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Subcutaneous calcification following chest wall and breast irradiation by mmo13137


									The British Journal of Radiology, 75 (2002), 279–282   E   2002 The British Institute of Radiology

Case report
Subcutaneous calcification following chest wall and
breast irradiation: a late complication
Departments of 1Radiation Oncology and 2Radiodiagnosis, Royal Devon & Exeter Hospital, Barrack Road,
Exeter, Devon EX2 5DW, UK

    Abstract. Subcutaneous calcification as a complication of chest wall irradiation has only been
    described once before in the literature. Six patients who developed heavy calcification of soft
    tissue following chest wall and breast irradiation are described here, and relevant literature is

   Calcification, a phenomenon often regarded by              supraclavicular regions were treated with two
pathologists as little more than evidence of cell            parallel opposing fields. Follow-up at 1 month
death, is becoming recognized to be important in             showed minimal radiation reaction on the chest
the dynamics of a variety of diseases from which             wall, and this resolved completely over the
millions of people suffer. Calcification as a                 ensuing 2–3 weeks. Since then the patient has
manifestation of late effects of radiation therapy           remained disease free. In February 1988, chest
has been reported only once before, in a patient             radiography showed loss of volume of the left
with carcinoma of the left breast [1]. Radiation             lung with upper zone fibrosis. In addition there
therapy is the most effective and frequently used            were two irregular calcified lesions, one of which
local treatment in breast carcinoma. Late com-               appeared to lie partly outside the rib cage
plications following radiation therapy can be                (Figure 1). However, a skeletal isotope scan had
severe and debilitating in some patients. The                shown no areas of abnormal high activity in the
incidence of late complications is related to many           rib cage or in the region of calcification. Routine
factors including total dose, fraction size, patient         haematological tests and biochemical profile were
age and extent of disease. Pre-existing abnormal-            essentially normal. CT undertaken more recently
ities such as scleroderma are known to result in             showed extensive heterotopic calcification centred
exaggerated radiation responses, with reported               around the left anterior chest wall (Figure 2).
marked fibrosis but not calcification [2]. In the six
cases described here, calcification probably devel-
                                                             Case 2
oped owing to the larger fraction sizes (greater
than 2.0 Gy) and/or the overlap between the                   A 76-year-old woman underwent left simple
glancing and supraclavicular radiotherapy fields              mastectomy in February 1988 for a G2 T2 N0 M0
resulting in delivery of higher doses of radiation
than intended.

Case reports
Case 1
  A 71-year-old woman underwent left Patey
mastectomy in October 1980 for a G2 T2 N1 M0
infiltrating ductal carcinoma of the breast. Post-
operatively she was followed-up with radiation
therapy to the left chest wall and the draining
lymphatics on a telecobalt unit prescribing a
mid-plane dose of 42.5 Gy in 15 fractions over
20 days. A four field technique was used. The
chest wall was irradiated by using two glanc-
ing fields applying a bolus. The axillary and
                                                             Figure 1. Chest radiograph showing two calcified
Received 25 July 2001 and accepted 9 November 2001.          masses in the left upper zone.

The British Journal of Radiology, March 2002                                                               279
                                                                    R Amin, C Hamilton-Wood and D Silver

