DIABETIC DERMANGIOPATHY

Necrobiosis Lipoidica Diabeticorum (NLD) and Pigmented Pretibial Patches (PPP) are characterized by their association with diabetes mellitus, by their pretibial predilection, and by vascular alterations compatible with diabetic microangiopathy. Despite differences in the gross and microscopic morphology, both may be considered part of a spectrum of cutaneous lesions for which the term diabetic dermangiopathy is suggested. Variants within this spectrum are reported, including 2 cases with widespread lesions of PPP, occurring in areas other than pretibial.     

Dermatologic perivascular hemophagocytosis: a report of two cases

Hemophagocytic syndrome includes fever, hepatosplenomegaly, cytopenias, coagulopathy, and abnormal liver function tests, with some patients developing lymphadenopathy and cutaneous eruptions. Herein we report two cases of dermal perivascular hemophagocytosis identified in skin biopsies of two patients with no additional symptoms attributable to hemophagocytic syndrome. Biopsies showed capillary ectasia with dermal perivascular infiltrates. The overlying epidermis and adjacent subcutaneous fat was unremarkable. The infiltrate consisted of perivascular neutrophils and benign histiocytes with predominately phagocytized erythrocytes and occasional engulfed karyorrhectic debris. Perivascular nuclear dust (leukocytoclasia) and extravasated erythrocytes were present, but other factors typically found in leukocytoclastic vasculitis were absent, namely fibrin deposition and endothelial hypertrophy and/or necrosis. This appears to be hemophagocytosis, possibly associated with late lesions of leukocytoclastic vasculitis. Both hemophagocytosis and leukocytoclastic vasculitis are associated with activated immunity with increased cytokines and/or immune complexes. It is important to consider this uncommon finding in the evaluation of indeterminate cutaneous eruptions.     

Ultrastructural study of the histogenesis of membranocystic lesions (Nasu) in diabetics

In order to clarify the histogenesis of membranocystic lesion (MCL) of the skin, 14 biopsies obtained from the shins and feet of diabetics were examined by light and electron microscopy. MCL was observed in 10 of 14 cases, including 7 pigmented pretibial patches (PPP), each a case of diabetic bulla, callus of the knee, and ordinary psoriasis. Ultrastructurally, MCL was characterized by 3 fundamental types of structure: tortuous thick bands composed of well-developed minute tubular structures; shrubbery-like structures in sectional profile consisting of accumulated tiny cysts and microprojections; and thin membranes without minute tubular structures. The small vessels in the dermis and subcutaneous tissue indicated the changes of microangiopathy. Present observations suggested that MCL was derived from subcutaneous fat cells and was displaced into the dermis to be disposed by histiocytes. Circulatory disturbance due to diabetic microangiopathy in the subcutaneous tissue could be one of the contributory factors in the formation of MCL.     

Perivascular myoma of myopericytoma and myofibromatosis-type arising in a chronic scar

We describe a case of a cutaneous perivascular myoma with features overlapping between the myofibromatosis and the myopericytoma type. The patient is a 58-year-old woman with a painless plaque-like and multinodular lesion in the pretibial dermis and subcutaneous tissue. She had repeated trauma to this site, first in her early youth that left an area of hyperpigmentation, and then again at age 40. The biopsy showed a biphasic pattern with a myofibromatosis-type component composed of spindle cell myoid nodules and more cellular round cell areas. The myopericytoma-like areas appeared to be infiltrating along vessels. These areas contained aggregates of immature-appearing cells arranged concentrically around vascular lumina in a manner reminiscent of pericytes. Immunohistochemical stains showed focal positivity for smooth muscle actin. Immunohistochemical and ultrastructural studies have showed these pericyte-like cells to be of a myoid origin. The reason for the neoplastic proliferation of perivascular myoid cells is presently unknown. The association of trauma and neoplastic transformation of the skin is rare. We report the first case of a cutaneous perivascular myoma arising in a chronic scar.     

