Histological study of necrolytic acral erythema.

Described in 1996, necrolytic acral erythema remains the sole diagnostic cutaneous marker for hepatitis C virus infection. To date only eight cases have been described in literature, a fact that makes full histological description and appreciation of the disease process inadequate. Thirty necrolytic acral erythema cases were biopsied and detailed histological description was performed by three separate dermatopathologists who were blinded as to clinical presentation. Clinicopathological correlation was used to evaluate the disease progress. In the early stage, there is moderate regular acanthosis with variable spongiosis and inflammation, progressing to a picture resembling nummular eczema. In its fully evolved form, necrolytic acral erythema shows psoriasiform epidermal hyperplasia with marked papillomatosis. Associated findings include parakeratosis, focal hypergranulosis, subcorneal pustule, epidermal pallor, necrotic keratinocytes, which sometimes become confluent in the upper epidermis and/or track along the acrosyringia, vascular ectasia and papillary dermal inflammation. Late stage samples display some remaining acanthosis with variable inflammation. Pigment incontinence is seen in all stages.

Leukocytoclastic (small vessel) vasculitis in multiple myeloma.

The hallmark of leukocytoclastic vasculitis (LCV) is palpable purpura. Histologically, there is a neutrophilic, angiocentric, segmental inflammation with endothelial cell injury and fibrinoid necrosis of the blood vessel walls. Leukocytoclastic vasculitis has many associations, including, rarely, multiple myeloma (MM). A total of 2357 patients with a diagnosis of MM were reviewed to retrieve cases that had developed leukocytoclastic vasculitis. Eight patients with MM and LCV showed a predominance of immunoglobulin G (IgG) myeloma paralleling the immunoglobulin secretion seen overall. Overexpression of interleukin 6, which is necessary for myeloma cell growth and survival, may contribute to the pathogenesis of LCV in the setting of MM.

Sweet syndrome in multiple myeloma: a series of six cases.

BACKGROUND: Sweet syndrome (SS), a paraneoplastic syndrome characterized by fever, neutrophilia, multiple erythematous painful plaques, and a dense dermal neutrophilic infiltration, has a known association with hematologic malignancies such as acute myelogenous leukemia. However, no clear association with multiple myeloma (MM) has been reported. MATERIALS AND METHODS: Pathology reports of the 2357 patients with multiple myeloma at the University of Arkansas for Medical Sciences were reviewed to retrieve cases who had developed SS. Cytogenetic studies and immunoglobulin secretory status were retrieved. Five cases of SS in MM and 25 cases of SS in patients without MM underwent syndecan-1 immunohistochemistry. OBSERVATIONS: Six cases of SS occurring in the setting of MM showed a predominance in patients secreting IgG paraprotein. Five of the six patients received granulocyte-colony stimulating factor while the sixth received granulocyte-monocyte-colony stimulating factor. Fifty percent showed a non-specific cytogenetic anomaly. CONCLUSIONS: There is no specific cytogenetic anomaly associated with SS in the setting of MM. This paraneoplastic syndrome may be secondary to elevated levels of granulocyte colony stimulating factor (G-CSF), possibly with a component of enhanced sensitivity to endogenous G-CSF. The immunoglobulin secretory status parallels that seen in MM with cutaneous involvement, but IgG secretors may be at an increased risk of developing SS compared with their counterparts who secrete other immunoglobulins.

AL amyloidosis is not present as an incidental finding in cutaneous biopsies of patients with multiple myeloma.

Multiple myeloma (MM) is a monoclonal B-cell neoplasm characterized by autonomous proliferation of immunoglobulin-secreting plasma cells that are capable of synthesizing amyloidogenic light chains resulting in AL amyloidosis. Clinically occult AL amyloid deposition may occur in up to 31% of patients with MM. The prognosis of combined amyloidosis and MM is improving with new therapeutic options. Thus it is imperative that patients with MM be screened for amyloidosis. Sixty-six consecutive skin biopsies from patients with MM and the diagnosis of graft vs. host disease (GVHD) were stained with Congo red and assessed for the presence of amyloid deposition. Twelve cases that had amyloid deposition in other tissue and had a cutaneous biopsy were also stained with Congo red and assessed for the presence of amyloid deposition. None of the 66 biopsies of GVHD, and none of the 12 cases that had documented amyloid deposition in other tissue showed evidence of amyloid deposition in the cutaneous biopsies. In the absence of specific cutaneous manifestations of amyloidosis, it is unlikely that amyloidogenic light chain deposition in the skin would be found. Type I collagen may appear similar to amyloid, both by light microscopy and fluorescence, after staining with Congo red. Thus care must be taken not to confuse type I collagen autofluorescence with positivity for amyloid when assessing skin biopsies stained with Congo red.

