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Blood vessels connect the heart to the rest of the body. Oxygenated blood fresh from the lungs enters into the left side of the heart and is delivered via the aorta to the rest of the body. As the vessels become progressively smaller, branching to supply the organs and then finally the cells, arteries turn into arterioles, then finally capillaries. At the capillary level, the lumen narrows to the diameter of about one red cell. Oxygen exchange occurs and oxygen depleted blood returns to the right heart via capillaries, to larger venules, then to veins, and then to the inferior and superior vena cava before it enters into the right heart via the right atrium.

Atherosclerosis-General Information
Reactive Angioendotheliomatosis (RAE)
Venous Leg Insufficiency and Ulcers
Venous Thromboembolism


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Surgical Pathology of the Ascending Aorta: A Clinicopathologic Study of 513 Cases.

*Mayo Medical School daggerDepartment of Laboratory Medicine and Pathology double daggerDivision of Biostatistics, Mayo Clinic, Rochester, MN section signDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Arizona.


Am J Surg Pathol. 2006 Sep;30(9):1159-1168 Abstract quote

Only 2 comprehensive surgical series, published in 1977 and 1983, have evaluated clinicopathologic features of the ascending aorta.

Retrospective review of medical records and microscopic slides was performed on 513 consecutive patients with surgical resection of ascending aortic tissue (1985 to 1999). Patients were 2 to 89 years old (mean 59 y), and 303 (59%) were men. Aneurysm or dissection was the indication for surgery in 479. Aortic valves were also excised in 360. Systemic hypertension was present in 279, inherited connective tissue disease (ICTD) in 67, arteritis in 33, and acquired connective tissue disease in 16. Microscopy showed cystic medial degeneration (CMD) in 209, aortic dissection (AD) in 109 (with CMD in 56), normal media in 90, aortitis in 57 (with CMD in 14), and other findings in 48. The most significant, independent risk factor of CMD and AD was ICTD (confidence interval=7.61 and 2.26, respectively). Systemic hypertension was more common in patients with AD than without (P=0.0202). Normal media was the most common histologic finding associated with bicuspid aortic valve (P<0.0001). Among 57 patients with aortitis (giant cell in 39), ages ranged from 16 to 85 years (mean 64 y), and 42 (74%) were women; only 8 had Takayasu arteritis, and 11 had temporal or systemic arteritis.

In surgically resected ascending aorta, the 3 most common histologic findings were CMD, AD, and normal media. ICTD, systemic hypertension, and bicuspid aortic valve were common comorbid findings. Giant cell aortitis occured predominantly in women, usually without systemic disease.
Localized lymphedema (elephantiasis): a case series and review of the literature.

Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY 12208, USA.


J Cutan Pathol. 2009 Jan;36(1):1-20. Abstract quote

BACKGROUND: Lymphedema typically affects a whole limb. Rarely, lymphedema can present as a circumscribed plaque or an isolated skin tumor.

OBJECTIVE: To describe the clinical and pathologic characteristics and etiologic factors of localized lymphedema.

METHODS: Case-control study of skin biopsy and excision specimens histologically diagnosed with lymphedema and presenting as a localized skin tumor identified during a 4-year period.

RESULTS: We identified 24 cases of localized lymphedema presenting as solitary large polyps (11), solid or papillomatous plaques (7), pendulous swellings (4), or tumors mimicking sarcoma (2). Patients were 18 females and 6 males with a mean age of 41 years (range 16-74). Anogenital involvement was most frequent (75%)--mostly vulva (58%), followed by eyelid (13%), thigh (8%) and breast (4%). Causative factors included injury due to trauma, surgery or childbirth (54%), chronic inflammatory disease (rosacea, Crohn's disease) (8%), and bacterial cellulitis (12%). Eighty-five percent of these patients were either overweight (50%) or obese (35%). Compared with a series of 80 patients with diffuse lymphedema, localized lymphedema patients were significantly younger (41 vs. 62 years old, p = 0.0001), had no history of cancer treatment (0% vs. 18%, p = 0.03), and had an injury to the affected site (54% vs. 6%, p = 0.0001). Histologically, all cases exhibited dermal edema, fibroplasia, dilated lymphatic vessels, uniformly distributed stromal cells and varying degrees of papillated epidermal hyperplasia, inflammatory infiltrates and hyperkeratosis. Tumor size significantly and positively correlated with history of cellulitis, obesity, dense inflammatory infiltrates containing abundant plasma cells, and lymphoid follicles (p < 0.05). A history of cellulitis, morbid obesity, lymphoid follicles and follicular cysts predicted recurrent or progressive swelling despite excision (p < 0.05).

