Clinical mimics of lymphoma

Lymphadenopathy is a common clinical finding and is frequently benign. Warning signs suggestive of a malignant etiology include lymph nodes >2 cm in size, supraclavicular location, and generalized lymphadenopathy associated with hepatosplenomegaly or systemic symptoms. A metastatic solid tumor is always in the differential diagnosis of localized lymphadenopathy, particularly in older individuals. In the case of more generalized lymphadenopathy, in addition to the more common lymphomas, benign etiologies as well as benign and atypical lymphoproliferative disorders need to be considered. Benign etiologies of lymphadenopathy can include infections, autoimmune disorders, drug hypersensitivity reactions, sarcoidosis, and amyloidosis. Rare but benign lymphoproliferative disorders include Kikuchi's disease, Rosai-Dorfman disease, and progressive transformation of germinal centers. Atypical lymphoproliferative disorders that bear close surveillance for evolution to a more aggressive malignancy include Castleman's disease, lymphomatoid granulomatosis, and lymphomatoid papulosis. Previously considered in this category but now classified as a true lymphoma is angioimmunoblastic lymphadenopathy with dysproteinemia. Physicians need to be aware of all of these disorders when evaluating suspicious lymphadenopathy, while also considering the more common lymphomas and leukemias.     

Non-Hodgkin's lymphoma in patients with systemic lupus erythematosus

Two cases of non-Hodgkin's lymphoma (NHL) associated with systemic lupus erythematosus (SLE) are described. Patient-1 was a 65-year-old woman in whom SLE and diffuse large B-cell lymphoma were concurrently diagnosed. The patient presented with low-grade fever, butterfly rash, arthritis and generalized lymphadenopathy without splenomegaly or bone marrow involvement. Complete remission of NHL and SLE was achieved with cyclophosphamide, adriamycin, vincristine and prednisone. Patient-2 was a 56-year-old woman in whom SLE had been diagnosed 14 years earlier. The patient presented with low-grade fever, bulky splenomegaly without lymphadenopathy, IgM λparaproteinemia, and expansion of a monoclonal CD19 + /CD22 + λ-type B-cell population in both bone marrow and peripheral blood. Diagnosis of a lympho-plasmacytoid lymphoma was established histologically after splenectomy. A partial remission of the neoplasm was achieved with cyclophosphamide, vincristine and prednisone. We suggest that the development of NHLs in patients with SLE may not be coincidental and we recommend the search for NHL in cases of SLE with prominent lymphadenopathy, massive splenomegaly or expansion of a monoclonal CD19 + /CD22 + B-cell population.     

A case of adult T-cell leukemia achieving complete remission with epirubicin, vincristine and prednisolone chemotherapy

A 68-year-old man was referred to our hospital because of generalized lymphadenopathy. His abnormal findings were hepatomegaly, leukocytosis and elevated serum LDH. Anti-ATLA antibody was positive. As about half of the peripheral lymphocytes reacted to the monoclonal antibody CD25, these cells were considered to be compatible with ATL cells having an interleukin-2 receptor. Initially, recombinant beta-interferon was administered, but it was not effective. A combination of vincristine (VCR) and prednisolone (PDN) was partially effective against the lymphadenopathy, but the hepatomegaly and leukocytosis did not improve. 4'-epi-Adriamycin (Epirubicin), at a doses of 20 mg/body, weekly, was subsequently added to VCR + PDN therapy. The patient achieved complete regression 2 months later, and has been in continuous complete remission for more than 3 months.     

Successful treatment of angioimmunoblastic lymphadenopathy with dysproteinemia with cyclosporin A.

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a lymphoma-like disease. Although the histologic appearance of this disease is benign, it is clinically malignant, with chemotherapy being ineffective and the prognosis being poor. In this article, the authors report the results of treating two patients with AILD with cyclosporin A. One patient had cervical lymphadenopathy and fever, and AILD was refractory to both chemotherapy and alpha-interferon. However, treatment with cyclosporin A achieved complete remission. The other patient had generalized lymphadenopathy, and cyclosporin A was used as the treatment of first choice. Complete remission also was achieved in this patient, who still is in remission. These two cases demonstrate that cyclosporin A can be effective for treating AILD.     

Generalized lymph node metastasis of early uterine cancer in an HTLV-I carrier

Generalized lymphadenopathy due to metastases of keratinizing squamous cell carcinoma developed in a 68-year-old woman who was a carrier of human T-cell leukemia Type I (HTLV-I). On her 74th hospital day, she died of massive metastases of the superficial and deep-seated lymph nodes, thyroid, lungs, pleura, liver, spleen, pancreas, kidneys, and retroperitoneum. At autopsy, the primary tumor was found in the uterine cervix. The depth of stromal invasion was approximately 4.0 mm. Such an extensive dissemination usually does not occur in cervical cancer with this type of early stromal invasion. It is conceivable that the chronic HTLV-I infection compromised the immunosurveillance against cancer and accelerated progression of the disease in this patient.     

