Sections

Presentation

History

The presentation of patients with non-Hodgkin lymphoma is acute or subacute, in contrast to the indolent course that characterizes most lymphomas in adults.

The duration of symptoms before diagnosis is generally 1 month or less, with specific complaints varying according to the predominant sites of involvement.

Bone marrow involvement in non-Hodgkin lymphoma may cause generalized or migratory bone pain, but clinically significant cytopenias are uncommon, with their presence suggesting a diagnosis of acute leukemia.

Symptoms of localized disease

Localized disease can manifest as lymphadenopathy (usually with firmness and no tenderness), tonsillar hypertrophy, or a mass in virtually any location. In children, however, non-Hodgkin lymphoma is primarily an extranodal disease.

Patients with supradiaphragmatic disease (eg, lymphoblastic lymphoma) often report having a nonproductive cough, dyspnea, chest pain, and dysphagia.

Abdominal tumors (usually small noncleaved cell lymphoma [SNCCL] or B-cell large cell lymphoma [LCL]) are associated with abdominal pain, constipation, masses, or ascites. An acute abdomen occasionally is observed and may be mistaken for appendicitis. Rare primary non-Hodgkin lymphoma of the pancreas presents with the clinical picture of pancreatitis.^[46]

Symptoms of large cell lymphomas

Constitutional symptoms are uncommon in non-Hodgkin lymphoma, except in patients with anaplastic large cell lymphoma (LCL). Many of these patients have low-grade fever, malaise, anorexia, and/or weight loss. Because LCLs are biologically disparate, however, these lesions have a varied presentation that may include chest or abdominal complications. In rare cases, an LCL appears as an isolated bone lesion in association with pain, swelling, and a risk of pathologic fracture.

Patients with anaplastic LCLs sometimes present with painful skin lesions, bone lesions, peripheral lymphadenopathy, and hepatosplenomegaly.^{[47, 48]}The painful skin lesions may regress spontaneously. A finding less common than these is testicular, lung, or muscle involvement.

Anaplastic LCLs may also result in an apparent cytokine storm, with fevers, vascular leakage, and pancytopenia.

Symptoms of CNS involvement

Patients occasionally develop symptomatic CNS involvement before diagnosis. Headache, meningismus, cranial nerve palsies, and altered sensorium may be observed. Although CNS involvement is uncommon at the time of diagnosis, patients with non-Hodgkin lymphoma (particularly SNCCL) occasionally present with symptoms suggestive of meningoencephalitis.

Other

Among the less common lymphomas of childhood, primary cutaneous/subcutaneous involvement can be seen (eg, in cutaneous T-cell lymphoma or blastic plasmacytoid dendritic cell hematodermic neoplasm).

Physical Examination

Patients with non-Hodgkin lymphoma generally appear mildly to moderately ill. They occasionally have a low-grade fever. Patients may present with pallor, respiratory distress, pain, and discomfort.

A jaw or orbital mass is present in as many as 10% of patients in industrialized countries, but this finding is particularly common in African patients with endemic Burkitt lymphoma.

Other clinical findings in non-Hodgkin lymphoma include the following:

Cervical or supraclavicular masses or adenopathy is/are firm, fixed, and nontender
Dyspnea or stridor may occur in patients with a mediastinal mass
In patients with superior vena cava syndrome, distended neck veins and plethora may be observed
Decreased breath sounds are secondary to bronchial obstruction or pleural effusion
Thoracic dullness to percussion may be present with pleural effusion.
Abdominal distention or a mass may be present with or without tenderness, rebound tenderness, and/or shifting dullness
Painful skin lesions suggest an anaplastic large cell lymphoma (LCL); the less common forms of cutaneous lymphoma (T-cell, blastic plasmacytoid dendritic) are typically nontender
Obtundation, agitation, and meningismus may be observed in individuals with CNS involvement.
Focal pain or swelling in the extremity may be present in patients with primary bone lymphoma.

Relatively uncommon physical findings include the following:

Nasopharyngeal mass
Parotid enlargement
Nephromegaly
Testicular enlargement

Differential Diagnoses

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Media Gallery

Massive mediastinal T-lymphoblastic lymphoma. Note compression of the left mainstem bronchus and the pulmonary atelectasis.
Non-Hodgkin lymphoma of the terminal ileum. Note the doughnut sign, ie, intraluminal contrast material surrounded by a grossly thickened bowel wall. This appearance is highly suggestive of small noncleaved cell lymphoma (Burkitt type).
Malignant pleural effusion. Non-Hodgkin lymphoma of the terminal ileum was diagnosed; the doughnut sign (ie, intraluminal contrast material surrounded by a grossly thickened bowel wall) was present. A diagnosis of stage 3 Burkitt lymphoma was established by means of pleurocentesis. (The bone marrow was normal.) The patient was treated successfully and never required an abdominal procedure.
Massive left pleural effusion as a complication of an upper anterior mediastinal T-lymphoblastic lymphoma. Note the atelectatic left lung. The diagnosis was established by means of thoracentesis. This patient had presented with bilateral parotid gland enlargement.