CONCLUSIONS: Localized lymphedema should be considered in the etiology of skin tumors when assessing a polyp, plaque, swelling or mass showing dermal edema, fibrosis and dilated lymphatics on biopsy. A combination of lymph stasis promoting factors (trauma, obesity, infection and/or inflammatory disorders) produces localized elephantiasis.

Lymphangitis of the foot demonstrating lymphatic drainage pathways from the sole.

Uhara H, Saida T, Watanabe T, Takizawa Y.

Department of Dermatology, Shinshu University, School of Medicine, Nagano, Japan.

J Am Acad Dermatol 2002 Oct;47(4):502-4 Abstract quote

BACKGROUND: There are two main lymphatic routes from the lower extremity: the fibular route to the popliteal node and the tibial route to the distant groin node. However, little is known about lymphatics from the sole.

OBJECTIVE: We attempted to obtain detailed knowledge of the lymphatics from the sole.

METHODS: Eight patients with lymphangitis were examined and compared with the drainage patterns visualized by blue-dye injection in 7 cases of melanoma.

RESULTS: Six lymphangitic streaks started from the lateral edge of the plantar surface, 2 from the heel, and 1 each from the center of the sole and the little toe. All streaks ran to the tibial side and went up along the foot branch of the great saphenous vein. These findings were similar to those of the dye-injected melanoma cases.

CONCLUSION: Lymphangitis makes visualization of lymphatic routes possible and may provide useful information about drainage.


Paraneoplastic acral vascular syndrome: epidemiologic features, clinical manifestations, and disease sequelae.

Poszepczynska-Guigne E, Viguier M, Chosidow O, Orcel B, Emmerich J, Dubertret L.

Department of Dermatology, Hopital Saint-Louis, 1 avenue Claude-Vellefaux, 75475 Paris Cedex 10, France.

J Am Acad Dermatol 2002 Jul;47(1):47-52 Abstract quote

BACKGROUND: Acral vascular syndromes associated with malignancy have rarely been reported.

OBJECTIVE: Our purpose was to assess the clinical and evolving features of paraneoplastic acral vascular syndromes. Patients and Methods: Two cases of paraneoplastic gangrene are described and analyzed together with previously reported cases identified by a MEDLINE search.

RESULTS: Among the 68 patients identified, 40 had gangrene, 16 had acrocyanosis, and 12 had Raynaud's phenomenon. The male to female ratio was 0.89; median age was 59 years. Fingers were affected in 94%. Adenocarcinomas were the predominant associated malignancies (41%), and metastases were observed in 41%. The acral vascular syndromes in 48% of the patients definitively regressed after tumor treatment. Forty-four percent of the patients died within 2 years. A favorable cutaneous outcome was obtained with prostacyclin infusions in 6 patients.

CONCLUSION: A neoplastic origin of acral vascular syndrome should be considered in elderly patients, especially men, in the absence of usual causative conditions.


Superficial pseudoaneurysms: clinicopathologic aspects and involvement of extracellular matrix proteoglycans.

Burke AP, Jarvelainen H, Kolodgie FD, Goel A, Wight TN, Virmani R.

Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306, USA.
Mod Pathol. 2004 Apr;17(4):482-8. Abstract quote

The distribution of proteoglycans in 21 temporal and two ulnar artery pseudoaneurysms was studied immunohistochemically. A history of trauma was elicited in six cases, and 16 of the lesions were pulsatile. The clinical diagnosis was aneurysm or cyst in 18 patients, possible arteritis in two patients, tumor in one patient, and unknown in the remaining patient.

Histologically, there was a prominent myxoid neointimal response in the walls of each interrupted artery. The remnant arterial segment was often inconspicuous. Prominent smooth muscle cell proliferation and granulation tissue response with inflammation led to misdiagnosis of tumor or vasculitis, respectively, in 11 cases. Immunohistochemical staining for proteoglycans demonstrated abundant, diffuse versican in interrupted wall segments. Biglycan was confined to collagenized and vascularized areas. In some portions of medial disruption, in which angiogenesis was prominent, decorin was expressed within endothelial cells of neocapillaries.

These findings demonstrate that superficial pseudoaneurysms may be mistaken clinically and pathologically for unrelated entities. The immunohistochemical studies confirm that versican is upregulated in areas of tensile stress. In addition, the presence of endothelial expression of decorin supports the concept of decorin's involvement in angiogenesis.


