Diagnostic and management challenges in primary cutaneous anaplastic large cell lymphoma with necrosis,inflammation,and surgical intervention:A case report

BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)poses significant diagnostic difficulties due to its similarity in the appearance of skin lesions with chronic inflammatory disorders and other dermatological conditions.This study aims to investigate these challenges by conducting a comprehensive analysis of a case presenting with PC-ALCL,emphasizing the necessity of accurate differentiation for appropriate management.CASE SUMMARY An 89-year-old female patient with diabetes and hypertension presented with arm and abdominal ulcerated mass lesions.Diagnostic procedures included skin biopsies,histopathological assessments,and immunohistochemistry,complemented by advanced imaging techniques to confirm the diagnosis.The patient’s lesions were determined as PC-ALCL,characterized by necrosis,chronic inflammation,and a distinct immunophenotypic profile,including CD30,CD3,CD4,and EBER,CD56,MUM-1,Ki 67-positive in>80%of tumor cells,CD10,but negative for anaplastic lymphoma kinase,CD5,CD20,PAX-5,Bcl-2,Bcl-6,CD8,and CD15.Recurrence was not reported at the 6-month follow-up.CONCLUSION Accurate PC-ALCL differentiation from similar conditions is crucial for effective management and requires a multidisciplinary approach.

Primary cutaneous anaplastic large cell lymphoma with overexpressed Ki-67 transitioning into systemic anaplastic large cell lymphoma:A case report

BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)differs from systemic anaplastic large cell lymphoma(sALCL)in cell biological behavior,clinical features,treatment,and outcome.PC-ALCL has been reported to rarely transition into sALCL,but the underlying mechanism is not clear.Here we report such a case with certain characteristics that shed light on this.CASE SUMMARY Herein,we report a 43-year-old male with symptoms of a skin nodule and histologically confirmed PC-ALCL with high expression of Ki-67.After three months of observation,two skin nodules re-appeared with muscle layer involvement and was histologically confirmed as sALCL.Seventeen months after receiving six cycles of CHOP regimen,the patient had pain in the chest and back,cough,shortness of breath,and night sweats.This was confirmed as relapse of sALCL by immunohistochemistry and several organs,such as the lung were involved as shown by positron emission tomography/computed tomography.After four cycles of DICE plus chidamide regimens followed by auto-hematopoietic stem cell transplantation(ASCT),complete remission(CR)duration was achieved for twelve months while the patient was on maintenance with chidamide(20 mg)pills.CONCLUSION This case had significantly high expression of Ki-67 when diagnosed as PC-ALCL initially and then transitioned into sALCL,which is rare.Auto-ASCT combined with demethylation drugs effectively maintained CR and prolonged progression free survival.

Primary anaplastic lymphoma kinase-positive large B-cell lymphoma of the left bulbar conjunctiva: A case report

BACKGROUND Anaplastic lymphoma kinase(ALK)-positive large B-cell lymphoma(LBCL)is an aggressive and rare variant of diffuse LBCL.Herein,we report an uncommon case of stage IE extranodal ALK-positive LBCL initially originating in the bulbar con-junctiva.CASE SUMMARY A 63-year-old woman presented with a mass in the left bulbar conjunctiva that had persisted for six months,accompanied by swelling and pain that had per-sisted for 3 d.Eye examination revealed an 8 mm slightly elevated pink mass in the lower conjunctival sac of the left eye.Microscopically,the tumor was com-posed of large immunoblastic and plasmablastic large lymphoid cells with scattered anaplastic or multinucleated large cells.Immunophenotypically,the neoplastic cells were positive for ALK,CD10,CD138,Kappa,MUM1,BOB.1,OCT-2,CD4,CD45,EMA,CD79a,CD38,and AE1/AE3,and negative for CD20,PAX5,Lambda,BCL6,CD30 and all other T-cell antigens.The results of gene rearrangement tests showed monoclonal IGH/IGK/IGL and TCRD rearran-gements.Fluorescence in situ hybridization studies did not reveal any BCL2,BCL6 or MYC rearrangements.Furthermore,Epstein-Barr virus was not detected by in situ hybridization in the lesions.Based on the histopathological and imaging examinations,the neoplasm was classified as stage IE ALK-positive LBCL.No further treatments were administered.At the 6,15,and 21 mo postoperative follow-up visits,the patient was in good condition,without obvious discomfort.This case represents the first example of primary extranodal ALK-positive LBCL presenting as a bulbar conjunctival mass,which is extremely rare and shares morphological and immunohistochemical features with a variety of other neo-plasms that can result in misdiagnosis.CONCLUSION Awareness of the condition presented in this case report is necessary for early and accurate diagnosis and appropriate treatment.

