A 21-year-old female with abdominal lymphadenopathy with ascites

Presenter

Dr. Sharup Chandra Poddar

Resident, phase-B

Haematology

Bsmmu

Particulars-

• Name- Munmun nahar
• Age- 21y
• Sex-Female
• Religion- Islam
• Occupation- House wife
• Address-

Presentations-

• Abdominal pain for 3 months
• Vomiting for 3 months
• Abdominal fullness for 1 months

No History of-

• Bleeding
• Profuse sweating
• Blood vomiting
• Melaena

• She is normotensive, non diabetic
• No significant past medical history
• No H/O blood transfusion

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General examination-

• Appearance : ill looking
• Body built: below average ( chachectic )
• Anaemia : mild
• Jaundice : absent
• Oedema : present
• Bony tenderness: absent
• Lymphadenopathy: absent

• Pulse : 76b/min
• Bp : 90/60 mmhg
• Temp : 98.6
• Others : normal

Systemic examinations-

Abdomen

• Ascities present
• There are multiple intra abdominal lymphadenopathy
• No organomegaly
• Other systemic examination reveals –right sided pleural effusion

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Salient features-

• Mrs. Munmun nahar , 21year, female has been presented with H/O abdominal pain with occasional vomiting for 3 months and abdominal fullness for last 1months. On query she gave h/o of significant weight loss in this period o illness.
• No H/O of hematemesis or melaena.
• No H/O blood components transfusion.

• O/E: She is mildly anaemic
• Non icteric
• Lymhadenopathy - absent
• Bony tenderness - absent
• Vitals are within normal limit.

• There are multiple intra abdominal lymphadenopathy and ascites .
• Features of right sided pleural effusion.
• No organomegaly.
• Other systemic examinations are normal.

*Diagnosis ??

• Lymphoma
• Intra abdominal malignancy
• Disseminated TB

• CT scan of abdomen :
• Long segment symmetrical bowel thickening in volving jejunam
• Extensive intra abdominal lymphadenopathy
• Gross ascites
• Right sided mild pleural effuse
• USG of W/A :
• Long segment bowel thickening involving left lumber region
• Huge ascites

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• Endoscopy of upper GIT:
• The bulb is dilated and contain bile mixed food.
• Post bulbar area shows multiple irregular nodular lesion causing narrowing of lumen.
• Colonoscopy :
• Normal

• USG guided FNAC from abdominal lymphnode:
• NHL - High grade
• Endoscopic biopsy from 2^nd part of duodenum:
• Lymphoproliferative disorder

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Problem lists:

• 1.what may the diagnosis ?
• 2.what investigations can be done to establish the diagnosis?
• 3.what will be the treatment options?

• Plan :
• BMS with trephine biopsy
• ICH –pending
• PET scan

Marginal zone lymphomas (MZLs)

Extranodal MZL (EMZL) - 70%

Splenic marzinzl zone lymphoma (SMZL)- 20%

Nodal MZL (NMZL)

• Marginal zone lymphomas are indolent diseases.
• Overall survival rates are very good, but patients tend to relapse, several times.
• The concept of treatment sequencing is therefore important and necessary to preserve adequate organ function and to avoid excessive toxicity, with the final goal of achieving long survival times.

Clinical case�

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• A 65-year-old man with a 6-month history of dyspepsia received a diagnosis of histologically documented Helicobacter pylori (HP)–positive gastric MALT lymphoma, appearing as a small, ulcerated lesion of the antrum, in the context of global erythema of the gastric mucosa. No signs of active bleeding were detected. The patient was taking acetylsalicylic acid because of a history of transient ischemic attack. He was also taking valsartan and alfuzosin. His peripheral blood counts were normal, and only a subclinical iron deficiency, without anemia, was identified.

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• Disease staging was accomplished by (1) a total-body computed tomography (CT) scan, which showed no enlarged lymph nodes (either perigastric or distant), with slight thickening of the gastric walls appreciated; (2) endoscopy with ultrasonography to document the involvement of the muscularis propria (stage I; T2 N0 M0); and (3) bone marrow biopsy, which was negative for disease infiltration. He was prescribed a proton pump inhibitor and antibiotics, and his disease status was reevaluated 2 months after treatment. The ulceration had completely resolved, but random gastric biopsies documented persistent disease. He was then referred for gastric radiation therapy.

Treatment sequencing in EMZL

• Initial treatment choices in gastric MALT lymphoma
• Gastric MALT lymphoma is localized to the stomach and to its tributary nodes most of the time.
• Thorough locoregional staging is achieved by endoscopy with ultrasonography, and it is important to rule out the presence of HP.
• If histopathology is negative, then a stool antigen test or urea breath test is recommended.

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Antibiotic therapy

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• Indication :

H. Pylori positive gastric MALT lymphoma.

• Tripple therapy :

PPI with

Clarithromycin,

with amoxicillin or metronidazole

• Duration : 10 to 14 days.
• Monitoring :

By urea breath test and stool Ag test -6 weeks after eradication therapy

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• Response assessment : repeated endoscopy with biopsy.
• In endoscopic remission but persistent in histology, wait at least 12 months before starting a new line of treatment, unless the patient is symptomatic.
• In case of failure to achieve a meaningful response, a subsequent treatment with ISRT can be considered.
• In persistent HP positivity- second-line, non–cross-resistant antibiotics.

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Radiation therapy�

ISRT is preferred:

• In localized disease after failure of antibiotic therapy
• HP⁻ localized disease (Perigastric nodes)
• Doses : 24 to 30 Gy

is effective in local disease without significant toxicities.

Rituximab�

Second-line treatment: in

• Failure of antibiotic therapy
• Contraindications to ISRT.
• Dose : 375 mg/m² in each week - 4 weeks.

as a single agent for gastric and extragastric MALT lymphomas.

