Calcification of Untreated Mediastinal Hodgkin’s Lymphoma: A Case
Report
*Candice D Rivest, H.B.Sc. (MD Candidate 2010), Faculty of Medicine,
McMaster University
Michael Di Ianni, MD, Department of Radiology, McMaster University
Ehsan Haider, MD, MBBCh, FRCPC, Department of Radiology, McMaster
University Medical Centre
CORRESPONDING AUTHOR EMAIL ADDRESS: candice.rivest@medportal.ca
Abstract
Calcification occasionally occurs in Hodgkin’s lymphoma after therapy due
to tissue necrosis. Rarely, calcification may be detected prior to treatment. This
likely represents a dystrophic process when bulky tumours outgrow their blood
supply. Due to this rare presentation, pre-treatment calcified Hodgkin’s
lymphoma may be mistaken for germ cell tumours on imaging. It is thus
important to include Hodgkin’s lymphoma in the differential of this presentation.
We present such a case of pre-treatment calcification of Hodgkin’s lymphoma in
a young male and discuss the incidence, pathophysiology and imaging findings.
KEYWORDS: Hodgkin’s lymphoma, calcification, pre-treatment, mediastinal,
untreated
Case Presentation
A 24 year old male presented to the Emergency Room complaining of
shortness of breath that was ongoing for three weeks. The patient was using a
budesonide/formoterol inhaler with no relief. His symptoms became worse when
he lied on his right side and back. The patient was otherwise healthy and had no
constitutional symptoms. He had a five year history of smoking and occasional
alcohol use.
On examination, the patient was afebrile with stable vital signs. There
were no auscultatory findings on respiratory examination. There was palpable
right supraclavicular lymphadenopathy. Abdominal and cardiac examinations
were unremarkable.
Laboratory examination revealed a decreased leukocyte count of 3.2 x
109/L with an absolute neutrophil count of 0.8 x 103/mm3. All other laboratory
investigations were within normal range. Chest radiograph showed a soft tissue
density mass involving the anterior mediastinum (Figure 1). Calcifications were
not demonstrated radiographically.
Figure 1: Chest radiograph showing a widened
mediastinum
Computed Tomography (CT) of the chest with intravenous contrast was
performed which confirmed a large homogenous mass with soft tissue
attenuation involving the anterior and middle mediastinum and right hilum. The
mass contained a single, lobulated and coarse calcification measuring 12mm in
diameter (Figure 2a). The mass resulted in marked narrowing of the right main
pulmonary artery and mild mass effect on the right mainstem bronchus (Figure
2b). Bilateral supraclavicular, prevascular and pericardial adenopathy was also
noted. There were no abnormalities seen in the upper abdomen.
Figure 2a: CT chest showing calcification (black
arrow), mediastinal and hilar involvement of the
mass (white arrows)
Figure 2b: CT chest showing narrowing of the right
main pulmonary artery (white arrow)
A needle core biopsy was taken from the right supraclavicular node
suggesting the diagnosis of Hodgkin’s lymphoma of nodular sclerosing type.
Immunohistochemistry for CD15, CD20, CD30 and fascin confirmed the
diagnosis. Bone marrow biopsy was negative.
Background and Epidemiology
Hodgkin’s lymphoma has an annual incidence of 2.8 out of 100,000
persons in the United States1. The World Health Organization (WHO) recognizes
five subtypes of Hodgkin’s Lymphoma: nodular sclerosing, mixed cellularity,
lymphocyte-rich, lymphocyte depleting, and lymphocyte predominate2. The
former four encompass the classical type based on similar histological
morphology which account for 95% of cases with the most common being
nodular sclerosing (65-70%)1. The mean age at diagnosis is 38 years1.
Calcification in lymphoma is rare, occurring 1-5 years after chemotherapy
or radiation therapy with an incidence of 2%3. This process has been shown to
be associated with a good prognosis with 75% of patients being disease free 8
years after therapy3,4. In comparison, calcification before treatment in Hodgkin’s
lymphoma is an even more rare finding, occurring in 0.4% of patients 5-9. NonHodgkin’s Lymphoma has a higher rate of pre treatment calcification at 1%5,10.
Pathophysiology
Even though the physiology of pre-treatment calcification has yet to be
established, two mechanisms have been proposed. The first mechanism is
metastatic in nature resulting from an excessive serum concentration of unstable
calcium ions11. Hypercalcemia can be caused by osteolytic metastases, tumour
secretion of parathyroid hormone related protein, or by tumour production of
calcitrol, which is the most common process occurring in lymphomas12.
However, hypercalcemia in Hodgkin’s lymphoma is very rare with only one case
reported in the literature13. A metastatic process is unlikely to be the cause of
pre-treatment calcification in our patient as his serum calcium concentration was
within normal limits (2.47 mmol/L).
The second potential mechanism is dystrophic calcification that is due to
tissue necrosis. This occurs when excessive calcium enters the mitochondria of
dying cells to form extracellular hydroxyapatite crystals. This process can occur
in bulky tumours that outgrow their blood supply which present with multifocal
areas of calcification6. It has been suggested that the nodular sclerosing type of
Hodgkin’s Lymphoma may be more susceptible to calcification before and after
treatment. In the reported cases of pre-treatment calcified Hodgkin’s
Lymphoma5-9, only one was found not to be of this type, but rather of mixed
cellularity5. Predisposing factors include collagen fibrosis, cellular degeneration,
and necrosis6.
Differentials and Diagnosis
Awareness of this phenomenon is important as the finding of calcification
might otherwise be used to exclude lymphoma from one’s differential diagnosis
of an anterior mediastinal mass. In face, all four of the common anterior
mediastinal masses (thyroid and thymic masses, germ cell tumours, and
lymphoma) may present with calcification, thereby limiting this finding as a
distinguishing feature14.
A mediastinal mass in a young adult will most commonly be a germ cell
tumour or Hodgkin’s lymphoma. Findings on chest radiograph between these two
processes are often indistinguishable, requiring CT for further investigation.
Distinguishing features on CT include inhomogeneity of soft tissue components
in germ cell tumours, including cystic or fatty components, versus relative
homogeneity in Hodgkin’s lymphoma. Secondly, Hodgkin’s lymphoma may
involve any compartment whereas germ cell tumours typically develop in the
anterior mediastinum with posterior displacement of structures6. Therefore, in
order to differentiate between mediastinal masses, a CT scan is essential.
Back to the Case
Upon additional investigations including a CT of the abdomen and
pelvis, a stage of 2A was assigned. A stage of 2A refers to two or more lymph
node regions on the same side of the diaphragm being involved with no “B”
symptoms1. The patient was referred to the Oncology service for therapy and is
currently undergoing chemotherapy.
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