Primary pancreatic anaplastic large cell lymphoma, ALK negative: A case report

We present the fourth case of a primary pancreatic anaplastic large cell lymphoma (ALCL), ALK-. An 80-year-old man was admitted to our clinic for further investigation of a fever of unknown origin. He noted anorexia, weight loss and fatigue. His laboratory tests showed anemia and a great elevation of ESR, LDH, and β2 microglobulin. In CT and MRI scan, a soft tissue mass in the pancreas was observed. A repeated endoscopy after his admission revealed an ulcerated mass-like deformity of the duodenal bulb. Explorative laparotomy confirmed a diffuse spread of an unresectable malignant pancreatic mass extending to the adjacent organs. Duodenal and surgical biopsies identified an ALCL of T-cell lineage, ALK-. The patient died in the Intensive Care Unit due to hemodynamic instability.Our case is the first one indicating that primary pancreatic lymphoma should be suspected in a patient with pancreatic mass and elevated serum LDH and β2 microglobulin.

ALK-positive anaplastic large cell lymphoma presenting multiple lymphomatous polyposis: A case report and literature review

BACKGROUND Anaplastic large cell lymphoma(ALCL)is a type of T-cell lymphoma that can be divided into two categories:anaplastic lymphoma kinase-positive(ALK+)and ALK-negative.Gastrointestinal ALK+ALCL is rare.Multiple lymphomatous polyposis(MLP)is thought to be a representative form of gastrointestinal lesion in mantle cell lymphoma,and T-cell lymphomas seldom show this feature.Here,we report the first known case of ALK+ALCL with gastroduodenal involvement to present with MLP.CASE SUMMARY The patient was a 43-year-old man who was complained of a mass in the left inguinal area and was performed open biopsy.ALK+ALCL was diagnosed pathologically.Computed tomography scan demonstrated multiple lymph node lesions in the abdomen-pelvis/inguinal region,and scattered nodular lesions in both lung fields.He did not complain of gastrointestinal symptoms.While,esophagogastroduodenoscopy identified MLP lesions from the antrum of the stomach to the descending portion of the duodenum and mild thickened folds on the corpus of the stomach,and biopsy showed invasion of ALK+ALCL.We treated this patient with six cycles of CHOEP(Cyclophosphamide,Doxorubicin,Vincristine,Etoposide,and Prednisone)chemotherapy.At the conclusion of treatment,there was complete remission.Numerous white scars were found on the stomach,endoscopically consistent with a remission image of lymphoma.The endoscopic features of this case were thought to be similar to those of MCL.CONCLUSION The macroscopic/endoscopic features of gastrointestinal ALK+ALCL may be more similar to those of B-cell lymphomas rather than T-cell lymphomas.

Single Abscess as the First Manifestation of Breast ALK-Positive Anaplastic Large Cell Lymphoma in Pregnancy Without Breast Implants:A Case Report

Primary lymphoma involving the breast accounts for only 0.04-0.5%of malignant breast tumors,constituting 1-2%of all non-Hodgkin lymphomas(NHL).Here,we report a case of breast ALK-positive ALCL arising in a 21-year-old woman in pregnancy with single abscess as the first clinical manifestation.

