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 is often 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
Background
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.
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 the normal range. Chest radiographs showed a soft
tissue density mass involving the right hilum and anterior mediastinum.
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. The mass resulted in marked narrowing of the right main pulmonary
artery and mild mass effect on the right mainstem bronchus. Bilateral
supraclavicular, prevascular and pericardial adenopathy was also noted. There
were no abnormalities seen in the upper abdomen.
Figure 2: CT chest showing calcification (black
arrow), mediastinal and hilar involvement of the
mass (white arrows)
Figure 3: 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. Upon additional investigations
including a CT of the abdomen and pelvis, a stage of 2A was assigned. The
patient was referred to the Oncology service for therapy and is currently
undergoing chemotherapy.
Discussion
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 patients5-9. NonHodgkin’s Lymphoma has a higher rate of pre treatment calcification at 1%5,10.
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, tumor
secretion of parathyroid hormone related protein, or by tumor 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 tumors 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.
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 tumors, 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 tumor or Hodgkin’s lymphoma. The density, homogeneity,
location, and degree of mass effect can help to differentiate between these two
lesions6.
References
[1] SEER stat fact sheets [Internet]. Bethesda: National Cancer Institute; c19752006 [cited 2009 Feb 2]. Available from:http://seer.cancer.gov/statfacts/html
/hodg.html.
[2] Fritz A., ed., et al. International classification of diseases for oncology. 4th ed.
Geneva: WHO; 2000.
[3] Brereton HD, Johnson RE. Calcification in mediastinal lymph nodes after
radiation therapy of Hodgkin’s disease. Radiology. 1974;112:705-707.
[4] Bertrand M, Chen JT, Libshitz HI. Lymph node calcification in hodgkin’s
disease after chemotherapy. AJR. 1977;129:1108-1110.
[5] Apter S, Avider A, Gayer G, Portnoy O, Zissin R, Hertz M. Calcification in
lymphoma occurring before therapy: ct features and clinical correlation. AJR.
2002;178:935-938.
[6] Shinn SS, Bran comb BV, Ho KJ. Massive mediastinal hodgkin’s disease with
calcification masquerading teratocarcinoma: differentiation by computed
tomography. CT: The Journal of Computed Tomography. 1985;9:321-327.
[7] Panicked DM, Hartly MP, Scicutella CJ, Carsky ED. Calcification in untreated
mediastinal lymphoma. Radiology. 1988;166:735-736.
[8] Cattleman B, Towne VM, eds. Massachusetts General Hospital: case record
no. 42242. NEJM. 1956;254:1139-1141.
[9] Wycoco D, Ravel B. An unusual presentation of mediastinal hodgkin’s
lymphoma on computed tomography. Journal of Computed Tomography.
1983;7:187-188.
[10] Apter s, Saks N, Hardan I, Amitai M, Langevitz P, Livneh A. Calcification in
untreated non-hodgkin’s mediastinal lymphoma. Southern Medical Journal.
1998;91: 212-213.
[11] Devita VT. Cancer: principles and practice of oncology. Philadelphia:
Lippincott Williams & Wilkins; 2005.
[12] Stewart AF. Hypercalcemia associated with cancer. NEJM. 2005;352:373379.
[13] Korek-Amorosa J, Scheinman HZ, Clemett AR, Amoroso LF, McKenna PJ.
Hypercalcemia and extensive lymph-node calcification in a patient with
hodgkin’s disease prior to therapy. BJR. 1974;47:905-907.
[14] Collins J, Stern EJ. Chest Radiology: The Essentials. Philadelphia: Walters
Kluwer Health/Lippincott Williams & Wilkins; 2008.