Dr.Venkatesh Kumar, Dr. C. Jayakumar, Dr. Praveena , Dr. Preethi, AIMS, Kochi.
Fourteen years old male child presented with complaints of high grade intermittent fever (mostly in the evenings, not associated with chills and documented weight loss of 5 kgs since 1 month. He also developed two 1×1 cm swelling over his left shin.
H/O Multifocal Papillary Thyroid carcinoma With Lymphnodal Metastases in the father for which he underwent Total Thyroidectomy + Multilevel cervical lymph node dissection and Radioiodine (I 131) therapy.
On examination,vitals were stable.
General examination revealed pallor. Head to foot examination revealed 2 tender erythematous swelling on left shin (1×1 cm in size, round – erythema nodosum).
Systemic examination revealed hepatosplenomegaly.
Differential diagnosis considered at this time point were:
1. Tuberculosis
2. Brucellosis
3. Inflammatory bowel disease- Crohn’s, Ulcerative colitis.
4. Typhoid
5. Hematological malignancies- Leukemia
6. Lymphoproliferative neoplasms
Investigations:
Hemogram: TC- 18.14 ku/ml, N/L/E- 62.4/26.6/5.2%, Hb- 11.8 gm/dl, Plt- 648 ku/ml, ESR- 107 mm/1st hr.
LFT: SGOT/SGPT- 13.3/7.4 IU/L, ALP-126 IU/L, Total Protein-8.3 gm/dl, Albumin- 4 gm/dl, Globulin- 4.27 gm/dl, TB/DB- 0.31/0.13 mg/dl
RFT: Urea- 17.5 mg/dl, Creatinine-0.71 mg/dl
Sodium- 140 mEq/L, Potassium- 4 mEq/L, Phosphorus : 4.3 mg/dl, Calcium : 9.56 mg/dl.
CRP : 84.65 mg/L (increased), Ceruloplasmin : 51.07 mg/dl, LDH : 164.0 U/L
Chest XRay – B/L hilar infiltrates present
Ultrasound Abdomen :Hepatosplenomegaly.
Peripheral smear : Microcytic Hypochromic Anemia , Neutrophilic Leucocytosis and Thrombocytosis.
Stool R/E : WBC- nil, RBC-nil, No parasites
Sputum for GeneXpert ) : negative
MDCT Enterography : Hepatic hemangiomas. Bowel loops appear normal. No ascites. No significant abdominal lymphadenopathy.
CT Chest with contrast – Areas of ill defined centrilobular nodules seen in bilateral posterobasal lung segments, lateral segment of right middle lobe with few other air space opacities scattered in both the lungs.Multiple conglomerate and discrete mediastinal lymph nodes involving almost all the stations – needs further evaluation to rule out possibility of lymphoma.
Stool Culture : Sterile
Bone Marrow Aspiration : Particulate cellular marrow shows trilineage maturation with occasional histiocytes showing hemophagocytosis.
AFB smear from Bone marrow aspirate : Negative.
Bone marrow -Flow cytometry : No definite immunophenotypic evidence of acute leukemia/bone marrow involvement B/T cell non-Hodgkin lymphoma.
AFB culture from Bone marrow: Negative.
Karyotyping : Chromosome analysis from unstimulated cultures revealed a normal male chromosome complement in all cells examined.
There was no evidence of a chromosome abnormality.
Serum Quantiferon TB gold: Negative
IgM Brucella antibody: Negative
ANA-IFA: 3+ ( Mixed cytoplasmic + fine speckled pattern)
WIDAL test (03/09/2024): Negative.
Endoscopic Bronchial Ultrasound was done the pediatric pulmonary team which showed Normal airway with enlarged multiple mediastinal lymphadenopathy.
Transbronchial Needle Aspiration – Rapid On Site Examination showed- (TBNA ROSE) shows ? Reed Sternberg cells.
Whole Body FDG PET CT – Metabolically active enlarged multiple supradiaphragmatic lymphnodes and diffuse metabolically activity in enlarged spleen – ? Neoplastic/ ? Inflammatory/Infective etiology.FDG Avid and Non Avid reticular opacies, Soft tissue nodules and patchy ground glassing in Bilateral lungs. Diffuse metabolic activity in axial and proximal appendicular skeleton – ? Reactive.
For further confirmation of diagnosis – Pediatric surgery consult was sought and was planned for excision biopsy of left supraclavicular lymph node .
Right Supraclavicular Lymph node biopsy done showed lymph node with effaced architecture. A neoplasm arranged in nodular and diffuse pattern. Predominant cells are small lymphocytes admixed with a few eosinophils. Interspersed large cells with vesicular nuclei and basophilic nucleoli are seen – suggestive of Lymphoproliferative neoplasm.
Immunohistochemistry done for categorisation showed :
Large cells are positive for CD30,a few for CD15. These cells show weak PAX-5 positivity and are negative for CD3,CD20 CD23 show residual FDC CD20 positive follicles and CD3 positive cells are seen admixed. Findings are of Classical Hodgkins lymphoma-mixed cellularity.
Impression: CLASSICAL HODGKIN’S LYMPHOMA (MIXED CELLULARITY TYPE)
DISCUSSION:
Hodgkin’s lymphoma is a malignant process involving lympho-reticular system with bimodal age distribution of 15-35 years and after 50 years. Viral agents such as EBV,CMV and HHV-6 have been implicated in the pathogenesis. Pathognomic feature is presence of Reed Sternberg cell- large cell with multiple or multilobulated nucleoli, that arises from germinal centre B cells but typically has lost most B cell gene expression and function. Subtypes are Nodular lymphocyte predominant and classical Hodgkin’s.The latter includes histological subtypes of lymphocyte rich, lymphocyte depleted , mixed celullarity and nodular sclerosis.Clinical manifestations include painless,non tender firm rubbery cervical or supraclavicular lymphadenopathy, hepatosplenomegaly, signs of bone marrow infiltration,etc. B symptoms presence or absence is important in staging.Treatment consists of combined chemotherapy with or without low dose filed radiation therapy. Chemotherpay regimens include- COPP(Cyclophosphamide, Oncovin, Procarbazine and prednisolone) and ABVD ( Adriamycin,Bleomycin, Vincristine, Dacarbazine). Nwere therapies include anti CD20, anti CD30, PDL1 blocking antibodies. Relapses are common in first 3 years and would need management with aggressive chemotherapy or stem cell transplant.