Anaplastic lymphoma kinase-negative anaplastic large cell lymphoma masquerading as Behcet’s disease: A case report and review of literature

BACKGROUND Anaplastic large cell lymphoma(ALCL)is a CD30-positive T cell lymphoma,a rare type of non-Hodgkin lymphoma.The current World Health Organization classification system divides ALCLs into anaplastic lymphoma kinase(ALK)-positive and ALK-negative groups.ALCL rarely presents in the gastrointestinal tract.CASE SUMMARY A 54-year-old male was admitted to the department of gastroenterology for abdominal pain.He presented with lower abdominal pain,diarrhea and recurrent oral and penile ulcers.He was misdiagnosed with Behcet's disease and treated with prednisone.But after one month,he was hospitalized in another hospital for reexamination.This time,the lesion on the penis was biopsied for histological examination.The final pathological diagnosis was ALCL,ALKnegative.The patient was treated with cyclophosphamide,doxorubicin,vincristine,prednisolone chemotherapy.However,he died within one month.CONCLUSION Gastrointestinal ALCL needs to be considered in the differential diagnosis to avoid delaying treatment.Repeated biopsy is the most important for early diagnosis and treatment.

Kawasaki disease, <i>Mycoplasma pneumoniae</i>infection and anaplastic large cell lymphoma: An uncommon association

Kawasaki disease (KD) is an acute febrile systemic vasculitis occurring predominantly in young children less than 5 years of age. Although imperfectly known, the aetiopathogenesis of KD would be secondary to immunological abnormalities that could constitute a favourable terrain for neoplasms. We report on a case in a 2-year-old girl who presented clinical manifestations compatible with Kawasaki disease complicated by coronary aneurysm. Aetiopathological investigations revealed M. pneumoniae infection as specific IgM were present in the serum (Elisa). The patient was initially treated by intravenous immunoglobulins (IVIG) and aspirin to anti-inflammatory dose. Following a few days of desquamation, resolution of the symptomatology occurred. Four weeks later she developed disseminated tumorous syndrome. Lymph node biopsy revealed massive infiltration by large cells lymphomatous proliferation. Histologic and immunophenotypic findings were characteristic of ALK-1+ anaplastic large cell lymphoma. Four weeks later, the patient died from a severe nosocomial infection complicated by septic shock. Our observation is the first cases describing the association between anaplastic large cell lymphoma, KD and M. pneumoniae. Immunologic disorder due to KD and M. pneumoniae infection may play probably a central role for malignancy.

ALK-positive anaplastic large cell lymphoma of the thoracic spine occurring in pregnancy: A case report

BACKGROUND Anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin’s lymphoma (NHL). ALCL is rare as a bone lesion and in pregnancy. CASE SUMMARY We present the first case of anaplastic lymphoma kinase (ALK)+ ALCL of the thoracic spine during pregnancy. A 25-year-old pregnant woman was presented to us at 24 wk’ gestation with severe back pain and weakness in the left lower limb. Imaging examination showed lesions at T10 and T11. She underwent posterior pedicle screw fixation and vertebroplasty. Pathological examination showed ALK+ ALCL. The patient chose to have therapeutic abortion after surgery and received chemotherapy in the hematology department. She now remains disease free with no neurological deficit after 30 mo’ follow-up. CONCLUSION ALK+ ALCL with the thoracic spine involvement is uncommon, especially in pregnancy. Many symptoms can be misunderstood during pregnancy;therefore, when a pregnant patient has persistent back pain or lower limb neurological symptoms, imaging examinations should be performed.

CD30-Positive Anaplastic Large Cell Lymphoma with Abundant Neutrophils (Report of a Case)

ObjectiveTo report a rare case of ALCL (Anaplastic Large Cell Lymphoma) with abundant neutrophils and necrosis and to analyse the histomorphologic subtypes and immunohistologic characteristics of ALCL. MethodsA biopsy of a painless tumor on a 26 year old male′s neck was taken for morphologic and immunohistochemical analyse. ResultsJudging from the morphologic feature of ALCL,the prognosis of the patient is good. ConclusionIt is necessary to do immunohistochemical staining in diagnosing an ALCL since p80 NPM/ALK or ALK is the best antibody to distinguish ALCL from other lymphomas.