Smooth muscle pattern is more reliable than the presence or absence of an internal elastic lamina in distinguishing an artery from a vein.

Dalton SR, Fillman EP, Ferringer T, Tyler W, Elston DM.

Department of Pathology, Brooke Army Medical Center and Wilford Hall Medical Center, San Antonio, TX, USA.

J Cutan Pathol. 2006 Mar;33(3):216-9. Abstract quote  

BACKGROUND: Major pathology textbooks suggest that the shape of the vessel and the presence or absence of an internal elastic lamina are the best means to distinguish an artery from a vein. Because the shape of the vessel is highly dependent upon the plane of section, the internal elastic lamina is often cited as a more reliable criterion. After evaluating a patient with superficial thrombophlebitis, in whom these conventional criteria had led to a misdiagnosis of polyarteritis nodosa, we sought to determine whether the pattern of smooth muscle in the media is a more sensitive discriminator between an artery and a vein.

METHODS: Anatomically identified arteries and veins were harvested from extremity amputation specimens and stored autopsy organ specimens and reviewed by two dermatopathologists who were blinded to the gross pathologist's impression. The biopsies were assessed for the smooth muscle pattern and the presence or absence of an internal elastic lamina.

RESULTS: Forty-seven of the 50 cases (94%) were concordant with the pathologist's gross impression using only the smooth muscle pattern to differentiate an artery from a vein. On the basis of the presence or absence of an internal elastic lamina, 41 of 50 cases (82%) were concordant with the prosector's designation of the vessel.

LIMITATIONS: Vessels were harvested from a variety of sites, with lower extremity vessels predominating. There may be some regional variability not addressed in this study.

CONCLUSION: In this study, the pattern of muscle fibers within the vascular media discriminated between arteries and veins better than assessment of the presence or absence of an internal elastic lamina. Although no single criterion is 100% reliable, assessment of both these criteria may minimize the risk of misinterpreting vessels in the deep dermis and subcutis.
A unique case of a benign disseminated angioproliferation combining features of Kaposi's sarcoma and diffuse dermal angioendotheliomatosis

Rainer Kunstfeld, MD
Peter Petzelbauer, MD

Vienna, Austria

J Am Acad Dermatol 2001;45:601-5 Abstract quote

A female patient undergoing chronic hemodialysis had disseminated, violaceous, and partly ulcerated plaques develop on the trunk. Lesions had erupted simultaneously over a period of 4 weeks and resolved within 5 months after steroid treatment.

By histopathology, the papillary dermis was densely filled with blood vessels lined by a single layer of differentiated endothelial cells, a growth pattern resembling diffuse dermal angioendotheliomatosis. In some areas, endothelial cells were spindle shaped and formed discontinuous lumina. Red blood cells were interspersed within these slits, giving the lesions a kaposiform appearance. By immunohistochemistry, endothelial cells reacted with the antibodies anti-von Willebrand factor, anti-CD31, and anti-CD34 and with the lectin Ulex europaeus-1.

The course of the disease combined with the unusual histopathology makes this case a unique form of a benign disseminated kaposiform angioproliferation.

Hemangioblastoma Arising in the Skin

Alan S. Boyd, M.D.; Jing Zhang, M.D., Ph.D.

From the Departments of Medicine (Dermatology) (A.S.B.) and Pathology (A.S.B., J.Z.), Vanderbilt University, Nashville, Tennessee.

Am J Dermatopathol 2001;23:482-484 Abstract quote

Hemangioblastomas are intracranial and intraspinal tumors arising sporadically or in patients with von Hippel-Lindau disease.

To date, hemangioblastomas have not been described in the skin. Proliferating clear cells with a variable vascular component are found histologically. These clear cells stain for neuron-specific enolase but not cytokeratin or epithelial membrane antigen, allowing them to be differentiated from metastatic renal cell carcinoma.

CD31 Relatively specific for vascular differentiation
May mark plasma cells

CD31 Expression in Intratumoral Macrophages A Potential Diagnostic Pitfall

Jesse K. McKenney, M.D.; Sharon W. Weiss, M.D.; Andrew L. Folpe, M.D.

From the Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

Am J Surg Pathol 2001;25:1167-1173 Abstract quote

CD31 (platelet endothelial adhesion molecule, PECAM-1) is generally regarded to be the most sensitive and specific endothelial marker in paraffin sections. We have recently encountered several cases in which intratumoral CD31-positive macrophages were misinterpreted as evidence of a vascular sarcoma.