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Author

J Martin Johnston, MD Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Hematology/Oncology, The Children's Hospital at Memorial University Medical Center; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, International Society of Paediatric Oncology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

Timothy P Cripe, MD, PhD Professor of Pediatrics, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center; Clinical Director, Musculoskeletal Tumor Program, Co-Medical Director, Office for Clinical and Translational Research, Cincinnati Children's Hospital Medical Center; Director of Pilot and Collaborative Clinical and Translational Studies Core, Center for Clinical and Translational Science and Training, University of Cincinnati College of Medicine

Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Kathleen M Sakamoto, MD, PhD Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Co-Associate Program Director of the Signal Transduction Program Area, Jonsson Comprehensive Cancer Center, California Nanosystems Institute and Molecular Biology Institute, University of California, Los Angeles, David Geffen School of Medicine

Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, International Society for Experimental Hematology, Society for Pediatric Research, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Phase	Drug		Route
Induction	Cyclophosphamide, vincristine, daunorubicin		IV
	Ara-C, methotrexate		IT
	Prednisone		PO
Consolidation	Ara-C		IV or SC
	6-thioguanine		PO
	Methotrexate		IT
	L-asparaginase		IM
	BCNU		IV
Phase	Cycle	Drug	Route
Maintenance^*	1	6-thioguanine	PO
		Cyclophosphamide	IV
	2	Hydroxyurea	PO
		Daunorubicin	IV
	3	Methotrexate	PO
		BCNU	IV
	4	Ara-C	IV or SC
		Vincristine	IV
Source: Children's Cancer Group Ara-C = cytarabine; BCNU = 1,3-bis(2-chloroethyl)-1-nitrosourea, or carmustine; IM = intramuscular; IT = intrathecal; IV = intravenous; PO = oral; SC = subcutaneous ^* A minimum of 5 repeated courses (total duration of therapy >18 mo) are noted. Each course of intrathecal methotrexate (day 0 of each course) consists of 4 cycles of rotating drug pairs that are administered every 2 weeks after blood counts have recovered.

Phases	Drug	Route
Induction	Prednisone, 6-mercaptopurine	PO
	Vincristine, daunorubicin, cyclophosphamide, Ara-C	IV
	L-asparaginase	IM
	Methotrexate	IT
Consolidation	6-mercaptopurine	PO
	Methotrexate with leucovorin rescue	IV
	Methotrexate	IT
Re-induction	Dexamethasone, 6-thioguanine	PO
	Vincristine, doxorubicin, cyclophosphamide, Ara-C	IV
	L-asparaginase	IM
	Methotrexate	IT
Maintenance^†	6-mercaptopurine, methotrexate	PO
Source: Berlin-Frankfurt-Munster Group Ara-C = cytarabine; IT = intrathecal; IV = intravenous; PO = oral; SC = subcutaneous ^* Diagnoses included lymphoblastic lymphoma of the T-cell or precursor B-cell type, immunoblastic T-cell lymphoma, and other peripheral T-cell lymphomas. Of note, patients with Ki-1+ anaplastic large cell lymphomas (LCLs) were not included. ^† Continued until 24 months after diagnosis.

Clinical Group	Subjects, Estimated %	Definition
A	10	All resected stage I or abdominal stage II tumors
B	65	Unresected stage I or II tumor, stage III, tumor, or stage IV tumor with no CNS involvement and < 25% marrow blasts
C	25	CNS involvement or >25% marrow blasts

Drug	Route
Prednisone	PO
Vincristine, cyclophosphamide, doxorubicin	IV
Filgrastim (G-CSF), to enhance neutrophil recovery	SC or IV
G-CSF = granulocyte colony-stimulating factor; IV = intravenous; PO = oral; SC = subcutaneous ^* See Table 3 for the definition of group A. All subjects received 2 cycles.

Phase	Drug		Route
Reduction	Prednisone		PO
	Vincristine, cyclophosphamide		IV
	Methotrexate/hydrocortisone		IT
Phase	Cycles	Drug	Route
Induction	2, starting 7 days after reduction	Prednisone	PO
		Vincristine, methotrexate with leucovorin rescue, cyclophosphamide, doxorubicin	IV
		Methotrexate/hydrocortisone	IT
		Filgrastim (G-CSF)	SC or IV
		Rituximab	IV
Consolidation	2	Methotrexate with leucovorin rescue, Ara-C	IV
		Methotrexate/hydrocortisone, Ara-C/hydrocortisone	IT
		Filgrastim (G-CSF)	SC or IV
		Rituximab	IV
Maintenance**	1	Prednisone	PO
		Vincristine, methotrexate with leucovorin rescue, cyclophosphamide, doxorubicin	IV
		Methotrexate/hydrocortisone	IT
Ara-C = cytarabine; G-CSF = granulocyte colony-stimulating factor; IT = intrathecal; IV = intravenous; PO = oral, SC = subcutaneous ^* See Table 3 for the definition of group B.

Drug	Route
Dexamethasone	PO
Cyclophosphamide	IV
Methotrexate/Ara-C/prednisolone	IT
Ara-C = cytarabine; IT = intrathecal; IV = intravenous; PO = oral.

Pediatric Non-Hodgkin Lymphoma Clinical Presentation

History

Symptoms of localized disease

Symptoms of large cell lymphomas

Symptoms of CNS involvement

Other

Physical Examination

References

Tables

Contributor Information and Disclosures

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