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Since the discovery of radiation by Madame Curie, there have been isolated reports of diseases caused by radiation exposure. It was not until the atomic bomb blasts over Hiroshima and Nagasaki that the world witnessed the full horror of intense radiation exposure. Harnessed by radiation oncologists, radiation has become an effective and important weapon in the armamenterium of today's oncologist.


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Biologic effects dependent upon the following: Dose rate
Rapidly dividing cells more susceptible
Single dose of external radiation administered to whole body is more lethal than regional doses with shielding
Cells in G2 and mitotic phase more susceptible
Hyperbaric oxygen enhances the toxic effect of free radicals generated by ionizing radiation
Cellular mechanisms

Overt necrosis at >10 Gy
No effect at <0.5 Gy

Subcellular damage primarily with DNA damage

Acute effects DNA protein cross links
Increased expression of c-fos, c-jun, and c-myc
Induction of TNF-alpha, superoxide dismutase
Free radical generation
Activation of p53
Fibrosis Induction of IL-1, TNF-alpha, IL-4, PDGF, BFGF, Transforming growth factor-beta

Latent period may be 20 years or more which may be secondary to induced genetic instability

Atom bomb survivors hhade all leukemias except CLL
Increased cancers in breast, thyroid, GI tract, and urinary tract


Effects of electromagnetic radiation from a cellular telephone on epidermal Merkel cells.

Irmak MK, Oztas E, Yagmurca M, Fadillioglu E, Bakir B.

Department of Histology and Embryology,Gulhane Military Medical Academy, Ankara; Departments of Histology and Embryology, and Physiology, Faculty of Medicine, Inonu University, Malatya; and Department of Public Health, Gulhane Military Medical Academy, Ankara, Turkey.

J Cutan Pathol 2003 Feb;30(2):135-138 Abstract quote

The number of reports on the effects induced by electromagnetic radiation (EMR) from cellular telephones in various cellular systems is still increasing.

Until now, no satisfactory mechanism has been proposed to explain the biological effects of this radiation except a role suggested for mast cells. Merkel cells may also play a role in the mechanisms of biological effects of EMR. This study was undertaken to investigate the influence of EMR from a cellular telephone (900 MHz) on Merkel cells in rats. A group of rats was exposed to a cellular telephone in speech position for 30 min. Another group of rats was sham-exposed under the same environmental conditions for 30 min. Exposure led to significantly higher exocytotic activity in Merkel cells compared with the sham exposure group.

This finding may indicate the possible role of Merkel cells in the pathophysiology of the effects of EMR.


Induction of p53 expression in skin by radiotherapy and UV radiation: a randomized study.

Ponten F, Lindman H, Bostrom A, Berne B, Bergh J.

Department of Genetics and Pathology, University Hospital, Uppsala, Sweden. Fredrik

J Natl Cancer Inst 2001 Jan 17;93(2):128-33 Abstract quote

BACKGROUND: p53 protein plays an important role in the response to DNA damage, and radiotherapy can cause radiation dermatitis. p53 and p21 levels increase in vitro when DNA is damaged by UVA, UVB, or gamma-radiation. To determine whether this response occurs in human skin and predicts the level of radiation dermatitis, we investigated levels of p53 and p21 in skin exposed to different types of radiation as part of a randomized study of women with breast cancer to evaluate topical steroid or emollient cream treatments for radiation dermatitis of their irradiated breast.

METHODS: After surgery but before receiving tangential 5-mV photo-beam radiotherapy (2 Gy and 54 Gy) to the affected breast parenchyma, multiple areas on the backs of 50 women were irradiated with UVA and other areas were irradiated with UVB. Skin biopsy samples were taken from areas of normal unirradiated skin and all irradiated areas, and p53 and p21 were detected immunohistochemically. All statistical tests are two-sided.

RESULTS: In skin irradiated with UVA or UVB, medians of 4.4% (range = 0%-40.5%) or 45.5% (range = 5.3%-74.6%) p53-positive keratinocytes, respectively, were observed. Radiotherapy produced medians of 31.0% (range = 0%-79.3%) p53-immunoreactive cells after 2 Gy of radiation and 83.2% (range = 37.6%-95.2%) after 54 Gy of radiation. Despite large interindividual differences in p53 response, comparable increases in epidermal p53 response were independent of the type of radiation. A correlation between p53 and p21 was also evident (r(s) =.78). In breast skin, there was no association between the p53 response and the degree of erythema (a measure of radiation dermatitis) and no statistically significant difference between treatment arms and p21/p53 responses.