Primary bone marrow T-cell anaplastic large cell lymphoma with triple m gradient

We present a case of a 60-year-old male patient with primary bone marrow anaplastic large cell lymphoma. He was admitted to the hospital with the symptoms of anemia and fever. There was no evidence of lymphadenopathy or splenomegaly. Immunoelectrophoresis showed the presence of a triple M gradient (double IgM and an IgG), with the IgG and one of the IgM paraproteins functioning as a cryoglobulin. The patient had no hepatitis C virus infection. Bone marrow biopsy showed massive CD30-positive, ALK-negative large lymphoid cell infiltration of T-cell origin with anaplastic morphology. PCR analysis of lymphoid cells separated from the bone marrow demonstrated the presence of a B/T hybrid genotype disorder with no evidence of the t(2;5), nor t(1;2) translocations. The patient entered a period of remission following CHOP chemotherapy. The patient subsequently died of sepsis as a consequence of serious humoral immunodeficiency.     

A Rare Case of “Rosai–Dorfman Disease”

Sinus histiocytosis with massive lymphadenopathy (SHML) is a benign proliferating histiocytic disorder, predominantly of lymphnodes with extranodal involvement also seen. We present a case of 35 years old female with history of multiple swellings in neck since 1 month duration. On examination patient had painless bilateral cervical lymphadenopathy. No other ENT manifestations noted. Lymphnode biopsy revealed SHML. Abdominal scan and chest X-ray was done which was normal. This case report highlights the clinical, histological aspects of SHML, Rosai–Dorfman disease.     

Case of immunoblastic sarcoma (IBS)

A patient with immunoblastic lymphadenopaty which evolved into immunoblastic sarcoma is reported. A 48-year-old female was admitted to our department because of cough and fever. A diagnosis of immunoblastic lymphadenopathy had been made two years before the present admission. Physical examination revealed generalized lymphadenopathy. Chest radiograms showed a left hilar mass. The pulmonary tumor and enlarged lymphnodes were treated by irradiation. Although there was marked improvement at first, she experienced several relapses. One year after the admission, chest radiograms showed multiple pulmonary lesions. She developed pancytopenia and bone metastases. At autopsy, the lymphnodes showed histological evidence of immunoblastic sarcoma; a pulmonary lesion showed immunoblastic lymphadenopathy.     

Lymphadenopathic type of Kaposi's sarcoma presenting with generalized petechial hemorrhages. A case report from Taiwan

An 8-year-old Taiwanese girl presenting with generalized petechial hemorrhages, severe thrombocytopenia and lymphadenopathy was found to have primary Kaposi's sarcoma of lymph node without cutaneous involvement. This patient is a first-documented case of lymphadenopathic type of Kaposi's sarcoma in Taiwan. The associated severe thrombocytopenia resulting in generalized petechial hemorrhages as the initial manifestation is also unique in this case.     

Marked Retroperitoneal Lymphadenopathy in Hairy Cell Leukemia: A Case Report

Hairy cell leukemia (HCL) is uncommonly associated with lymphadenopathy, while retroperitoneal lymphadenopathy is extremely uncommon. We report on a patient with a 12-year history of HCL who developed painless jaundice and ascites, accompanied by positional discomfort with persistent nausea. Computed tomography examination revealed 2 large retroperitoneal masses, which at autopsy consisted of HCL with focally intermixed pancreatic and peripancreatic tissue. Lymphadenopathy was not identified above the diaphragm or below the aortic bifurcation. No vasculitis or an unusual HCL histology was identified. As previous reports, our findings suggest that HCL with massive lymphadenopathy has a specific site predilection, but it is not necessarily accompanied by vasculitis or an unusual histology.Key words: Hairy cell leukemia, Retroperitoneal lymphadenopathy     

Angioimmunoblastic lymphadenopathy with dysproteinemia following doxycycline administration

