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Lichenoid (Interface)Tissue Reaction Pattern

Psoriasiform Reaction Pattern

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Lichen planus-like lesions

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Cutaneous lesion in graft-versus host disease

Cutaneous infection and infestations

Histopathological patterns in cutaneous infections

1: Bacterial, Rickettsial and Chlamydial infection

2 : Spirochetal Infection

3 : Mycoses and algal infections

4 : Protozoal Infections

5 : Helminth Infections

6 : Viral Infections

Cutaneous lesion associated
with AIDS

Prognostic parameters of melanoma

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Neurotropic melanoma

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Anatomy and Histology of the Normal Lung and Airways

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Anatomical Distribution of Pulmonary Disease

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Radiation dermatitis:

The changes in the skin are divided into: (i) Early changes (acute radiodermatitis) ; (ii) chronic changes (chronic radiodermatitis) (iii) An intermediate subacute stage.

Clinical presentation:

Early radiation dermatitis:

- Erythema in the week following irradiation

- Epilation and hyperpigmentation.

Subacute radiation dermatitis:

-Occurs weeks to months after exposure to radiation.

Subacute radiation dermatitis: a histologic imitator of acute cutaneous graft-versus-host disease.J Am Acad Dermatol. 1989 Feb;20(2 Pt 1):236-41.

The histopathologic changes of radiation dermatitis have been classified either as early effects (necrotic keratinocytes, fibrin thrombi, and hemorrhage) or as late effects (vacuolar changes at the dermal-epidermal junction, atypical radiation fibroblasts, and fibrosis). Two patients, one exposed to radiation therapeutically and one accidentally, are described. Skin biopsy specimens showed an interface dermatitis characterized by numerous dyskeratotic epidermal cells with lymphocytes in close apposition (satellite cell necrosis); that is, the epidermal changes were similar to those in acute graft-versus-host disease. Because recipients of bone marrow transplants frequently receive total body irradiation as part of their preparatory regimen, the ability of radiation to cause persistent epidermal changes similar to those in acute graft-versus-host disease could complicate the interpretation of posttransplant skin biopsy specimens.

Subacute radiation dermatitis from fluoroscopy during coronary artery stenting: evidence for cytotoxic lymphocyte mediated apoptosis.J Am Acad Dermatol. 1998 Feb;38(2 Pt 2):333-6.

A patient with fluoroscopy-induced subacute radiation dermatitis is described. Her biopsy specimen showed vacuolar change and necrotic keratinocytes with lymphocytes in direct apposition, or "satellitosis". Lymphocytes in the dermis and infiltrating the epidermis were predominantly CD8+ and a number of the lymphocytes stained for TIA-1, a cytotoxic granule protein in T-cells and natural killer cells, that appears to be involved in the induction of apoptosis. Our findings suggest cytotoxic lymphocyte mediated apoptosis is involved in the pathogenesis of subacute radiation dermatitis.

Late radiation change:

- Progresses slowly - Occurs many months or years after initial exposure

- Atleast 1000 rads are required to produce chronic radiodermatitis.

Microscopic changes:

Early changes:  

Vacuolization of epidermal nuclei and cytoplasm ; degenerate keratinocytes ; hyperpigmentaion of the basal layer ; Blood vessels are dilated lined by swollen endothelial cells ; Edema of the dermis ; Extravasation of red blood cells ; Fibrin thrombi within blood vessels.

Subacute radiation dermatitis:

Lichenoid tissue reaction (interface dermatitis) - basal vacuolar damage ; apoptotic keratinocytes.  Lymphocytes in the superficial perivascular location in the dermis and also in the epidermis close to apoptotic keratinocytes -"satellitosis" ;  Fibrinopurulents crust on the epidermal surface.

Late stage:

Atrophic epidermis ; loss of normal rete ridge patters ; focal basal vacuolar change ; Sometimes hyperkeratosis ; Dyskeratotic cells are often present ; 

Changes in the dermis - Swollen hyalinized collagen showing irregular eosinophilic staining ; Atypical stellate cells with large nuclei containing clumped chromatin -(Radiation Fibroblasts) ; Telangiectatic vessels in the upper dermis lined by swollen endothelial cells ;  Some arterioles and venules show hyaline change in the wall &narrowing of the lumen ; Loss of dermal appendage - (pilosebaceous structures are absent ; atrophy of eccrine sweat glands) ; Arrector pilli muscles are present ;

Rare features - ulceration ; secondary infection ; inflammation and dysplastic epidermal changes.

Neoplastic lesions: 

A few patients develop squamous and basal cell carcinoma (after about 15 years or more after irradiation). Basal cell carcinomas are more common following irradiation to the head and neck region. Sometimes the tumours that develop in post irradiated skin are more aggressive and there is a higher risk of metastasis.

Cutaneous vascular proliferations:

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.

- 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 . Presentation range  from small erythematous/violaceous papules or nodules to large plaques with discoloration located on the chest wall ,abdomen  , shoulder, groin, flank, axilla, and lower leg.  These are fairly well-circumscribed lesions confined within superficial to mid dermis and composed of complex anastomosing and focally dilated vascular spaces. Some show prominent hyperchromatic endothelial cells, while others are characterized by areas with a dissecting growth pattern within dermal collagen. Endothelial multilayering are usually absent. Although vascular proliferations in irradiated skin may mimic angiosarcoma morphologically, the large majority of these lesions show a benign clinical outcome.

