteroduplex analysis with PCR for antigen receptor rearrangement is a suitable tool for diagnosing canine lymphoma and decreasing the possibility of misdiagnosis of pseudoclonality.

Optimized Processing of Fine-Needle Lymph Node Biopsies for Automated Immunostaining

A straightforward, reliable technique for postcollection processing and evaluation of cytologic specimens for antigen detection using an automated immunostainer was developed. Visual assessment of cell suspension turbidity was used in parallel with light microscopic examination of concentrated cytospin preparations to verify the diagnostic utility of samples for immunocytochemical staining. Fine-needle lymph node biopsies from 81 dogs with lymphadenomegally and a cytologic or histologic diagnosis of lymphoma were introduced into ethylenediamine tetra-acetic acid tubes containing standardized storage media. Cell suspension turbidity was assessed to estimate cell concentration and resultant volume required for cytospin preparations with optimal cellularity. Preliminary cytospin preparations (using estimated volumes based upon turbidity) were stained using modified Wright stain and examined microscopically for intact neoplastic cell concentration. Once an optimal volume for cytospin preparations was established, additional concentrated slides were prepared for immunophenotyping, using an automated immunostainer and antibodies specific for cluster of differentiation (CD)79a and CD3e. All cell suspension samples with adequate gross turbidity had ample intact neoplastic cell concentration for immunocytochemical staining. Based on CD79a and CD3e expression, 51 (63%) B cell, 19 (23%) T cell, 3 mixed T and B cells (4%), and 3 non-T- and non-B-cell lymphomas (4%), as well as 5 (6%) nondiagnostic samples were identified. Three out of 5 of the nondiagnostic samples were submitted early in the investigation prior to the establishment of gross specimen turbidity guidelines. Immunocytochemical staining results were in complete agreement with all 6 available immunohistochemical correlates. The ability to visually assess sample adequacy prior to sample submission may encourage more widespread use of immunocytochemical techniques.

Amyloïdome associé à un lymphome du Malt pulmonaire primitif

Pulmonary amyloïdoma is a nodular formation containing amyloid deposits, which can mimick a pulmonary carcinoma. Its etiologic diagnosis require the search of an underlying infectious disease, a connective tissue disorder or a lymphoma. We report the case of a 73 year old woman, asymptomatic, presenting an incidental pulmonary opacity in the left upper lobe, associated with hilar lymphadenopathies, positive on PET scan. The patient underwent a left superior lobectomy with mediastinal lymphadenectomy. Histologically, the nodule was composed of amylodosis deposits. It was surrounded by a dense lymphoïd infiltrate. The phenotype (CD20+, CD5-, CD3-, CD23-) of the lymphoïd cells, like the demonstration of a lambda light chain restriction permited to pose the diagnostic of pulmonary Malt lymphoma and to characterize the AL lambda type of the amyloïdosis Association of amyloïdoma and Malt lymphoma is a rare condition. The histologic diagnosis of lymphoma may be difficult in this case, the lymphomatous process being concealed by the volume of the amyloïd mass. Therefore it is necessary in case of amyloïdoma to search histological signs of Malt lymphoma and to confirm diagnosis by demonstrating a B clonality and a immunoglobulin light chains restriction.

When is a mediastinal mass critical in a child? An analysis of 29 patients.

The aims of this study were to determine the pattern of presentation of childhood mediastinal masses in our community and to identify factors associated with the development of acute airway compromise. The authors retrospectively reviewed the records of 29 consecutive patients with mediastinal masses managed at their institution between January 1995 and December 2001. Demographic data, mass characteristics, clinical presentation, and surgical procedures were recorded. Seven patients (24.1%) were asymptomatic at presentation. Eight (27.6%) were classified as having acute airway compromise at presentation. Respiratory symptoms and signs were the most common mode of presentation (58.6% and 55.2%, respectively). The most common histological diagnosis was neurogenic mass (37.9%), followed by lymphoma (24.1%). Most masses were located in the superior mediastinum (41.1%). Factors associated with the development of acute airway compromise were (1) anterior location of the mediastinal mass (P=0.019), (2) histological diagnosis of lymphoma (P=0.008), (3) symptoms and signs of superior vena cava syndrome (P=0.015 and 0.003, respectively), (4) radiological evidence of vessel compression or displacement (P=0.015), (5) pericardial effusion (P=0.015), and (6) pleural effusion (P=0.033). Clinical presentation of childhood mediastinal masses is often nonspecific or incidental. Yet they have the propensity of developing acute airway compromise, which is closely associated with superior vena cava obstruction. Such patients should be managed as a complex cardiorespiratory syndrome, termed "critical mediastinal mass syndrome", by an experienced multidisciplinary team.

Gene rearrangement of immunoglobulin as a marker of thyroid lymphoma.