                                                      normal. The pain subsided and the patient con-
                                                      tinued to remain well until October 1990, when
                                                      she presented following a diagnosis of non-small
                                                      cell carcinoma of the right lung. Chest radiog-
                                                      raphy showed collapse/consolidation of the
                                                      medial basal segments of the right lower lobe.
                                                      In addition there was now a dense area of
                                                      lobulated calcification in the left upper zone.
                                                      Chest CT showed considerable loss of volume of
                                                      the right lower lobe with a right basal effusion.
                                                      There was also calcification in the intercostal
                                                      space and deep to the pectoral muscles. The
Figure 2. CT scan showing heterotopic calcification    underlying lung parenchyma showed some fibrotic
on the left anterior chest wall.                      changes. Despite treatment of her lung primary,
                                                      the patient’s condition continued to deteriorate
infiltrating ductal carcinoma of the left breast.      and she died in July 1990. Autopsy was not
Post-operatively she was offered chest wall and       carried out.
supraclavicular irradiation prescribing a mid-
plane dose of 45.0 Gy in 20 fractions over            Case 4
26 days to the chest wall and an incident dose
of 45.0 Gy in 20 fractions over 26 days to the          A 48-year-old woman presented in January
supraclavicular fossa. Her treatment was under-       1979 with a lump in her left breast. Excision
taken on a telecobalt unit and a bolus was used to    biopsy showed poorly differentiated adenocarci-
treat her chest wall. Follow-up at 1 month showed     noma. The patient underwent simple mastectomy
brisk erythema on her chest wall that resolved        followed by radiation therapy to the chest wall
completely. From the point of view of the breast      and draining lymphatics. She was treated with a
carcinoma, the patient remains disease free.          four field technique on a telecobalt unit and was
However, she has now developed an ovarian             prescribed a dose of 42.5 Gy in 15 fractions over
malignancy. In the course of staging, chest radiog-   20 days. Following this the patient remained well
raphy revealed lobulated areas of calcification in     until March 1981, when she presented with
the left upper zone. In addition there was a right-   hyperaesthesia along the inner aspect of the left
sided pleural effusion, which appeared to be          forearm. The patient demonstrated slight numb-
related to the newly diagnosed ovarian malig-         ness along the C7 distribution. This was not
nancy.                                                associated with weakness of the arm. It was not
                                                      until 3 years later that weakness of the muscles of
                                                      the left hand developed. Over the ensuing 6 years
                                                      there has been very little progress of the weakness
Case 3
                                                      and no sign of recurrence of carcinoma. 1 month
   A 63-year-old woman underwent wide local           ago she presented with a non-productive cough.
excision of a lump from her left breast in            Chest radiography showed no evidence of pul-
November 1974 for a spheroidal cell carcinoma.        monary metastases but there was calcification of
No axillary sampling was undertaken. Post-            soft tissue in the left upper zone extending outside
operatively she was followed-up with radiation        the rib cage.
therapy to her left breast and the draining lym-
phatics. Her breast was treated by two glancing
                                                      Case 5
fields prescribing a mid plane dose of 45.0 Gy in
20 fractions over 26 days. The axilla and supra-        A 57-year-old woman underwent a left simple
clavicular regions were treated by using two          mastectomy in July 1977 for a G1 T2 N0 M0
parallel opposing fields prescribing a mid plane       carcinoma of the left breast. Post-operatively she
dose of 45.0 Gy in 20 fractions over 26 days.         commenced tamoxifen, which was followed by
Treatment was undertaken on a telecobalt unit.        radiation to the chest wall and the draining
Following this the patient remained well until        lymphatics. The patient was treated on a tele-
August 1981, when she developed pain on her left      cobalt unit using a four field technique with
upper anterior chest wall. Chest radiography          glancing fields to the chest wall and parallel
showed some early radiation changes in the left       opposed fields to supraclavicular and axillary
upper zone and in the anterior ends of the left 3rd   regions. She was prescribed a dose of 42.5 Gy in
and 4th ribs. However, a skeletal isotope scan had    15 fractions over 20 days. Bolus was used to treat
shown no abnormal uptake in the region of the         the chest wall. The patient developed a brisk
left 3rd and 4th ribs and the rest of the scan was    radiation reaction that settled over a period of

280                                                            The British Journal of Radiology, March 2002
Case report: Subcutaneous calcification following irradiation

6 weeks. Thereafter she remained well until
October 1983, when she presented with stiffness
of the shoulder. This gradually progressed over
the next 6 months, by which time she had
developed brachial plexopathy. There was no
evidence of recurrence of carcinoma. The patient
then presented in 1997 with symptoms of cough
and pain in the left side of her chest. Chest
radiography had not shown any evidence of
pulmonary or pleural metastases but there was
evidence of radiation induced fractures of the left
3rd and 4th ribs. Once again there was no
evidence of recurrence of carcinoma. The cough
resolved without any specific therapy and pain
was controlled with analgesics. She then remained
well until November 2000, when chest radiog-
raphy showed a calcified mass in the left upper
zone. There was no evidence of recurrence of her
treated carcinoma and the brachial plexopathy                  Figure 3. CT scan showing calcification within a mass
had not progressed.                                            and along the anterior chest wall.