Pseudo-Kaposi's Sarcoma Associated with Acquired Arteriovenous Fistula

Pseudo-Kaposi's sarcoma or acroangiodermatitis usually has underlying conditions of increased venous pressure or circulatory abnormality. We experienced two cases of pseudo-Kaposi's sarcoma in patients with acquired iatrogenic arteriovenous fistula from hemodialysis on their forearms. The patients complained of painful swollen crusted vesicles and purple or erythematous patches or plaques on their hands and fingers. Histologic findings included features of pseudo-Kaposi's sarcoma such as proliferations of small vascular spaces with narrow vascular channels lined by spindle cells, extravasated erythrocytes, and hemosiderin deposits. Percutaneous arteriography performed in Case one excluded the possible coexistence of arteriovenous malformation. In both cases, venous pressure and skin surface temperature were increased around the lesions; these may have played important roles in the development of the lesions. Both cases improved after oral erythromycin treatment, which seemed to be safe and effective for pseudo-Kaposi's sarcoma.     

Purpura as a cutaneous association of sickle cell disease.

A common chronic feature of sickle cell disease is the presence of painful, punched-out leg ulcers. Other cutaneous findings in patients with homozygous sickle cell disease have not been described in the literature. We present a case of a 50-year-old black woman with sickle cell disease who was admitted for acute onset of arm and hip pain. After admission she deteriorated clinically, with multiorgan failure and mental status changes. Examination of the skin revealed erythematous papules and plaques with scaly centers and purpura on the upper trunk. The clinical differential diagnosis was vasculitis versus sepsis. Skin biopsy of two representative lesions was performed. Hematoxylin- and eosin-stained sections showed a superficial perivascular mixed inflammatory infiltrate with numerous eosinophils and extravasated erythrocytes, some of which exhibited bizarre morphology of sickled red blood cells. These findings indicated that the patient's cutaneous lesions, possibly multifactorial in origin, could be a component of her sickle cell crisis. This case is presented as an unusual one in which evaluation of erythrocyte morphology contributed to patient management and to emphasize the importance of examining erythrocyte morphology as a part of the histologic evaluation of stained tissue.     

The nature of hyaline (eosinophilic) globules and vascular slits of Kaposi's sarcoma.

Ultrastructural studies of Kaposi's sarcoma (KS) from skin biopsies of 24 patients (eight with acquired immunodeficiency syndrome (AIDS) and 16 without) were performed to delineate the nature of hyaline globules and vascular slits. These structures have been regarded as one of the important criteria for the recognition of KS under light microscopy. Histochemical and immunochemical studies were also performed to correlate with the electron microscopic (EM) observations. The most remarkable EM findings of KS were the intracytoplasmic lumen formation and erythrophagocytic activities of the neoplastic cells, particularly in the mature nodular, or neoplastic stage. The spindle-shaped or ovoid neoplastic cells frequently contained one to several intact and fragmented red blood cells. The intracellular and extravasated erythrocytes were often arranged in single files, giving these vascular slits an elongated appearance on longitudinal sections. The phagocytic activities of the neoplastic cells were demonstrated by the presence of membrane-bound lysosomes containing phagocytized erythrocytes and their partially digested forms (erythrophagosomes) adjacent to pinocytotic vesicles, prominent rough endoplasmic reticulum, and Golgi apparatus, as well as scattered, small, membrane-bound lysosomal granules, some of which were attached to the erythrophagosomes. The erythrophagosomes underwent various stages of disintegration. The partially digested red cells varied from 0.4 to 10 microns in diameter. The results of histochemical and immunochemical findings also strongly suggested that erythrophagosomes were most likely the hyaline globules (bodies) seen in light microscopy. The exact mechanism of erythrophagocytosis is uncertain. However, its consequences, erythrophagosomes, and intracytoplasmic lumen formation, particularly in the nodular or neoplastic stage in patients with and without AIDS, are among the important histologic features of KS.     