Thyroid lymphoma occurs most commonly in the thyroid gland in association with Hashimoto's thyroiditis. Histologic findings occasionally cannot distinguish lymphoma from Hashimoto's thyroiditis, which creates a serious problem of whether treatment should be initiated. For this study, we examined 33 lymphoma tissues and 10 thyroid tissues from patients with Hashimoto's thyroiditis for the presence of gene rearrangement of immunoglobulin, which represents clonality of B-cell-derived tumors. Genomic DNA from thyroid tissues was digested with Bam H1 and Hind III restriction enzymes followed by electrophoresis. A Southern blot was performed with an IgH-JH probe or IgL-J kappa probe to detect gene rearrangement. Of the 33 lymphoma tissues, 27 (85%) showed gene rearrangement of immunoglobulin, whereas none of Hashimoto's thyroiditis tissue showed gene rearrangement. Five patients with a positive histologic diagnosis of lymphoma showed a negative gene rearrangement and were treated as having lymphoma. We encountered one case of lymphoma (plasmacytoma) in which gene rearrangement (not histologic findings) was diagnostic. Gene rearrangement of immunoglobulin can be used to detect thyroid lymphoma, particularly when the histologic diagnosis is inconclusive. The sensitivity of detecting thyroid lymphoma by the Southern blot method was about 85% in the present series.

Small bowel malignant lymphoma complicating celiac sprue and the mesenteric lymph node cavitation syndrome

Malignant small intestinal lymphoma may complicate or antedate clinical recognition of celiac sprue. However, histologic diagnosis of lymphoma is made especially difficult in the presence of small bowel ulceration. A 70-yr-old man with celiac sprue and a history of dermatitis herpetiformis was initially seen for recurrent diarrhea; panmalabsorption with steatorrhea and protein-losing enteropathy were documented. Subsequent studies showed ectopic gastric mucosa in the small bowel, hyposplenism with mesenteric lymph node cavitation, and small bowel erosions and ulceration. Despite strong clinical suspicion for more than 2 yr, only 1 of 88 small bowel biopsy specimens was positive for lymphoma. At autopsy, shortly after histologic diagnosis of lymphoma, extensive small bowel involvement and infiltration were observed. This is the first report of lymphoma complicating the recently described nonneoplastic lymphoreticular syndrome associated with celiac sprue characterized by splenic atrophy and mesenteric lymph node cavitation.

Diagnosis of B cell lymphoma by analysis of immunoglobulin gene rearrangements in biopsy specimens obtained by fine needle aspiration.

Histologic diagnosis of lymphoma is far more difficult in the disaggregated cells obtained by percutaneous aspiration of lymph nodes than in tissue sections prepared from excisional biopsy specimens. However, the simplicity, economy, and safety of aspiration biopsy makes this an attractive diagnostic option in certain situations. In the present study, we demonstrate that lymph node aspirates provide material that is both suitable and sufficient for accurately detecting clonal proliferations of B cells by analysis of immunoglobulin gene rearrangements. The rearrangements detected in aspirated tissue serve as clonal markers that can be directly compared with the rearrangements found in histologically confirmed lymphoma removed by open biopsy. The application of gene rearrangements to aspirated material therefore offers a useful method of diagnosing lymphoma, particularly for the purposes of more thorough staging at initial presentation or the evaluation of tissues for possible relapse.

Has primary gastric lymphoma become more common?

Primary gastric lymphoma comprised 20% of 119 patients with gastric malignancy seen at our hospital between 1975 and 1980, even when strict criteria were applied to exclude systemic lymphoma patients with gastric involvement. Of the 24 patients with gastric lymphoma, 16 had disease confined to the stomach and contiguous nodes. Eight with massive stomach involvement, but also evidence of distant disease were classified as "probable" primary gastric lymphoma. Symptoms, physical findings, and laboratory studies in the lymphoma patients were similar to those of carcinoma patients. Radiography was more likely to suggest benign conditions in cases with lymphoma. While endoscopy suggested malignant disease in over 80% of lymphoma patients, histologic diagnosis of lymphoma was made first by endoscopy in only 38%. Our data suggest that lymphomas are more common among gastric neoplasms than reported in the past. This cannot be accounted for by referral patterns or by improvement in diagnostic techniques. Although lymphomas appear to be more common, this is not necessarily due to a rise in their incidence. The proportionate increase in lymphomas may be due to the decline in gastric carcinoma or to a true increase in incidence.

Monitoring the response of lymphoma patients to therapy: correlation of abdominal CT findings with clinical course and histologic cell type.