Absence of Borrelia burgdorferi DNA in cutaneous B-cell lymphomas from the United States.

BACKGROUND: An association between Borrelia burgdorferi and cutaneous B-cell lymphoma (CBCL) has been made in several European countries. The evidence in favor of such an association has recently been based on more definitive tests for the pathogenetic role of B. burgdorferi in CBCL, including positive cultures or polymerase chain reaction (PCR) amplification of borrelial DNA from lesional skin. However, there is only one report of B. burgdorferi in four North American cases of B-cell lymphoma. METHODS: We retrieved 38 cases of primary and secondary CBCL from different geographic regions of the United States. Two separate techniques were used to detect borrelial DNA by PCR, a nested PCR method to amplify a B. burgdorferi-specific gene as well as a borrelial chromosomal Ly-1 clone amplification method. Southern blot hybridization was used for confirmation of the PCR results. RESULTS: No B. burgdorferi-specific DNA was detected in any of the 38 CBCL cases, whereas detectable PCR products were obtained with our positive controls. CONCLUSIONS: Our findings, in light of previous studies, suggest that B. burgdorferi plays a minimal role in the development or pathogenesis of CBCL in the United States. The findings also suggest that the geographic variations in the clinical manifestations of B. burgdorferi are indeed real and may be secondary to the genetic and phenotypic differences between B. burgdorferi strains present in Europe and North America.

Expression of the human erythrocyte glucose transporter Glut-1 in areas of sclerotic collagen in necrobiosis lipoidica.

BACKGROUND: Glut-1 is the human erythrocyte glucose transporter which mediates facilitative transport of glucose across epithelial and endothelial barrier tissues. A primary abnormality in glucose transport and Glut-1 cell-surface content has been observed in fibroblasts from NIDDM and obese individuals. With the strong correlation between necrobiosis lipoidica and diabetes mellitus, we investigated the expression of Glut-1 in diabetic individuals with necrobiosis lipoidica (NL). METHODS: A polyclonal anti-Glut-1 antibody was used with a standard immunoperoxidase technique to determine Glut-1 expression by fibroblasts in areas of sclerotic collagen from specimens taken from diabetic individuals with necrobiosis lipoidica,and non-diabetic individuals with scars and granuloma annulare (GA). RESULTS: Our results showed Glut-1 expression in the areas of sclerotic collagen in patients with NL, possibly contributing to insulin resistance in these tissues. CONCLUSIONS: Our findings raises the question as to whether abnormalities in glucose transport by fibroblasts in individuals with necrobiosis lipoidica contribute to the histopathologic changes.

The role of androgen receptors in the clinical course of nevus sebaceus of Jadassohn.

Nevus sebaceus of Jadassohn (NSJ) is a benign, congenital hamartoma that often presents at birth, appears to regress in childhood, and grows during puberty, suggesting possible hormonal control. We studied 18 cases of NSJ from children and adults for immunohistochemical evidence of androgen receptor expression. The lesions were evaluated for location and pattern of immunostaining, and these findings were compared between age groups, sexes, and to androgen receptor expression in normal skin. Androgen receptor positivity was seen in the sebaceous glands, in eccrine glands with and without apocrine change, and rarely in keratinocytes in the sebaceous nevi. There were no significant differences in staining location or pattern between the age groups or sexes. Normal skin showed similar staining in the sebaceous glands but did not show staining of the eccrine glands or keratinocytes. Androgen receptors are present in all epithelial components of NSJ, but there is no change in androgen receptor expression during puberty.

Reassessment of lymphocytic atypia in the diagnosis of mycosis fungoides.