CONCLUSIONS: Individual responses to radiation-induced DNA damage varied widely and may be independent of the type of radiation. The epidermal p53 response does not predict the degree of radiation dermatitis.


General Adapted from Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders. 1999.
Acute Radiation Syndrome  
Subclinical <200 Mild nausea and vomiting
Lymphocytes <1500/mm3
100% survival
Hematopoietic 200-600 Intermittent nause and vomiting
Petechiae, hemorrhage
Maximum neutrophil and platelet depression in 2 wks
Lymphocytes <1000/mm3
May require bone marrow transplant
Gastrointestinal 600-1000 Nausea and vomiting, diarrhea
Hemorrhage and infection in 1-3 wks
Severe neutrophil and platelet depression
Lymphocytes <500/mm3
Shock and death in 10-14 days even with replacement therapy
Central nervous system >1000 Intractable nausea and vomiting
Confusion, somnolence, convulsions
Coma in 15 min-3 hr
Lymphocytes absent
Death in 14-36 hours
Delayed Radiation Injury  
Blood vessels
Subintimal fibrosis and luminal narrowing
Constrictive pericarditis
Myocardial ischemia and fibrosis
Intra-alveolar and interstitial fibrosis
Kidneys and urinary bladder
Delayed peritubular fibrosis
Vascular damage
Glomerular hyalinization
GI tract
Strictures and obstruction
Ovary and testis
Atrophy and fibrosis
Eyes and central nervous system
Transverse myelitis



Acute radiation colitis in patients treated with short-term preoperative radiotherapy for rectal cancer.

Leupin N, Curschmann J, Kranzbuhler H, Maurer CA, Laissue JA, Mazzucchelli L.

Institute of Pathology and the Departments of Visceral Surgery and Radiation Oncology, Inselspital, University of Bern, Bern, Switzerland.

Am J Surg Pathol 2002 Apr;26(4):498-504 Abstract quote

The histopathologic features of acute radiation-induced colitis in humans have been described in occasional, >20-year-old studies, but they have not been analyzed in detail.

We characterize such findings in 34 patients with rectal cancer who underwent surgery a few days after preoperative irradiation with 25 Gy given over 5-7 days, and we compare the results to the histopathologic features detected in 18 patients treated by a conventional preoperative irradiation protocol consisting of 45 Gy during 5 weeks followed by surgery after a time interval of at least 3 weeks. Short-term preoperative irradiation therapy generally induced severe mucosal inflammation characterized by increased cellularity of the lamina propria, prominent eosinophilic infiltrates, crypt disarray, surface and crypt epithelial damage, nuclear abnormalities, and presence of apoptotic bodies in the crypt epithelium. These histopathologic features were absent or detected only occasionally in the patient group treated according to the long-term preoperative irradiation protocol. Despite acute severe inflammation, none of the patients treated by short-term irradiation developed perioperative complications. These observations indicate that acute radiation colitis may remain clinically silent and resolve spontaneously within a few weeks after irradiation.

Given the widening acceptance of short-term preoperative irradiation protocols for rectal cancer, pathologists should be aware of the rather characteristic histologic findings of acute radiation colitis and avoid unnecessary concern of clinicians. The differential diagnosis includes infectious colitis, collagenous and ischemic colitis, nonsteroidal anti-inflammatory drug-associated colitis, and chronic idiopathic inflammatory bowel disease.


Postirradiation Pseudosclerodermatous Panniculitis

Loreto Carrasco, M.D.; Carmen Moreno, M.D.; Maria Antonia Pastor, M.D.; Maria José Izquierdo, M.D; Carmen Fariña, M.D.; Lucia Martín, M.D.; Omar P. Sangüeza, M.D.; Luis Requena, M.D.

From the Departments of Dermatology (L.C.,A.P.,J.I., C.F.,L.M.,L.R.) and Pathology (C.M.), Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain, and Departments of Dermatology and Pathology (O.P.S.), Wake Forest University, Winston Salem, North Carolina.

Am J Dermatopathol 2001;23:283-287 Abstract quote

Pseudosclerodermatous panniculitis is an unusual variant of panniculitis that results as a complication of megavoltage radiotherapy. Four women developed this unusual entity on the anterior chest and abdominal skin after receiving megavoltage therapy for either breast carcinoma or painful bone metastases from breast carcinoma.