Primary cutaneous anaplastic large cell lymphoma with subsequent leg involvement

Primary cutaneous anaplastic large cell lymphoma(CALCL)is regarded as an indolent type of cutaneous T-cell lymphoma.However,a few recent publications revealed that C-ALCL patients with initial leg involvement had significantly worse survival than those without initial leg involvement.Herein,we report a case of C-ALCL with subsequent leg involvement,which led to death after chemoradiation therapy.A 75 years old Japanese man presented with multiple erythematous nodules in his left arm and the side of his left chest.Histopathological and immunohistochemical studies led to the diagnosis of primary C-ALCL.At the initial diagnosis,no leg lesion was found.One year after the initial diagnosis,C-ALCL appeared in his right lower thigh and left hip.Radiation therapy,low-dose etoposide and CHOP therapy were performed;however,the patient died of malignant lymphoma 4 years after the initial diagnosis.We speculated that the occurrence of subsequent leg involvement may also be indicative of a worse prognosis,as in the case with initial leg involvement in C-ALCL.Therefore,we propose that C-ALCL patients with initial or subsequentleg involvement should be classified as a distinct clinicopathological variant of C-ALCL("leg-type"involvement)and that they may require intense therapy.

Long Lasting Efficiency of Monthly Vinblastine in a Case of Relapsed Anaplastic Large Cell Lymphoma

Nearly 40% of children with Anaplastic Large cell lymphomas will relapse after a first-line strategy with short-pulse chemotherapy and reach a second remission in 30% to 60% with second line therapies including maintenance treatment with vinblastine or allogeneic hematopoietic stem-cell transplantation. The authors report a heavily pretreated case in second relapse who was maintained in third remission for 8 years with monthly vinblastine. He relapsed 16 weeks after discontinuation. This case demonstrates that monthly treatment with vinblastine may be sufficient to maintain a minimal disease. Oral compounds are now available and should be discussed in such situations.

Brentuximab Vedotin Monotherapy and Combined with Low Dose Donor Lymphocyte Infusion to Control Minimal Residual Disease and Sustain Clinical Remission in a Child with Relapsed Anaplastic Large Cell Lymphoma

Minimal residual disease (MRD) appears to have a strong negative predictive value for disease recurrence in children with anaplastic large cell lymphoma (ALCL). Brentuximab vedotin (BV) can be a therapeutic option for MRD-positive patients to achieve molecular remission and to decrease risk of subsequent relapse. We here report a 4-year-old child with ALCL progression during relapse treatment who received BV as a bridging therapy before haploidentical hematopoietic stem-cell transplantation, and as a maintenance therapy post-transplant alone or combined with simultaneous low dose donor-lymphocyte infusions. MRD monitoring showed a complete molecular response and reflected both BV efficiency and graft-versus-lymphoma effect.

Primary bone anaplastic lymphoma kinase positive anaplastic largecell lymphoma: A case report and review of the literature

BACKGROUND Primary bone lymphoma(PBL)is an uncommon extranodal disease that represents approximately 1%-3%of lymphomas.Anaplastic lymphoma kinase(ALK)positive anaplastic large-cell lymphoma(ALCL)is an extremely rare type of PBL.The aim of this report is describe the symptoms,diagnosis,and treatment of primary bone ALK-positive ALCL.CASE SUMMARY A 66-year-old man presented to our hospital with neck and shoulder pain and intermittent fever that lasted for 1 mo.After extensive evaluation,positron emission tomography-computed tomography(CT)examination showed multiple osteolytic bone lesions without other sites lesions.CT-guided biopsy of the T10 vertebral body was performed,and the pathology results showed that neoplastic cells were positive for ALK-1,CD30,and CD3.A diagnosis of primary bone ALK positive ALCL was ultimately made.The patient was in partial response after four cycle soft cyclophosphamide,doxorubicin,vincristine,and prednisone chemotherapy,and we planned to repeat the biopsy and radiological examination after completion of the fifth cycle of therapy.CONCLUSION Primary bone ALK positive ALCL is a rare disease and physicians should keep in mind that ALCL can present with isolated osseous involvement without nodal involvement,and lymphoma should be considered in the differential diagnosis of primary bone lesions.