Type-I cryoglobulinemia-like histopathologic changes in tick bites: a useful clue for tissue diagnosis in the absence of tick parts

BACKGROUND: The histopathologic findings of localized reactions to tick bites may present as diagnostic dilemmas, especially if there is no history of a tick bite, or if the tick's mouthparts are not present in the biopsied skin. OBJECTIVE: Skin biopsies of patients with a clinical history of a tick bite were selected and reviewed with the aim of detecting a common histopathologic denominator which could serve as a useful clue to the diagnosis, especially when the tick's mouthparts are absent. METHODS: Hematoxylin and eosin-stained slides of 15 skin biopsies of tick bites were retrieved from three dermatopathology and pathology laboratories. Where additional paraffin-embedded tissue was available, additional sections were also stained with periodic acid-Schiff (PAS) and phosphotungstic acid-hematoxylin (PTAH). RESULTS: In every case in which adequate tissue was available (13/ 15 biopsies), the capillaries and postcapillary venules of the superficial and deep vascular plexi adjacent to the attachment's site were filled with thrombi. Fibrin thrombi were seen in association with other more numerous thrombi characterized by homogeneous eosinophilic hyaline material similar to the cryoprecipitate present in type I (monoclonal) cryoglobulinemia. All thrombi were positive for PAS and PTAH; however, the latter staining was minimally present in the hyaline thrombi. In most cases, the site of the tick bite showed ulceration, with an underlying wedge-shaped superficial and deep perivascular and occasionally interstitial mixed lymphohistiocytic infiltrate. In addition, there were eosinophils, numerous neutrophils and extravasated erythrocytes. Other findings included suppurative necrosis (7/15) cases, giant-cell reaction (one case), fat necrosis (one case) and eccrine gland necrosis (one case). CONCLUSIONS: Vascular eosinophilic hyaline thrombi were found to be a frequent histologic manifestation of a tick bite. This finding may be related to the secretory products of the tick's saliva during inoculation. We believe that a tick bite should be suspected when focal intravascular hyaline occlusion is observed, and that it should be included in the differential diagnosis of type I (monoclonal) cryoglobulinemia, even if there is no history of a tick bite or if tick parts are not present in the skin biopsy specimen.     

Cutaneous collagenous vasculopathy with generalized telangiectasia: an immunohistochemical and ultrastructural study

We report a 54-year-old male, with a 5-year history of spreading asymptomatic generalized cutaneous telangiectases. The patient had no mucosal or nail involvement, no positive family history and no clinical evidence of systemic disease or bleeding diathesis. Histologically, the superficial small dermal blood vessels were dilated and showed thickened walls with hyaline perivascular material, staining as collagen. The vessel walls were PAS and colloidal iron stain positive, and immuno-histochemically lacked actin staining. Collagen IV, fibronectin and laminin antibodies showed the material deposited around the basement membrane zone. Ultrastructurally, the vessels were post-capillary venules (PCV) and showed marked collagen deposition around the basal lamina. There were many abnormally banded widely spaced fibres with 100-150 nm periodicity (Luse bodies), in addition to regular banded collagen. Pericytes were sparse and lacked intracytoplasmic filaments, and few veil or fibroblastic cells were seen embedded within the collagen. We believe this is a form of cutaneous microangiopathy not previously described, with distinct morphology and unique ultrastructural features. It may be due to a genetic defect with erroneous production of disorganized collagen in the cutaneous microvasculature. Dermatologists and Dermatopathologists should be aware of this unusual cutaneous vasculopathy.     

Clinically uninvolved skin in AIDS: evidence of atypical dermal vessels similar to early lesions observed in Kaposi''s sarcoma

The clinically uninvolved skin of 4 patients with well-developed AIDS was investigated by electron microscopy. All biopsy specimens had vascular abnormalities: protruding endothelial cells, vascular channels reduced to slits, gaps within the vascular walls, and extravasated erythrocytes. These features are similar to those described in early lesions of Kaposi's sarcoma. These findings suggest that blood vessels of the clinically uninvolved skin of AIDS patients are potential sites of Kaposi's sarcoma lesions.     