Histopathologically, the epidermis and dermis of the involved area showed little or no evidence of radiodermatitis. The main findings were confined to the subcutaneous tissue and consisted of thickened, sclerotic septa composed of both thick and thin collagen bundles, and a lobular panniculitis characterized by lipophagic granulomas and scattered lymphocytes and plasma cells. Additionally, one of the cases showed markedly dilated vascular spaces with the appearance of lymphatics in the upper part of the dermis.

Pseudosclerodermatous panniculitis after irradiation is an unusual cutaneous complication of megavoltage radiotherapy that should be distinguished from subcutaneous metastatic disease, cellulitis, or connective tissue diseases involving the subcutaneous fat. The differential diagnosis can be established on the basis of the characteristic histopathologic features of postirradiation pseudosclerodermatous panniculitis.

Post-radiotherapy vascular proliferations in mammary skin: a clinicopathologic study of 11 cases.

Department of Pathology, Stanford University Medical Center, CA 94305, USA.

J Am Acad Dermatol. 2007 Jul;57(1):126-33. Abstract quote

BACKGROUND: Post-radiotherapy atypical vascular lesions (AVL) in mammary skin show significant clinical and histopathologic overlap with well-differentiated angiosarcoma (AS) and pose a considerable diagnostic and managerial challenge when encountered.

OBJECTIVE: We review Stanford's experience with diagnosing AVL and formulate a clinicopathologic approach to these lesions.

METHODS: We performed a clinicopathologic study on 11 cases that were initially diagnosed as AVL and examined whether there are specific clinical or histopathologic features that delineate AVLs from well-differentiated AS.

RESULTS: Clinically, all patients were women with a mean age of 68.1 years, had a history of infiltrating breast carcinoma, and were treated by excision with postoperative radiation therapy. All lesions were located in mammary skin within the prior radiation field. The clinical presentation included erythema, telangiectasias, papules, plaques, and nodules. All patients were diagnosed with AVL on initial biopsy. Six patients showed no recurrence or progression of disease following incomplete excision with no further therapy (3/6) or re-excision with negative margins (3/6). The remaining 5 patients were shown to have AS in the re-excision specimen. The patients diagnosed with AS were older and had a shorter interval from radiation as compared to those who did not experience an adverse outcome. Histologically, all initial biopsy specimens were transected and were characterized by complex, anastomosing vascular proliferations with dilated spaces. Each case was morphologically evaluated according to the AVL criteria of Fineberg and Rosen. Three cases met all of the criteria for AVL, and these patients showed no progression of disease. The remaining cases met most but not all diagnostic criteria for AVL and showed some features of AS, but fell short of a definitive diagnosis of AS, including the 5 cases that were subsequently diagnosed as angiosarcoma.

LIMITATIONS: This retrospective study utilized a small number of cases from a single consultation service; therefore, some inherent selection bias may exist.

CONCLUSION: We could not identify unequivocal clinical or histologic criteria that allows for a sharp separation between AVL and AS. Dermatologists and pathologists need to be aware of the overlap between AVL and well-differentiated AS and all patients who receive a diagnosis of AVL should undergo complete excision with close clinical follow-up and biopsy of any new lesions.
Radiation-Associated Cutaneous Atypical Vascular Lesions and Angiosarcoma: Clinicopathologic Analysis of 42 Cases.

Brenn T, Fletcher CD.

From the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Am J Surg Pathol. 2005 Aug;29(8):983-996. Abstract quote  

Cutaneous angiosarcoma is a rare but well-recognized complication after radiation therapy. Atypical post-radiation vascular lesions (AVLs) with a benign course have been described recently, but few cases with limited follow-up have been studied so far.

A total of 42 cases diagnosed as either radiation-associated cutaneous vascular lesions or angiosarcoma were retrieved from departmental and consultation files from 1995 to 2003. Hematoxylin and eosin-stained sections and clinical as well as follow-up data were evaluated. All patients were female with a median age of 59 years (range, 36-90 years).

Presentation ranged from small erythematous/violaceous papules or nodules to large plaques with discoloration located on the chest wall (35), abdomen (2), shoulder, groin, flank, axilla, and lower leg (1 each). Reasons for radiation included breast carcinoma (35 cases) and a variety of other lesions (mainly malignant disease). Size range was 0.1 to 20 cm. Angiosarcomas presented as larger lesions (median, 7.5 cm) compared with AVLs (median, 0.5 cm).