Postirradiation Pseudosclerodermatous Panniculitis:

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.

Histopathologically, the epidermis and dermis of the involved area show little or no evidence of radiodermatitis. The main findings are confined to the subcutaneous tissue and consist 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.

Other non-neoplastic lesions may occur: 

Acne, infectious diseases, dyskeratosis, Grover's disease, sub-cutaneous pustulosis, cutaneous lichen, morphea, autoimmune bullous dermatosis, subacute cutaneous lupus erythematosus.

Environmental Pathology - Radiation : click here

Whole-Body Irradiation: click here

Localized Radiation Injury Associated with Radiotherapy: click here

Radiation and Cancer: click here

                           

Fluoroscopy-induced chronic radiation skin injury: a disease perhaps often overlooked.Arch Dermatol. 2007 May;143(5):637-40.

BACKGROUND: Fluoroscopy-induced chronic radiation dermatitis (FICRD) resulting from prolonged exposure to ionizing radiation during interventional procedures has been documented in the radiology and cardiology literature. However, the phenomenon has been rarely reported in the dermatologic literature. Since patients with FICRD often see a dermatologist or a primary care physician to treat their injuries, the diagnosis of FICRD is perhaps often overlooked. OBSERVATIONS: A 62-year-old man with type 2 diabetes mellitus and severe coronary artery disease was seen with a 2-year history of a pruritic, tender, telangiectatic patch lesion over his left scapula. Over the next 2 years, the lesion became indurated and eventually ulcerated. A skin biopsy specimen demonstrated changes consistent with a chronic radiation dermatitis. The patient was unaware of radiation exposure, but persistent questioning from his dermatologists revealed that he had undergone multiple fluoroscopy-guided cardiac procedures. This was confirmed by a review of his medical records. Conclusion The diagnosis of FICRD should be considered for any patient who is seen with an acquired vascular lesion, a morphealike lesion, or an unexplained ulcer localized over the scapula, the back, or lateral trunk below the axilla.

Post-radiotherapy vascular proliferations in mammary skin: a clinicopathologic study of 11 cases.J Am Acad Dermatol. 2007 Jul;57(1):126-33.

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.

Vascular proliferations of the skin after radiation therapy for breast cancer: clinicopathologic analysis of a series in favor of a benign process: a study from the French Sarcoma Group.Cancer. 2007 Apr 15;109(8):1584-98.

BACKGROUND: Cutaneous vascular proliferations that occur in the field of prior radiotherapy include angiosarcoma and small, cutaneous lesions with a pseudosarcomatous pattern that previously were reported as atypical vascular lesions or benign lymphangiomatous papules. METHODS: The objective of this study was to investigate the clinicopathologic features and outcomes of 56 radiation-induced vascular proliferations that occurred in 36 patients who received previous treatment for breast carcinoma. Data from all patients were retrieved from the files of the French Sarcoma Group. Immunostaining with D2.40 antibody was performed in 24 lesions. RESULTS: All patients (median age, 52 years) had received external radiotherapy. Small papules developed within the field of prior radiotherapy (median latency interval, 66 months). Microscopically, the lesions were relatively well circumscribed, and they were located mostly in the superficial/middermis. They were composed of dilated or irregular-jagged vascular channels that were lined by a single layer of bland endothelial cells, and they demonstrated either a predominately lymphangioendothelioma-like or lymphangioma/lymphangioma circumscriptum-like growth pattern. Micropapillary tufts were common findings. Ten lesions showed additional cytologic and/or architectural atypia. Twenty of 24 lesions showed D2.40 positivity. Follow-up information was available for 31 patients (median follow-up, 48 months): Five women developed new cutaneous lesions, and 1 woman had spontaneous regression of her lesions. None of the patients developed cutaneous angiosarcoma. Five patients were lost to follow-up. CONCLUSIONS: Although vascular proliferations in irradiated skin may mimic angiosarcoma morphologically, the large majority of these lesions showed a benign clinical outcome. Despite relatively limited follow-up, the current results indicate the benign nature of these vascular proliferations.

Radiation-associated cutaneous atypical vascular lesions and angiosarcoma: clinicopathologic analysis of 42 cases.Am J Surg Pathol. 2005 Aug;29(8):983-96.

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.Am J Dermatopathol. 2004 Jun;26(3):213-6.

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.

Radiation-induced skin reactions (except malignant tumors).Bull Cancer. 2003 Apr;90(4) :319-25.

The aim of this work, synthesized from personal case reports and a review of literature is to describe cutaneous complications of radiation therapy (except radiation-induced cancers): known and frequent such as radiation dermatitis or less frequent, beginning or strictly limited on irradiated skin areas: acne, infectious diseases, dyskeratosis, Grover's disease, sub-cutaneous pustulosis, cutaneous lichen, morphea, autoimmune bullous dermatosis, subacute cutaneous lupus erythematosus. Furthermore, we try to precise the physiopathogenic mechanisms of these dermatosis and we want to draw the attention on these dermatoses which sometimes need a multidisciplinary approach.

Delayed effects of accidental cutaneous radiation exposure: fifteen years of follow-up after the Chernobyl accident. J Am Acad Dermatol. 2003 Sep;49(3):417-23.

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. Am J Surg Pathol 2002;26:328-337

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.

Postirradiation Pseudosclerodermatous Panniculitis. Am J Dermatopathol 2001;23:283-287.

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.

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