Nodular spindle cell proliferation in the wall of a varicose vein mimicking Kaposi's sarcoma

Exuberant reparative reactions resembling sarcoma have been reported in the genitourinary tract, thyroid, breast, lymph node, oral cavity and skin, but not in a varicose vein. Presented herein is the case of a 55‐year‐old man who showed an incidental nodular lesion in the wall of a varicose vein on the left leg. The nodule consisted of fascicles of spindled cells with ovoid or elongated nuclei and delicate chromatin that showed diffuse reactivity for CD31, alpha‐smooth muscle actin and D2‐40. This histopathological appearance, when coupled with extravasated erythrocytes and interstitial hemosiderin deposits, resembled Kaposi's sarcoma or spindle cell angiosarcoma. Key features helpful for recognizing that the proliferation we describe is a form of tissue repair include an association with obvious hemorrhage; lack of well‐formed curved fascicles of spindled cells; lack of intracytoplasmic hyaline globules; lack of intracellular vacuolization; cytological blandness; low mitotic count; absence of inmmunoreactivity for human herpesvirus‐8 (HHV‐8) latent nuclear antigen‐1; and absence of HHV‐8 in polymerase chain reaction (PCR) analysis. Val‐Bernal JF, Val D, Garijo MF, Gómez‐Román JJ. Nodular spindle cell proliferation in the wall of a varicose vein mimicking Kaposi's sarcoma.     

Acroangiodermatitis

A 26-year-old man with a history of chronic primary lymphedema of the left lower extremity presented with elephantiasis, confluent, violaceous, mascerated plaques, and ulcers on the dorsal aspects of the toes of the left foot. Histopathologic examination showed a proliferation of small blood vessels associated with extravasated erythrocytes and hemosiderin deposits consistent with the diagnosis of acroangiodermatitis. Treatment of the focal ulcers includes compression therapy, local wound care, and surgical elimination of the shunt if there is an associated arteriovenous malformation.     

Manifestations of Cutaneous Diabetic Microangiopathy

The etiologies of a variety of skin conditions associated with diabetes have not been fully explained. One possible etiological factor is diabetic microangiopathy, which is known to affect the eyes and kidneys in patients with diabetes. There are many mechanisms by which diabetes may cause microangiopathy. These include excess sorbitol formation, increased glycation end products, oxidative damage, and protein kinase C overactivity. All of these processes occur in the skin, and the existence of a cutaneous diabetic microangiopathy has been well demonstrated. These microangiopathic changes are associated with abnormalities of skin perfusion. Because the skin plays a thermoregulatory role, there is significant capillary redundancy in normal skin. In diabetic patients, loss of capillaries is associated with a decrease in perfusion reserve. This lost reserve is demonstrable under stressed conditions, such as thermal stimulation. The associated failure of microvascular perfusion to meet the requirements of skin metabolism may result in diverse skin lesions in patients with diabetes. Many skin conditions peculiar to diabetes are fairly rare. Necrobiosis lipoidica diabeticorum (NLD) and diabetic bullae occur very infrequently as compared with diabetic retinopathy and nephropathy. Conversely, there is a correlation between diabetic microvascular disease and NLD. This correlation also exists with more common skin conditions, such as diabetic dermopathy. This relationship suggests that diabetic microangiopathy may contribute to these conditions even if it is not primarily causal. Clinically, the major significance of diabetic cutaneous microangiopathy is seen in skin ulceration which is very common and has a major impact on diabetic patients. Many factors contribute to the development of diabetic foot ulcers. Neuropathy, decreased large vessel perfusion, increased susceptibility to infection, and altered biomechanics all play a role, but there is no doubt that inadequate small blood vessel perfusion is a major cause of the inability to heal small wounds that eventually results in ulcer formation. The accessibility of skin capillaries makes cutaneous diabetic microangiopathy an attractive model for research on the evolution of microvascular disease in diabetic patients.     