The time interval from radiation was significantly shorter for the development of AVL (median, 3.5 years) compared with cutaneous angiosarcoma (median, 6 years). Histologic evaluation revealed 26 lesions meeting criteria for angiosarcoma, ranging from morphologically low-grade to high-grade; 16 cases were classified as AVLs. These were fairly well-circumscribed lesions confined within superficial to mid dermis and composed of complex anastomosing and focally dilated vascular spaces. Some showed prominent hyperchromatic endothelial cells, while others were characterized by areas with a dissecting growth pattern within dermal collagen. Endothelial multilayering was absent.

Clinical follow-up, available for 36 patients (range, 2-84 months; median, 17 months), revealed 4 patients who died of disease, 4 patients had systemic metastasis, and 12 patients with local recurrence. All patients with systemic relapse had an initial diagnosis of angiosarcoma. One patient with an AVL had a recurrence at the same site, 3 patients developed additional new lesions, and 1 patient developed multiple small papules on the chest wall, which progressed from an AVL to angiosarcoma.

This study outlines the morphologic spectrum of radiation-associated cutaneous AVLs. No adverse outcome has been observed so far in this more benign subset of cases, but longer-term follow-up is necessary.
Radiation recall dermatitis, panniculitis, and myositis following cyclophosphamide therapy: histopathologic findings of a patient affected by multiple myeloma.

Borroni G, Vassallo C, Brazzelli V, Martinoli S, Ardigo M, Alessandrino PE, Borroni RG, Franchini P.

Department of Dermatology, University of Pavia, Policlinico S. Matteo-IRCCS, Pavia, Italy
Am J Dermatopathol. 2004 Jun;26(3):213-6. Abstract quote

Radiation recall dermatitis is one of the skin sequelae that may affect oncology patients. It occurs in a previously irradiated field, when subsequent chemotherapy is given. The eruption may be elicited by chemotherapy, even several months after radiotherapy. Its mechanism is poorly understood, and the histopathologic findings have received, to date, only sketchy descriptions. A 55-year-old male affected by multiple myeloma received radiation therapy both on his left coxofemoral area, and lumbar region (D11-L1). After cyclophosphamide administration, he developed 2 well defined square-shaped, infiltrated erythematoviolaceous plaques in the prior irradiated fields.

Histopathologic findings revealed a diffusely fibrosclerosing process, involving deep dermis, hypodermis, as well as the underlying muscle, while sparing the epidermis and superficial-mid dermis. Histopathology was indistinguishable from deep radio-dermatitis, panniculitis, and myositis.

This is the first case providing clear evidence of the causative role of cyclophosphamide in inducing a cutaneous and subcutaneous radiation recall reaction.
Subacute radiation dermatitis.

Hivnor CM, Seykora JT, Junkins-Hopkins J, Kantor J, Margolis D, Nousari CH, Naik N, Van Voorhees AS.

Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA.
Am J Dermatopathol. 2004 Jun;26(3):210-2. Abstract quote  

Delayed effects of accidental cutaneous radiation exposure: fifteen years of follow-up after the Chernobyl accident.

Steinert M, Weiss M, Gottlober P, Belyi D, Gergel O, Bebeshko V, Nadejina N, Galstian I, Wagemaker G, Fliedner TM, Peter RU.

Hospital and Clinic for Vascular Surgery and Dermatology, Ulm-Blaustein, Germany.
J Am Acad Dermatol. 2003 Sep;49(3):417-23. Abstract quote  

BACKGROUND: During the Chernobyl accident in 1986, 237 individuals were identified as having the most severe exposure to ionizing radiation. In the period between 1998 and 2000, 99 long term survivors out of this group were reassessed for radiation-induced cutaneous lesions.

OBJECTIVE: To identify sequelae of accidental cutaneous irradiation.

METHODS: Detailed dermatologic examinations, including biopsies of suspicious cutaneous lesions for histopathologic examination and 20 MHz sonography, were performed in all patients.

RESULTS: Twenty-two of the 99 patients displayed radiation-induced cutaneous lesions. Epidermal atrophy, telangiectases, and pigment alterations were present in all these individuals. Keratotic lesions were found in 14 patients. Cutaneous fibrosis was documented in 8 individuals by the use of 20 MHz sonography, while a radiation ulcer was found in 5. In one patient, two basal cell carcinomas were found.