Diffuse large B-cell lymphoma successfully treated with amplified natural killer therapy alone: A case report

BACKGROUND The prognosis of patients with advanced diffuse large B-cell lymphoma(DLBCL)is poor,with a 5-year survival rate of approximately 50%.The mainstay of treatment is multidrug combination chemotherapy,which has been associated with serious side effects.Amplified natural killer(ANK)cell therapy amplifies and activates natural killer(NK)cells to attack only malignant tumors.As ANK cells attack programmed death ligand 1(PD-L1)-positive tumor cells,ANK therapy is considered effective against adult T-cell lymphoma and malignant lymphoma.CASE SUMMARY Herein,we report a case of an older patient with advanced DLBCL who was successfully treated with ANK immunotherapy.A 91-year-old female visited our hospital with sudden swelling of the right axillary lymph node in April 2022.The patient was diagnosed with stage II disease,given the absence of splenic involvement or contralateral lymphadenopathy.ANK therapy was administered.Six rounds of lymphocyte sampling were performed on July 28,2022.To reduce the occurrence of side effects,the six samples were diluted by half to obtain 12 samples.Cultured NK cells were administered twice weekly.The treatment efficacy was evaluated by performing computed tomography and serological tests every 1 or 2 mo.The treatment suppressed lesion growth,and the antitumor effect persisted for several months.The patient experienced mild side effects.PD-L1 immunostaining was positive,indicating that the treatment was highly effective.CONCLUSION ANK therapy can be used as a first-line treatment for malignant lymphoma;the PD-L1 positivity rate can predict treatment efficacy.

Pathological complete response to neoadjuvant alectinib in unresectable anaplastic lymphoma kinase positive non-small cell lung cancer:A case report

BACKGROUND The development of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitors(TKIs)has remarkably improved the prognosis of patients with ALK-positive advanced non-small cell lung cancer(NSCLC).Alectinib,the second-generation ALK-TKI,has been approved as first-line treatment for advanced or metastatic NSCLC patients with ALK rearrangement.Neoadjuvant therapy can achieve tumor downstaging and eradicate occult lesions in patients with potentially resectable disease.Whether neoadjuvant alectinib can be a conversion therapy in ALK-positive advanced NSCLC patients remains unclear.CASE SUMMARY A 41-year-old man was pathologically diagnosed with locally advanced ALKpositive stage IIIB NSCLC.Alectinib was prescribed to induce tumor downstaging and facilitate the subsequent surgical resection.The tumor was successfully downstaged and pathological complete response was achieved.Left upper lobectomy with mediastinal lymphadenectomy was performed after tumor downstaging.The patient has continued to receive alectinib as adjuvant therapy during postoperative follow-up with a recurrence-free survival of 29 mo as of writing this report.CONCLUSION This case sheds light on the feasibility and safety of alectinib as a neoadjuvant treatment for stage IIIB NSCLC patients with ALK rearrangement.Its efficacy needs to be validated in prospective clinical trials.

Acute leukemic phase of anaplastic lymphoma kinase-anaplastic large cell lymphoma: A case report and review of the literature

BACKGROUND Anaplastic large cell lymphoma(ALCL)is a rare and heterogeneous malignant tumor,which is classi
ed as anaplastic lymphoma kinase(ALK)positive ALCL and ALK-ALCL.Many patients are diagnosed with ALCL at the stage of bone marrow involvement.However,ALCL patients with clinical manifestations consistent with acute leukemia are relatively rare.CASE SUMMARY In this report,the patient did not receive appropriate diagnosis and treatment despite a two-year history of lymph node enlargement.Hereafter,she was admitted for B symptoms and was diagnosed as ALK-ALCL by lymph node biopsy.Then,the disease progressed to leukemia without any treatment after 2 mo.The proportion of lymphoma cells in bone marrow was as high as 96%,and the proportion of peripheral blood was 84%.She also had clinical manifestations similar to acute leukemia.After completion of chemotherapy,she developed granulocytopenia and fever and died from septicemia.CONCLUSION ALCL with leukemic presentation is a late manifestation of lymphoma with low chemotherapy tolerance and poor prognosis.