A review was made of 365 abdominal computed tomographic (CT) examinations in 125 patients with a histologic diagnosis of lymphoma who had undergone CT before and after therapy. Clinical correlation immediately preceding the follow-up CT examination was obtained in 100 patients. In these 100 patients, five distinct subgroups emerged: (a) reduction in extent of disease without changes in internal nodal characteristics; (b) reduction in extent of disease with change in internal nodal characteristics; (c) no change in extent of disease and no change in internal nodal characteristics; (d) no change in extent of disease but change in internal nodal characteristics; and (e) disease progression. Changes in internal nodal architecture consisted of diminished attenuation or mesenteric "stranding." A 91% correlation existed between the CT findings and the clinical course. Of those patients with a worsening clinical course, and follow-up CT studies suggesting a stable or improved response to therapy, relapse in the majority (57%) involved the central nervous system. The authors conclude that limited abdominal CT examination is satisfactory in the posttherapy follow-up of lymphoma patients.

High incidence of pericardial effusion in non-Hodgkin's lymphoma: Usefulness of echocardiography

In a consecutive group of patients with non-Hodgkin's lymphoma a prospective study was designed to detect pericardial and myocardial abnormalities at presentation for initial clinical staging. Thirty-two patients, ranging from 15 to 65 (mean, 46) years of age, were studied. Twenty-six (81%) were in Stages III and IV. Echocardiographic examination revealed that 17 patients (53%) had pericardial effusion (PE). Four subjects with lymphoblastic lymphoma and extensive mediastinal involvement had clinical and echographic signs of cardiac-tamponade. In 5 cases, pericardiocentesis was performed; abnormal lymphoblasts were demonstrated in 4. In one of these, the histological diagnosis of lymphoma was performed from analysis of the PE. The follow-up ranged from 3 to 32 (mean, 12.3) months. There was no difference in the survival rates whether or not PE was present: 70 and 68% respectively at 1 yr. No patient required intracavitary chemotherapy or surgery. We conclude that PE in advanced non-Hodgkin's lymphoma with large mediastinal masses is frequent. Once tamponade is treated, the presence of PE has no adverse effect on survival at 1 yr.

The radiological features of gastric lymphoma

Primary gastric lymphoma accounts for 2.5% of all malignant gastric neoplasms. The clinical, macroscopic, and radiological appearances frequently resemble those of other gastric lesions, notably carcinoma. However, the prognosis of lymphoma is much better and accurate diagnosis is therefore important. The prognosis of secondary gastric lymphoma is less good but its accurate recognition is still important. Conventional radiology is a key investigation and the radiological appearances have been reviewed in 18 patients with a histological diagnosis of lymphoma. 5 of these were already known to have lymphoma elsewhere. The radiological appearances were similar whether or not there was lymphoma elsewhere. There is no single accurate pattern of recognition but the following features occurred often enough to be useful pointers: (a) Distensible stomach in the presence of a mass. (b) Mucosal hypertrophy in the presence of a mass. (c) Mucosal hypertrophy associated with large gastric ulcer or multiple gastric ulcers. (d) Contiguous spread of abnormality into the duodenal cap. (e) Duodenal ulceration associated with gastric mass. (f) The youth of the patient. The reported incidence of primary lymphoma of the stomach is 2.5% of all malignant gastric neoplasms ( Welborn et al., 1965 ). Similarly about 2.5% of lymphomas present with a primary lesion in the stomach ( Bush and Ash, 1969 ). Its very rarity leads to difficulty in recognition and at laparotomy it may resemble an inoperable carcinoma ( Salmela, 1968 ). However, the prognosis of lymphomas is much better than that of carcinoma ( Jenkinson et al., 1954 , Jordan et al, 1955 ) even when regional lymph nodes are involved ( Friedman, 1959 ), and the treatment of choice is resection followed by radiotherapy ( Friedman, 1959 ). Therefore accurate pre-operative diagnosis is important. Secondary lymphoma of the stomach occurs more often than the primary form ( McNeer and Berg, 1959 ) but is still uncommon, and occurs in up to 3.5% of patients known to have lymphoma ( Rosenberg et al, 1961 : Block, 1967 ). The prognosis is not as good as in the primary form ( Snoddy, 1952 ), but early recognition of gastric involvement is still important so that appropriate local treatment can be undertaken ( Burnett and Herbert, 1956 ). The diagnosis of both forms of the disease has proved difficult from clinical features ( Sherrick et al., 1965 ) and from radiological studies ( Jenkinson et al., 1954 ; Jordan et al., 1955 ). The most optimistic estimate of a 50% success rate was obtained after combined clinical, radiological and gastroscopic examination ( Palmer, 1950 ). Radiological studies remain the most important investigation ( Ochsner and Ochsner, 1955 ), but have proved disappointing. 18 consecutive cases of proven lymphoma of the stomach have been reviewed to seek a reliable pattern of recognition.