Histology of cutaneous vasculitides

Identification of vasculitis by skin biopsy represents the diagnostic gold standard. Skin biopsies should be taken from fresh lesions or from margin of an ulceration and should contain all layers of the skin including subcutis. Classification of vasculitis is based on histological criteria considering the size of the predominantly affected vessel, the distribution of vasculitis in the dermis and subcutis, and the predominant inflammatory cell-type. In cutaneous vasculitis, small and medium-sized vessels of the arterial and/or venous system are predominant affected. Vasculitis of the larger-sized blood vessels is based on inflammatory cells within the wall of the vessel; in small vessel vasculitis, additional features include fibrin within the vessel wall and/or an intraluminal thrombus and/or perivascular and interstitial infiltrates of neutrophils, nuclear dust and extravasated erythrocytes are required for the diagnosis of vasculitis. Leukocytoclastic vasculitis is the most common form of cutaneous vasculitis. An correct diagnosis requires careful correlation of medical history, the clinical, serological, imaging and direct immunofluorescence data, and histologic findings.     

Diabetic microangiopathy in subcutaneous fatty tissue

To evaluate diabetic microangiopathy in the subcutaneous fatty tissue objectively and to clarify the relation between pathogenesis of membranocystic lesion (MCL) and diabetic microangiopathy, specimens obtained from 23 diabetics and 23 nondiabetics were examined histologically. Ten of 23 diabetics and 7 of 23 non-diabetics were examined electron microscopically. Using electron micrographs measurements were made of the following areas; entire microvessel section, basal laminae, luminal space, endothelial cells, pericytes, and we scored the following findings: veil cells, cellular debris and vacuoles in the thickened basal laminae, abnormal densities of the endothelial cells. In diabetics, the area of luminal space was smaller and the area of basal laminae was larger than those of non-diabetics. Scored assessment of the veil cells, cellular debris and vacuoles in the thickened basal laminae were statistically significant in diabetics. Veil cells around the subcutaneous microvessels were less frequent and possessed fewer cytoplasmic processes than those around the dermal microvessels. Histologically, MCLs were frequently demonstrated in skin disorders resulting from diabetic microangiopathy, including 3 cases of pigmented pretibial patches, and 1 case of diabetic bulla. MCLs were more frequently demonstrated in diabetic cases with retinopathy, neuropathy, and nephropathy than those without complications. MCLs were detected only on the shins and the feet. MCLs were more frequently seen in cases with larger area of basal laminae than those with smaller area of basal laminae in morphometric measurement of electron micrographs. The present studies suggest that microangiopathy in the subcutaneous tissue is a pathological feature of diabetes mellitus and is a contributory factor to the formation of MCL.     

Plasma cell balanitis: clinicopathologic study of 112 cases and treatment modalities

BACKGROUND: Plasma cell balanitis or Zoon's balanitis is an idiopathic benign condition of the genitalia that mostly presents as a solitary, persistent plaque on the glans primarily in uncircumcised, middle-aged to older men. METHODS: One hundred twelve patients with a clinical diagnosis of plasma cell balanitis were studied between January 1985 and April 2003. RESULTS: The age of the patients ranged from 24 to 70 years. The majority of patients had symptoms for more than 12 months. Lesions involved the prepuce and glans in the majority of patients (66; 58.92%), the prepuce only in 26 patients (23.21%), and the glans only in 20 patients (17.85%). Tissue for histopathology was available in 96 patients. Histologically, epidermal edema, a dense upper dermal band of chronic inflammatory cells, including many plasma cells, dilated capillaries, extravasated red blood cells, and hemosiderin deposition, was seen. In most, cases, plasma cell balanitis was successfully treated by circumcision. CONCLUSIONS: This report describes our experience with plasma cell balanitis and reviews its clinical and histopathologic aspects. The treatment modalities are also reviewed, and the importance of circumcision as the treatment of choice is emphasized.     