Dihydroartemisinin enhances cell apoptosis in diffuse large B cell lymphoma by inhibiting the STAT3 activity

Background:Dihydroartemisinin(DHA)is reported to be a potential anticancer agent,and the mechanisms underlying the effects of DHA on diffuse large B cell lymphoma however are still obscure.This study aimed to assess the antitumor effect of DHA on diffuse large B cell lymphoma cells and to determine the potential underlying mechanisms of DHA-induced cell apoptosis.Methods:Here,the Cell Counting Kit 8 assay was conducted to study cell proliferation.We performed Annexin V-FITC/propidium iodide staining,real-time polymerase chain reaction,and western blot analysis to analyze cell apoptosis and potential molecular mechanisms.Results:The results showed that DHA substantially suppressed cell proliferation and induced cell apoptosis in vitro in a time-and concentration-dependent fashion.Moreover,STAT3 activity could be inhibited after stimulation with DHA.Conclusion:These results imply that the underlying anti-tumoral effect of DHA may increase apoptosis in diffuse large B cell lymphoma cells via the STAT3 signaling pathway.In addition,DHA might be an effective drug for diffuse large B cell lymphoma therapy.

Effect of T-regulatory cells and interleukin-35, interleukin-10, and transforming growth factor-beta on diffuse large B-cell lymphoma

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is an aggressive non-Hodgkin lymphoma that affects B lymphocytes.It can develop in the lymph nodes and can be localized or generalized.Despite DLBCL being considered potentially curable,little research has been conducted on the relationship between the body's immune response and DLBCL.AIM To study the expression and significance of T-regulatory cells(Tregs)interleukin(IL)-35,IL-10,and transforming growth factor-beta(TGF-β)in DLBCL.METHODS Data from 82 patients with DLBCL who were initially admitted to The First Affiliated Hospital of Ningbo University(Zhejiang Province,China)between January 2017 and June 2022 and treated with standard first-line regimens were reviewed.Three patients were lost to follow-up;thus,79 patients were included in the statistical analysis and then divided into three groups according to the evaluation of clinical efficacy:Incipient(new-onset and treatment-naïve),effectively treated,and relapsed-refractory.Thirty healthy individuals were included in the control group.The expression of peripheral blood T lymphocytes and their associated factors IL-35,IL-10,and TGF-βin the four groups were observed.RESULTS In contrast to the successfully treated and normal control groups,both the incipient and relapse-refractory groups exhibited greater proportions of CD4-positive(+)Tregs(P<0.05),whereas the proportion of CD8+Tregs did not differ substantially between the groups.Serum levels of IL-35 and IL-10 in the incipient and relapsed-refractory groups were higher than those in the effectively treated and normal control groups(P<0.05).There was no statistically significant distinction in the expression level of TGF-βbetween the groups(P>0.05).The correlation between IL-35 and IL-10 concentrations was significantly positive,with a correlation coefficient of 0.531(P<0.05).The correlation between IL-35 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.375(P<0.05).The correlation between IL-10 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.185(P<0.05).The expression concentrations of IL-35,IL-10 and TGF-βwere apparently and positively correlated(P<0.05).CONCLUSION Tregs IL-35,and IL-10 may be closely associated with the occurrence and development of DLBCL and the detection of related indices may be helpful in the analysis of disease prognosis.

Anaplastic Large Cell Lymphoma, ALK-Negative Presenting in the Rectum: A Case Report and Review of the Literature

ALK-negative anaplastic large cell lymphoma (ALCL, ALK-) is a CD30+ T-cell neoplasm composed of large lymphoid cells with abundant cytoplasm and pleomorphic nuclei that lacks expression of ALK protein. We describe a case of ALCL, ALK-with primary involvement of the rectum in a 37 year old man, where the original diagnosis was established based on a colonoscopic biopsy. T-cell lymphomas are rare in the colorectal area and besides ALCL, their differential diagnosis includes enteropathic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, NK/T cell lymphoma, or NK-cell enteropathy. In addition, syncytial variant of classical Hodgkin lymphoma or a pleomorphic CD30-positive diffuse large B-cell lymphoma should also be ruled out. We discuss pitfalls of the differential diagnosis and review the literature of anaplastic large cell lymphoma in the gastrointestinal tract. Correct diagnosis of ALCL in the colon is important to avoid a colorectal surgery for an assumed adenocarcinoma, and to open the possibility for lymphoma-directed chemotherapy.