We therefore reviewed our last 1950 consultation cases with respect to cases in which CD31 immunostains were performed, to determine the frequency of CD31 expression in macrophages in formalin-fixed, paraffin-embedded tissue and how often the presence of these cells was a source of diagnostic confusion. CD31 immunohistochemistry had been performed on 59 of 1950 (3%) of cases.

These 59 cases consisted of both vascular (20 cases) and nonvascular tumors (39 cases). CD31-positive macrophages were distinguished from endothelial or tumor cells by correlation with the morphologic features and the immunohistochemical staining pattern of the cells of interest. In no case was CD31 positivity seen in the lesional cells of a nonvascular tumor. CD31-positive macrophages were identified in 48 of 59 (81%) cases. CD31-positive macrophages were present in 34 of 39 (87%) nonvascular tumors. A vascular tumor was diagnosed or favored by the referring pathologist in 15 of these 39 cases (38%). In 14 of these 15 cases CD31 immunostains were performed by the referring pathologist; 13 (93%) showed CD31-positive macrophages. In 4 of these 14 cases (29%) the misdiagnosis of a vascular tumor was based primarily or in part on the misinterpretation of CD31-positive macrophages as tumor cells. In all cases with CD34 and CD68 immunostains, the CD31-positive macrophages were CD34 negative and CD68 positive.

We conclude that CD31 expression is very common in macrophages. Misinterpretation of CD31-positive macrophages as tumor cells may result in the erroneous diagnosis of a primary vascular neoplasm. Recognition of the characteristic granular, membranous pattern of CD31 expression in macrophages and careful distinction from tumor cells should allow the accurate interpretation of CD31 immunohistochemistry in possible vascular neoplasms. CD31 may also be useful as a nonlysosomal marker of macrophages in formalin-fixed, paraffin-embedded sections.

CD34 Not as specific for vascular differentiation

J Cutan Pathol 2001;28:24-28

May be useful in separating benign versus malignant vascular tumors

Statistically significant difference in the mean labeling index which was much higher for benign tumors (91.6) versus malignant (6.3)


Detection of lymphatic invasion in primary melanoma with monoclonal antibody
D2-40: a new selective immunohistochemical marker of lymphatic endothelium.

Niakosari F, Kahn HJ,
Marks A, From L.

Departments of Pathology
and Dermatology, Sunnybrook and
Women's College
Health Sciences Center, Toronto, Ontario, Canada.
Arch Dermatol. 2005 Apr;141(4):440-4. Abstract quote  

OBJECTIVES: To identify the presence of lymphatic invasion in primary cutaneous melanoma using monoclonal antibody D2-40, a marker of lymphatic endothelium, and to correlate the presence of lymphatic invasion with other clinicopathologic characteristics of the tumors.

DESIGN: Retrospective melanoma case series study comparing conventional hematoxylin-eosin staining with D2-40 immunostaining for detection of lymphatic invasion.

SETTING: Departments of Pathology and Dermatology, Sunnybrook and Women's College Health Sciences Center, University of Toronto, Toronto, Ontario.Patients Forty-four consecutive cases of primary cutaneous melanoma with a tumor thickness greater than 0.75 mm were examined for presence of lymphatic invasion.

RESULTS: Seven (16%) of 44 melanomas showed the presence of lymphatic invasion under immunostaining with D2-40. In 2 cases, subepidermal lymphatic involvement was present; in 5 cases lymphatic invasion was noted within the tumor, including 1 case of additional lymphatic invasion at the invasive edge of the tumor. Lymphatic invasion was not detected on routine hematoxylin-eosin staining. We observed a trend in the association between lymphatic invasion and 2 markers of tumor aggressiveness, namely, a deeper Clark level and increased frequency of ulceration, which suggests that lymphatic invasion detected with D2-40 may indicate a poor prognosis.

CONCLUSIONS: Immunostaining with D2-40 increases the frequency of detection of lymphatic invasion relative to conventional hematoxylin-eosin staining in primary melanoma. Future outcome data will determine the prognostic significance of lymphatic invasion detected by D2-40 immunostaining.
Factor VIII Least specific for vascular differentiation

Expression of FKBP12 in benign and malignant vascular endothelium: an immunohistochemical study on conventional sections and tissue microarrays.

Higgins JP, Montgomery K, Wang L, Domanay E, Warnke RA, Brooks JD, Van De Rijn M.