Histologie der kutanen Vaskulitiden

Identification of vasculitis by skin biopsy represents the diagnostic gold standard. Skin biopsies should be taken from fresh lesions or from margin of an ulceration and should contain all layers of the skin including subcutis. Classification of vasculitis is based on histological criteria considering the size of the predominantly affected vessel, the distribution of vasculitis in the dermis and subcutis, and the predominant inflammatory cell-type. In cutaneous vasculitis, small and medium-sized vessels of the arterial and/or venous system are predominant affected. Vasculitis of the larger-sized blood vessels is based on inflammatory cells within the wall of the vessel; in small vessel vasculitis, additional features include fibrin within the vessel wall and/or an intraluminal thrombus and/or perivascular and interstitial infiltrates of neutrophils, nuclear dust and extravasated erythrocytes are required for the diagnosis of vasculitis. Leukocytoclastic vasculitis is the most common form of cutaneous vasculitis. An correct diagnosis requires careful correlation of medical history, the clinical, serological, imaging and direct immunofluorescence data, and histologic findings.     

Histological differentiation between palmoplantar pustulosis and pompholyx

Background Palmoplantar pustulosis (PPP) is a chronic and intensely inflammatory skin disease with pustules, erythema and scaling localized to the palms and soles. Pompholyx is characterized by recurrent crops of vesicles on the lateral aspects of the fingers and the palms and soles. Because both PPP and pompholyx share similar clinical and histological features, it is difficult to differentiate between these two diseases even for dermatologists. Objective To compare the histological features of PPP and pompholyx and to analyse their clinical characteristics. Methods The clinical history from 45 patients with PPP and 42 with pompholyx was evaluated. Among these patients, the punch biopsies from acute lesions of 40 PPP patients and 35 pompholyx ones were analysed, blind to the clinical diagnosis. Results There was no sexual predilection in either group, and 65.5% of PPP patients had smoking history. About half of the patients had concomitant palmoplantar lesions in PPP and pompholyx respectively. In histological evaluation, loss of granular layer, suprapapillary plates thinning, eosinophils in the pustules or vesicles, tortuous capillaries, capillaries touching the undersurface of epidermis and extravasated erythrocytes were statistically significant features of PPP. Confluent parakeratosis, psoriasiform epidermal hyperplasia, clubbing and anastomosing of the rete ridges favoured PPP. Meanwhile, multiple foci of parakeratosis, irregular epidermal hyperplasia and thinning of rete ridges were more often observed in pompholyx. However, dyskeratotic cells, papillary dermal oedema, dilated capillaries and acrosyringium were not significantly different between the two diseases. Conclusions Several histological features could serve as useful ‘clues’ to differentiate between PPP and pompholyx.     

Cutaneous collagenous vasculopathy: a rare cutaneous microangiopathy

Cutaneous collagenous vasculopathy is a rare microangiopathy of superficial dermal blood vessels. Patients present with telangiectatic macules, predominantly on the extremities. A skin biopsy specimen is necessary to distinguish cutaneous collagenous vasculopathy from generalized essential telangiectasia. Microscopically, cutaneous collagenous vasculopathy resembles the superficial telangiectasias of generalized essential telangiectasia but additionally shows hyaline material in thickened vessel walls. The amorphous pink material is periodic acid-Schiff-positive and resistant to diastase. We describe a series of four patients with cutaneous collagenous vasculopathy and highlight its clinical and histopathologic features.     

Palisaded neutrophilic and granulomatous dermatosis

A 22-year-old woman with mixed connective-tissue disease presented with a 5-month history of recurrent episodes of tender, erythematous papules, nodules, and edematous plaques on the upper extremities and thighs. Cutaneous lesions occurred in the setting of livedo reticularis. A biopsy specimen showed interstitial and perivascular inflammation with lymphocytes, macrophages, neutrophils, nuclear dust, collagen alteration, extravasated erythrocytes, and fibrin within small superficial blood vessels. These changes were consistent with a diagnosis of palisaded neutrophilic and granulomatous dermatosis, which is a rare entity that includes a combination of a neutrophilic infiltrate, abnormal or altered collagen, granuloma formation, and leukocytoclastic debris in the context of an immune-mediated collagen vascular or systemic disease. The underlying mechanism remains poorly understood. Treatment is limited, and resolution of lesions typically occurs within several months to years.