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a primary lymphoproliferative T-cell disorder, currently classified as a peripheral T-cell non-Hodgkin's lymphoma. AILD is characterized by generalized lymphadenopathy, hepatosplenomegaly, immunological abnormalities, polyclonal hypergammaglobulinemia and anemia. We report a case of AILD in an 80-year-old male who presented with a generalized pruritic maculopapular eruption and fever following doxycycline administration. The maculopapular rash progressed to formation of confluent nodules, plaques and finally erythroderma with lymphadenopathy and hepatosplenomegaly. Blood analysis revealed an elevated erythrocyte sedimentation rate and polyclonal hypergammaglobulinemia. Lymph node biopsy showed almost complete effacement of the nodal architecture with diffuse proliferation of small vessels forming an arborizing network, surrounded by atypical lymphocytes, usually CD3+ CD4+ and occasionally CD3+ CD8+. There were also larger cells (immunoblastic shape) that displayed CD20 positively, some scattered plasma cells, and eosinophils. Histology of a cutaneous lesion showed spongiosis and infiltration of the epidermis by atypical lymphocytes with large hyperchromatic nuclei, perivascular dermal lymphocytic infiltrate (CD3+) mixed with plasma cells and occasional large immunoblasts (CD20+). During hospitalization the patient developed hemolytic anemia (Coombs positive) and lung metastases. The prognosis of AILD is generally poor, with a median survival of less than 20 months. Our patient died two and a half months after the diagnosis was made due to sepsis caused by Staphylococcus aureus isolated in hemoculture.     

High-grade mantle zone lymphoma

A 66-year-old man with a 6-month history of sweating at night, generalized lymphadenopathy, hepatosplenomegaly, and paraproteinemia was diagnosed to have a Stage IV mantle zone lymphoma (MZL), which behaved aggressively. The neoplasm rapidly disseminated to extranodal sites--the skin, lungs, pleural cavity, and the central nervous system. The neoplasm did not respond to initial double-agent chemotherapy, but it did partially respond to multi-agent chemotherapy. In addition, the neoplasm had histopathologic features not reported previously in MZL--vascular invasion, massive extranodal infiltration, high mitotic count, and convoluted nuclei.     

Unusual IgD+/CD38-follicular lymphoma with leukemic presentation

Follicular lymphoma (FL) is a low-grade lymphoma, with rare presentation of leukemic phase in peripheral blood at the diagnosis. We describe a 49-yr-old woman who developed leukemic phase of FL in a 3 mo period after histological diagnosis of peripheral lymph node. To confirm the final diagnosis, flow cytometry (FCM) of peripheral blood, nested PCR with bcl-2 rearrangement, and cytogenetic analysis of peripheral blood and bone marrow cells were done. Lymphoma cells were negative for CD38 and expressed monoclonal surface immunoglobulins with relatively strong and “bright” IgD and “dim” kappa-chain by FCM analysis. Although the patient presented with generalized lymphadenopathy, massive peripheral blood and bone marrow involvement, she achieved complete clinical response after first-line chemotherapy COP and rituximab. She is still in a good condition with follow up over 2 yr.     

Rosai-Dorfman disease. Extranodal sinus histiocytosis in three co-existing sites. A case report

A 73-year-old woman presented with mild anterior uveitis, ipsilateral optic neuropathy, and ipsilateral skin nodules. A compressive mass at the level of the orbital apex and sphenoid wing was found on cranial magnetic resonance imaging. Biopsy of the skin nodules revealed histopathologic evidence of sinus histiocytosis with massive lymphadenopathy, or Rosai–Dorfman disease (RDD). Systemic investigations failed to show any massive lymphadenopathy, making this a case of extranodal RDD. This is a salient case in that it proposes three simultaneous and separate sites of involvement by extranodal RDD. It also exemplifies that RDD should be a suspect diagnosis even in the absence of lymphadenopathy.     

Extranodal rosai-dorfman disease with cutaneous and periodontal involvement: a rare presentation

Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease (RDD) was first described as a distinct clinicopathological entity by Rosai and Dorfman in 1969. SHML is commonly characterized by painless cervical lymphadenopathy, and its clinical course is generally benign and self-limiting. This disorder commonly involves the lymph nodes but may secondarily involve the skin. However, purely cutaneous disease without lymphadenopathy or internal organ involvement rarely occurs. In the absence of the massive lymphadenopathy that is characteristic of RDD, the diagnosis of purely cutaneous RDD may be complicated by the rare, nonspecific clinical appearance of skin lesions and the broad histopathological differential diagnosis of this disorder. A high level of suspicion of this disease on the part of the clinician or pathologist is often required. We present a case of cutaneous RDD associated with involvement of periodontal tissue.     

Rosai Dorfman syndrome — A rare clinical entity

Sinus histiocytosis with massive lymphadenopathy (also known as Rosai Dorfman syndrome) is a unique disease of unknown etiology with a childhood predilection. It is an uncommon benign condition, often confused with lymphoma. Patients usually present with massive, painless, bilateral cervical lymphadenopathy and clinical course is variable. This condition has been sporadically reported in Indian literature. Here we report a 26-year-old women presenting with a painless bilateral cervical lymphadenopathy. A FNAC from cervical lymph node was compatible with Rosai Dorfman syndrome and confirmed histopathologically.     