                                                               adriamycin in combination. Cycles were repeated
Case 6
                                                               at 3-weekly intervals. After six cycles there was
   A 37-year-old woman underwent left simple                   good regression of the tumour. In December 1992
mastectomy in September 1972 for an infiltrating                the patient was considered for forequarter ampu-
carcinoma of the left breast. Following this she               tation. In April 1993 she developed a small
remained well until May 1974, when carcinoma                   recurrence in the skin graft. CT showed involve-
recurrence developed in the left axilla. This was              ment of the chest wall and possibly of the apex of
excised and followed by radiation therapy to the               the left lung. Thereafter there was relentless
chest wall and draining lymphatics. The patient                progress of the disease and she died in
was treated on a telecobalt unit. The chest wall               November 1993.
was treated with glancing fields using bolus, and
the axilla and supraclavicular fossa were treated
with two parallel opposing fields. The patient was
prescribed a mid plane dose of 40.0 Gy in 10                      Radiation therapy is the most effective and
fractions over 23 days. She then remained well                 frequently used local treatment in breast carci-
until November 1988, when she presented with                   noma. There are many different techniques for
pain in the neck and left shoulder. Clinical and               delivering radiation. The volume irradiated will
radiological assessment had shown no sign of                   depend on the extent of the breast carcinoma and
recurrent disease. The pain resolved with analge-              the extent of surgery undertaken. For some
sics. In March 1992 she presented again with pain              patients it is sufficient to irradiate the breast or
and swelling over the left shoulder. Clinically                the chest wall alone, whilst in others it is neces-
there was no evidence of recurrence on her chest               sary to irradiate the breast or the chest wall and
wall, but there was a 10.0 cm610.0 cm swelling                 the lymph nodes. In the early 1980s it was
overlying the left shoulder joint posteriorly. This            common practice to irradiate the lymph nodes as
was tethered deeply. Chest radiography had                     routine. Today, chest wall and lymph node
shown peripheral calcification in the left upper                irradiation are usually only given for selected
zone and radiography of the shoulder showed                    patients who have a high risk of recurrence.
erosion and possible fracture of the neck of the                  Radiation therapy to the breast or the chest
scapula. A bone scan showed focally increased                  wall and the nodal areas often presents a technical
activity in the left scapula. Further investigations           problem to match the glancing fields with the
were undertaken with CT and MRI. These                         axillary and supraclavicular fields. Overlap be-
confirmed a large soft tissue mass invading the                 tween these fields will result in underlying tissues
soft tissue in the axilla and the chest wall. There            receiving a larger dose than intended. In all six
was calcification within the mass and along the                 cases presented, the area of dense calcification
anterior end of the rib cage (Figure 3). Biopsy of             appeared to lie in the region where overlap of the
the mass showed spindle cell sarcoma. The                      matching fields could have easily occurred in view
tumour was inoperable so treatment consisted                   of a minor position change between fields. It is
of cyclical chemotherapy using cisplatin and                   generally accepted that fraction sizes significantly

The British Journal of Radiology, March 2002                                                                   281
                                                                       R Amin, C Hamilton-Wood and D Silver