CONCLUSION: The life-long follow-up of irradiated persons is of great importance in order to identify cutaneous neoplasms at an early treatable stage.
Benign Vascular Proliferations in Irradiated Skin

Luis Requena, M.D.; Heinz Kutzner, M.D.; Thomas Mentzel, M.D.; Rafael Durán, M.D.; José Luis Rodríguez-Peralto, M.D.

From the Department of Dermatology (L.R.), Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain; Dermatohistopathologisches Gemeinschaftslabor (H.K., T.M.), Friedrichshafen, Germany; the Department of Pathology (R.D.), Hospital de Elda, Alicante, and the Department of Pathology (J.L.R.-P.), Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.


Am J Surg Pathol 2002;26:328-337 Abstract quote

Several types of cutaneous vascular proliferations have been described in areas of irradiated skin, including both benign lesions, such as benign lymphangiomatous papules, atypical vascular lesions, or benign lymphangioendothelioma, and malignant neoplasms such as high-grade angiosarcomas.

This report describes the clinicopathologic features of 15 cases of different types of benign cutaneous vascular proliferations arisen within irradiated skin. All patients were female ranging in age from 33 to 72 years, and they had received postoperative external radiotherapy for treatment of breast carcinoma (14 cases) or ovarian carcinoma (one case). In those cases in which the latency interval period between radiotherapy and the development of the vascular lesion was known from the clinical records, the latency interval period elapsed between radiotherapy and diagnosis of the vascular lesion ranged from 3 to 20 years. The most common clinical presentation of the cutaneous lesions consisted of papules, small vesicles, or erythematous plaques on the irradiated field.

Histopathologically, most lesions consisted of irregular dilated vascular spaces, with a branching and anastomosing pattern, thin walls, and lymphatic appearance involving the superficial dermis. A discontinuous single layer of endothelial cells with flattened nuclei lined these vascular channels, and numerous small stromal papillary formations also lined by endothelial cells projected into the lumina of the dilated lymphatic vessels. These cases were classified as benign lymphangiomatous papules or plaques. Two cases showed different histopathologic findings because they consisted of poorly circumscribed and focally infiltrating irregular jagged vascular spaces involving the entire dermis and lined by inconspicuous endothelial cells. In some areas these irregular slit-like vascular spaces dissected collagen bundles of the dermis. These cases were classified as atypical vascular proliferations mimicking benign lymphangioendothelioma or patch-stage Kaposi's sarcoma. All cases showed similar immunohistochemical findings and the endothelial cells lining the vascular spaces expressed immunoreactivity for CD31, but they stained only focally positive for CD34 or were negative for this marker. Immunohistochemical investigations for -smooth muscle actin failed to demonstrate a complete peripheral ring of actin-positive pericytes in most of the neoformed vascular structures.

This immunohistochemical profile also supported the lymphatic nature of these vascular proliferations developed in irradiated skin. Although some of these lesions may mimic histopathologically patch-stage Kaposi's sarcoma or well-differentiated angiosarcoma, the follow-up of the patients of this series demonstrated that the vascular proliferations arisen in irradiated skin invariably showed a benign biologic behavior.

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Commonly Used Terms

Becquerel-Measurement of the decay of radioisotopes (Bq=1 disintegration per second)

Curie-Measurement of the decay of radioisotopes (Ci=3.7 x 10*10 disintegrations per second)

Gray (Gy)-Dose of radiation that will produce absorption of 1 joule of energy per kilogram of tissue. 1 Gy=100 rad

Ionizing radiation-Radiation with short wavelengths and high frequency ionize biologic targets and eject electrons (x-rays, gamma rays, cosmic rays).

Non-ionizing radiation- Electromagnetic radiation with long wavelengths and low frequencies (electricity, radio waves, and microwaves).

Particulate radiation-Type of particles emitted (alpha, beta, protons, neutrons, mesons, or deutrons).

Rad-Dose of radiation that will produce absorption of 100 ergs of energy per gram of tissue

Rem-Dose of radiation that causes a biologic effect equivalent to 1 rad of x-rays or gamma rays.

Roentgen-Unit of charge produced by x-rays or gamma rays that ionize a specific volume of air

Sievert (Sv)-Dose of radiation that causes a biologic effect equivalent ot 1 Gy or x-rays or gamma rays. 1Sv=100 rem.

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Last Updated July 11, 2007

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