A case of nivolumab-induced cervical lymphadenopathy in a patient with gastric cancer

Nivolumab is a monoclonal antibody targeting programmed cell death-1 (PD-1) that has been recently shown to exhibit clinical efficacy in patients with gastric cancer. However, various degrees of immune-related adverse events (irAEs) have been reported. We report the case of a 71-year-old male patient diagnosed with gastric cancer with peritoneal metastases. He was treated with nivolumab as third-line chemotherapy. On the 10^th day after completing seven cycles of nivolumab treatment, he urgently visited the hospital because of mild left cervical lymphadenopathy. We suspected it to be due to inflammation and initiated treatment with levofloxacin hydrate. However, 3 days later, he was admitted to the emergency room due to exacerbation of his lymphadenopathy. A diagnosis of nivolumab-induced lymphadenopathy was made as the antibiotics were ineffective, and the patient was administered prednisolone (PSL) 20 mg. One day after admission, the pain and swelling of the lymph node greatly lessened, and the following day, the pain gradually disappeared; thereafter, the PSL dose was tapered and nivolumab treatment was resumed. The patient again developed cervical lymphadenopathy approximately 4–5 days after nivolumab was reintroduced, which disappeared 1 week later. During each episode of lymphadenopathy, he received a dose of 20 mg of PSL for 4 days, which would be eventually tapered to 10 mg without antibiotics and NSAIDs. After 2 months, cervical lymphadenopathy completely disappeared while 10 mg of PSL was continued, which was also eventually tapered off. To our knowledge, this is the first case report of nivolumab-induced lymphadenopathy in a patient with gastric cancer. This case suggested that we should keep in mind that various irAEs may occur during treatment with immune checkpoint inhibitors. It is necessary to ensure the absence of infection and metastasis before treatment and to promptly administer systemic corticosteroids to address them.     

A role for radiation in the treatment of hairy cell leukemia complicated by massive lymphadenopathy: a case report

A patient with leukemic reticuloendotheliosis is described who two years following splenectomy developed massive retroperitoneal, abdominal, and mediastinal lymphadenopathy. Therapeutic intervention was necessary because the bulky tumor masses produced disabling pain in the back and chest regions. Low-dose radiation to the involved fields produced prompt regression of the adenopathy along with dramatic pain relief. This case suggests that hairy cells may be quite sensitive to radiation, and this therapeutic modality should be considered, especially when local problems are present.     

Angio-immunoblastic lymphadenopathy terminating as Hodgkin's disease.

The clinical course of a 33-year-old man with generalized lymphadenopathy bearing all physical, laboratory and histologic characteristics of "angio-immunoblastic lymphadenopathy with dysproteinemia" (AILD) is described. Therapy was without significant benefit and the patient died 22 months after initial diagnosis. At autopsy in addition to the characteristic cellular polymorphism of AILD, numerous Hodgkin's cells and Sternberg-Reed cells were identified in the lymph nodes and spleen. Pleomorphic cellular infiltrates containing an increased number of immunoblasts and some giant cells were found also in the portal spaces of the liver. The evolution of Hodgkin's disease (H.D.) from AILD suggests that the latter may have represented a reaction to the agent which causes H.D..     

Impressive activity of lenalidomide monotherapy in refractory angioimmunoblastic T‐cell lymphoma: report of a case with long‐term follow‐up

Angioimmunoblastic T‐cell lymphoma (AITL) is characterized by an aggressive clinical course and unfavourable prognosis. Refractory AITL patients have very few treatment options. Lenalidomide has previously been reported to have clinical efficacy in this setting; however, long‐term reports are limited. A 59‐year‐old man was referred to the hospital with fatigue, skin rash, weight loss and generalized lymphadenopathy and was diagnosed with AITL; clinical stage was IV B with bone marrow involvement. The patient had an unsatisfactory response despite three lines of conventional chemotherapy and radiotherapy. The patient received lenalidomide monotherapy (25 mg once daily) on days 1 to 21 of every 28‐day cycle for six cycles, followed by maintenance therapy with six cycles of lenalidomide 15 mg once daily on days 1 to 21 of every 28‐day cycle. A computed tomography scan was assessed before lenalidomide treatment, after the third cycle, at disease restaging 2 months after completion of the induction phase, every 3 months during the maintenance phase and every 6 months during the follow‐up period. At the last evaluation, after a follow‐up of 30 months, the patient maintained a clinical and radiological complete response. The treatment was well tolerated with manageable toxicity. Lenalidomide treatment demonstrated for the first time in the literature impressive and long‐term clinical efficacy in a heavily pretreated chemorefractory AITL patient. Copyright © 2012 John Wiley & Sons, Ltd.