over 2.0 Gy may lead to increased late side             micro-environment may eventually be converted
effects. In breast cancer the total dose required       into calcium hydroxyapatite. Crystal proliferation
to eradicate microscopic disease is 40.0–50.0 Gy        then follows with the extension of calcification
in 15–25 fractions. This dose is increased for          into the extracellular space. Calcification therefore
macroscopic disease or for areas at higher risk of      follows cell death. It is promoted by the presence
recurrence, such as excision margins after breast       of alkaline phosphatase, which is most effective in
conserving surgery. Unwanted side effects of            an alkaline milieu [5]. Radiation leads to vascular
radiation include early acute effects and chronic       damage, thereby causing thickening of the vessel
late effects. Early acute effects occur during or       walls and proliferation of intimal and subintimal
shortly after treatment and are transient. Chronic      cells. Later, circulatory efficiency is compromized
late effects can occur weeks, months or years after     by fibrotic and sclerotic changes of the vessels. It
treatment and tend to persist and get worse.            is possible that hypoxia created by the late effects
   Late complications following radiation therapy       of radiation cause calcification by a cellular mech-
can be severe and debilitating in some patients.        anism as suggested by White et al [6]. Necrotic or
The incidence of late complications is related to       degenerative tissues are likely to be alkaline owing
many factors including total dose, fraction size,       to their low metabolic rate and, hence, reduced
patient age, extent of disease and pre-existing         carbon dioxide production. Conversely, it has been
abnormalities. The main delayed toxicities are          suggested that loss of calcification can indicate
atrophy, telangiectasia, dyspigmentation and,           accelerated growth of malignant tumours [7].
rarely, necrosis of the skin. With modern mega-            Benign conditions of calcification include bleed-
voltage machines the maximum dose lies beneath          ing, infarcts, metabolic disorders or parasites.
the skin and severe late skin changes are unusual,      Calcification of metastases can also be observed
but subcutaneous fibrosis is fairly common.              following radiation [3, 8]. Interestingly, all six
Severe fibrosis in the axilla can obstruct the lym-      cases described here, and that described by Cowie
phatic or venous drainage. Calcification of soft         and Jones [1], had developed dense calcification
tissue following irradiation is an extremely rare       following radiation to left sided breast lesions.
sequela. So far only one case has been reported in      The significance of this will not be known until
the literature [1]. This patient was treated on an      more cases are reported.
orthovoltage unit, whilst the above six patients
were treated on a megavoltage (telecobalt) unit.
The breast and the chest wall were irradiated by        Acknowledgment
tangential fields and the lymph nodes were treated
                                                         We wish to thank Neal Amin for typing the
by parallel opposing fields of equal sizes. Due care
was taken to match the fields, using a gap of
1.0 cm to prevent any overlap of the upper edge
of the beam of the chest wall and breast tangents
and the lower edge of the beam of the anterior
cervico–axillary or supraclavicular fields. How-
ever, a penumbra trimmer was not used in any of         1. Cowie R, Jones R. Subcutaneous calcification as a
                                                           late effect of orthovoltage chest wall irradiation. Clin
the above six patients. All fields were treated at
                                                           Oncol 1999;11:196–7.
each treatment session. Three patients were             2. Robertson JM, Clarke DH, Pevzner MM, et al.
prescribed 42.5 Gy in 15 fractions over 20 days,           Breast conservation therapy. Severe breast fibrosis
two patients were prescribed 45.0 Gy in 20                 after radiation therapy in patients with collagen
fractions over 26 days and one patient was                 vascular disease. Cancer 1991;68:502–8.
prescribed 40.0 Gy in 10 fractions over 23 days.        3. Anderson HC. Calcific lesions: a concept. Arch
                                                           Pathol Lab Med 1983;107:341–8.
   The pathogenesis of the formation of calcium         4. Yoon K, Golub E, Rodon GA. Alkaline phospha-
deposits in the soft tissue remains poorly under-          tase cDNA transfected cells promote calcification
stood. However, pathological calcification can be           and phosphate deposition. Connect Tissue Res 1989;
subdivided into metastatic, occurring in undam-            22:17–25.
aged tissues when extracellular calcium and             5. Halpin S, Kingsley D. Disappearance of cerebral
                                                           calcification as a sign of tumour growth. Neuroradiol
phosphate concentrations are increased, and dys-           1993;14:119–22.
trophic, occurring in injured tissue when extra-        6. White BC, Wiegenstein JG, Winegar B. Brain
cellular calcium and phosphate concentrations are          ischemic anoxia. Mechanism of injury. JAMA 1984;
normal [3]. A cellular mechanism for calcification          251:1586–90.
has been suggested [4]. In the presence of hypoxia,     7. Peretti-Viton P, Margain D, Murayama N, et al.
                                                           Metastases cerebrales. J Neuroradiol 1991;18:161–72.
the equilibrium of extracellular calcium fails and      8. Ricke J, Baum K, Hosten N. Calcified brain meta-
there is an influx of calcium into the cell, resulting      stases from ovarian carcinoma. Neuroradiol 1996;
in calcium phosphate deposition, which in a stable         38:460–1.

282                                                              The British Journal of Radiology, March 2002

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