Surgery�

• The role is controversial as gastric MALT lymphoma is generally multifocal, requiring an extensive (total or subtotal) gastrectomy.
• Gastrectomy is considered : first-line intervention in
• Life-threatening hemorrhage
• Gastric perforation
• Or pyloric stenosis. 

Initial treatment choices in nongastric MALT lymphomas

Surgery�

• An initial surgical approach always necessary for diagnosis
• 1^st line treatment of localized EMZL –
• Lung
• Breast
• Thyroid
• Colon and small bowel.

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Radiation therapy�

1^st line therapy :

• Occular
• Orbital
• Lacrimal & skin lesion

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Rituximab�

• Two phase 2 trials describe the action of rituximab monotherapy in extragastric MALT lymphomas, regardless of stage. As stated, both trials included patients with gastric and nongastric MALT: skin, salivary glands, lungs, and orbits were the most represented sites.
• Single-agent rituximab has also shown efficacy in treatment of cutaneous MZL, particularly in cases with multiple and noncontiguous lesions.

Treatment sequencing in SMZL�

• Treatment is indicated in symptomatic patients with SMZL: with massive splenomegaly causing
• Pain
• Early satiety
• Cytopenia.
• Asymptomatic patients : watch and wait

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• Autoimmune manifestations: such as autoimmune hemolytic anemia or immune thrombocytopenia - Single-agent rituximab.
• Concomitant hepatitis C virus (HCV) infection - antiviral therapy.
•   Rituximab and splenectomy are the recognized first-line treatment options in symptomatic patients.
• Chemoimmunotherapy is an option in case of first-line treatment failure

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Splenectomy

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Indication:

Massive and symptomatic splenomegaly

Peripheral cytopenias.

• It rapidly corrects anemia, thrombocytopenia and neutropenia
•   Does not influence marrow infiltration or blood lymphocytosis.
• Disease dissemination to distant lymph nodes or other parenchymas
• Cytopenias are secondary to massive bone marrow infiltration and are not believed to be correctable by splenectomy alone.

Rituximab�

• Rituximab used as a single agent or combined with chemotherapy is highly effective in this subgroup of patients and is preferred in comparison with splenectomy by some clinicians.
• Single-agent rituximab (375 mg/m² weekly for 4-8 weeks) produces rapid responses, with an ORR of 88% to 100%, CR in nearly 45% to 90% of cases, and a 10-year PFS that may exceed 60%.  It also remains active in cases with disease relapse.

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Chemoimmunotherapy

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• Chemoimmunotherapy regimens are based on rituximab combined with alkylating agents (cyclophosphamide or bendamustine), anthracyclines, or fludarabine.
• Indicated in –

Disseminated disease at presentation with clinical symptoms

Failure first-line therapy

or relapsed disease .

Treatment sequencing in NMZL

• Guidelines recommend that NMZL be treated as any other indolent non-Hodgkin lymphoma with lymph node involvement, according to the principles applied in follicular lymphoma.

Rituximab and radiotherapy�

• In patients with limited-stage disease (stage I or contiguous stage II) ISRT

or rituximab monotherapy.

• Single-agent rituximab is also a valuable first-line option in cases of noncontiguous stage II disease; chemoimmunotherapy is a suitable alternative.

Chemoimmunotherapy:

• Chemoimmunotherapy: is indicated in-
• Symptomatic disease (high tumor burden)
• Advanced-stage disease.
• Failure radiotherapy or rituximab
• Disease progression
• Options
• R+benda
• R+fluda
• R-CHOP/R-CVP.

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Autologous stem cell transplantation�

• Immunomodulators, targeted agents, and new drugs under development
• Systemic approaches with targeted agents, used either as single agents or in combination with immunotherapy, represent a step forward in the optimization of treatment of patients for whom conventional immunochemotherapy is unsuitable and in cases of relapsed or refractory disease.⁴⁸  Enrollment of patients in clinical trials exploring new agents is always desirable when standardized treatment strategies are unavailable. A complete survey of agents being explored in clinical trials is beyond the scope of this article. We provide a review of the existing results with agents we usually apply in patients who experience multiple relapses and meet treatment requirements (Table 4). It is important to note that most of these agents are not formally approved worldwide, as data are generated from subgroup analyses or derived from monocentric experiences.

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• Radioimmunotherapy
• The most significant experience with single-agent ⁹⁰Y-ibritumomab tiuxetan (⁹⁰Y-IT) radioimmunotherapy in relapsed or refractory EMZL. 
• In a study high response rates were reported (90%), with (77%) patients achieving a CR.

• Ibrutinib:

For relapde and refractory disease

Linalodomide with or without rituximab

PI3K inhibitors�

• Highly promising for : relapsed or refractory MZLs.
• Idelalisib, duvelisib, copanlisib, parsaclisib and umbralisib.
• Objective response : 47% to 78%, CR :only7% to 33%
• Toxicity : infections, inflammatory adverse events or metabolic alterations.

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Conclusions�

• MZLs are indolent diseases with long survival rates but a high tendency to relapse over time.
• Extranodal disease is frequently confined to a single organ or site, even in cases with recurrence.
• SMZL, if asymptomatic, may be followed up without treatment for years.
• NMZL is often disseminated at presentation and requires treatment if advanced-stage disease is accompanied by high tumor burden.
• Sequential application of various treatments is the key to success in the treatment of MZL.
• On the one hand, this strategy is necessary to preserve adequate organ function and avoid excess toxicity, as systemic treatment is limited to advanced symptomatic or recurrent disease. On the other hand, this approach increases survival rates.
• New drugs and targeted agents offer treatment opportunities in highly pretreated individuals and in particular categories of patients, often limiting the need for repeated application of cytotoxic drugs.

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