Am J Surg Pathol 2003 Jan;27(1):58-64 Abstract quote

FKBP12 is a cytosolic FK506 binding protein that interacts with calcineurin and thereby mediates the immunosuppressive effects of FK506. Because initial immunohistochemical staining showed abundant expression of FKBP12 in vascular endothelial cells, we evaluated whether it could serve as a marker for vascular neoplasms. We performed immunohistochemical staining of conventional sections from formalin-fixed, paraffin-embedded tissue from 59 benign and malignant vascular neoplasms using a polyclonal rabbit antiserum against FKBP12.

Western blot analysis of tissue from 6 angiosarcomas showed a single band at 12 kD, consistent with the published molecular weight for the FKBP12 protein. Together, CD31, CD34, and FKBP12 identified all 59 vascular neoplasms in this study. Specificity of immunohistochemical staining was assessed on 1321 tissues represented on 7 tissue microarrays. All proteins were occasionally expressed in non-vascular tissue. Six of 8 vascular neoplasms represented on the arrays stained for FKBP12, as did normal vessels in numerous cores. The polyclonal antiserum shows comparable sensitivity (94.9%) and specificity (96.5%) to CD34 and CD31 and may be a useful additional marker for vascular differentiation.

Because we have evaluated a large number of tissues by tissue microarray, we anticipate that our estimate of the specificity of immunostaining for FKBP12 as a marker for vascular endothelium will be accurate. In addition, our findings may explain the toxic effects of FK506 on vascular endothelium of the kidney.

(Mitogen-activated protein kinase)
(paraffin tissue)

J Am Acad Dermatol 2001;44:Part 1

Strong expression of phosphorylated MAPK in benign endothelial tumors, including capillary hemangioma of infancy and pyogenic granuloma, and greatly decreased expression in angiosarcoma

Infectious endothelial tumors (verruga peruana) stained strongly with this antibody, similar to benign tumors


Human dermal pericytes express 3G5 ganglioside –
A new approach for microvessel histology in the skin

Peter Helmbold, etal.

J Cutan Pathol 2001;28 (4):206-210 Abstract quote

Background: Pericytes cover the abluminal surface of microvessels and play an important role in capillary regulation and pathology. Studies on pericytes have been hindered by the lack of specific markers with which to facilitate microscopic identification of this cell type. Expression of the cell surface 3G5 ganglioside antigen has been reported in cultured retinal and cardiac pericytes. The objective of this study was to determine the usefulness of monoclonal antibody 3G5 as a pericyte marker in human skin.

Methods: Cryosections of 21 skin biopsies were examined by direct fluorescence technique with anti-3G5, anti-von Willebrand factor, anti-a-smooth muscle actin or DNA fluorochrome.

Results: In human dermis, 3G5 expression is limited to pericytes discriminating this cell type from all other cells including smooth muscle cells, myofibroblasts and myoepithelial cells. We found a pericyte: endothelial cell ratio of 1:12.4 (±7.1), and a difference of a-smooth muscle actin expression between the subpapillary plexus and the microvessels of the Stratum reticulare.

Conclusions: 3G5 mAB is an excellent and so far the only reported tool for identification of dermal pericytes by fluorescent light microscopy. Moreover, this is the first report of the application of 3G5 technique to the microvasculature in tissue sections at the light microscopic level.


HAND ISCHEMIA Adopted from Arch Dermatol 2002 Oct;138(10):1296-8
Aneurysm (subclavian and axillary arteries)
Hypercoagulable state
Systemic sclerosis
Lupus erythematosus
Rheumatoid vasculitis
Hypersensitivity vasculitis
TRAUMA Crush injury
Repetitive blunt trauma
Hypothenar hammer syndrome
IATROGENIC Steal syndrome following angioaccess surgery
Radial artery removal for coronary artery bypass grafting
Radial or ulnar artery cannulation
Intra-arterial medication injection:

Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008

Commonly Used Terms

Adventitia-This is the outermost layer which is composed of connective tissue and nerve fibers. In the largest vessels, there is a smaller network of vessels called the vasa vasorum, that allow oxygen rich blood to perfuse the vascular wall.

Elastic lamina-These are layers of elastic fibers which provide elasticity to the vessel wall. There are two layers, an internal elastic lamina just below the intima, and an external elastic lamina, sandwiched between the adventitia and media.

Endothelial cells-These cells form the lining of the blood vessels. They are a dynamic part of blood vessel maintaining the permeability, helping to regulate inflammation, and playing a critical role in blood coagulation and clotting.

Intima-This is the inner lining of the blood vessel formed by the endothelial cells and a small amount of connective tissue.

Media-This is the layer of smooth muscle and elastic fibers which provide much of the strength and elasticity of the vessel.

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Last Updated January 21, 2009

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