The manifestations of mycosis fungoides in its early stage may mimic clinically and histologically those of many benign inflammatory dermatoses. Therefore, the diagnosis of mycosis fungoides remains a major challenge for dermatologists and dermatopathologists. For many years, it has been proposed that atypical lymphocytes within the epidermis constitute one of the diagnostic features in mycosis fungoides. Presence of dermal atypical lymphocytes remains controversial as a diagnostic criterion. We reassessed the feasibility of applying lymphocytic atypia within epidermis and dermis as diagnostic criteria discriminating between mycosis fungoides and spongiotic dermatitis. Thirty cases of mycosis fungoides and 30 cases of spongiotic dermatitis were retrieved from archival hematoxylin and eosin-stained histologic sections. Punch biopsy sections were examined by light microscopy; epidermal and dermal lymphocytes were photographed at 1000x (oil immersion). A total of 92 ektachrome slides (35 mM) were developed, coded, and ordered randomly. For each slide, cells were interpreted as typical or atypical lymphocytes by seven pathologists. Atypical epidermal lymphocytes were judged to be present in 9 +/- 2 out of 16 (56%) cases of mycosis fungoides photographed as compared with 8 +/- 3 out of 16 (50%) in spongiotic dermatitis. Dermal lymphocytic atypia was thought to be present in 14 +/- 6 out of 30 (47%) patients with mycosis fungoides. Thirteen +/- 6 out of 30 (43%) patients with non-mycosis fungoides also displayed dermal lymphocytic atypia. No statistical significance was observed in these comparisons (t test, P >.05). Furthermore, atypia of lymphocytes was deemed to be present in 41, 38, 59, 70, 23, 47, and 40 out of 92 slides examined by the investigators, suggesting that observer variation is a very significant factor in our present study. We conclude that it is not possible to distinguish mycosis fungoides from spongiotic dermatitis merely based on lymphocytic atypia within epidermis or dermis.

The expression of syndecan-1 is preferentially reduced compared with that of E-cadherin in acantholytic squamous cell carcinoma.

BACKGROUND: Syndecan-1 and E-cadherin are cell adhesion molecules which are expressed primarily on the surface of adult epithelial cells. They appear to be co-regulated and may act in concert to stabilize the epithelium. Loss of expression of both E-cadherin and syndecan-1 is seen in malignant transformation and invasion. METHODS: Thirteen cutaneous biopsies of acantholytic squamous cell carcinoma (SCC) were examined for coexpression of E-cadherin and syndecan-1. RESULTS: Interestingly, immunoreactivity for E-cadherin was increased in the in situ component while immunoreactivity for syndecan-1 was similar to that seen in normal skin. Conversely, in invasive SCC the expression of these two adhesion molecules was very similar. Both diminished with decreasing cell differentiation, as well as in the acantholytic areas where both molecules exhibited increasing cytosolic staining rather than cell membrane staining. CONCLUSIONS: Our results suggest that it is likely E-cadherin and syndecan-1 act in concert to stabilize the epithelium and that the loss or decreased expression of both of these adhesion molecules is associated with malignant transformation.

Acantholysis and spongiosis are associated with loss of syndecan-1 expression.

BACKGROUND: Syndecan-1, a heparan sulfate proteoglycan present on the membrane of keratinocytes, functions in intercellular adhesion. Acantholysis and spongiosis are both characterized by diminished intercellular adhesion that may lead to blister formation. In spongiotic conditions, desmosomal stretching occurs prior to cell separation while in acantholytic conditions, cell separation occurs without stretching. While many of the structural relationships have been described, the molecular interactions regulating keratinocyte to keratinocyte adhesion are not yet fully understood. METHODS: Sections from ten cases of Grover's disease, two pemphigus vulgaris, one pemphigus foliaceus, one bullous pemphigoid, two herpes simplex, and ten spongiotic dermatitis were stained with BB-4, a monoclonal anti-syndecan-1 antibody. RESULTS: Nine of ten Grover's, all three pemphigus, and both herpes cases showed absent or markedly decreased syndecan-1 expression by acantholytic keratinocytes, with a sharp delineation from adjacent unaffected skin. The remaining Grover's case showed moderate loss of syndecan-1 expression. The pemphigus foliaceus case showed retention of staining along the basal cell layer, but expression was lost in the mid stratum spinosum. All ten spongiotic cases showed a diffuse mild decrease in staining, with loss of syndecan-1 expression surrounding microvesicles. Bullous pemphigoid, as expected, did not show loss of syndecan expression. CONCLUSIONS: The loss of syndecan-1 expression evident in acantholytic conditions and, to a lesser extent in spongiotic conditions, may contribute to the decreased intercellular adhesion characteristic of these lesions.

Granuloma annulare: another manifestation of Bartonella infection?

Granuloma annulare (GA) is a common cutaneous eruption whose pathogenesis remains unknown. Recent literature has suggested a relation between Borrelia infection and GA, a relation that has not been widely accepted. Earlier works attempted unsuccessfully to implicate various other infectious agents. Some reports have demonstrated the increased frequency of GA in patients with human immunodeficiency virus infection, again raising the possibility of an infectious etiology. Using polymerase chain reaction amplification, we examined 19 biopsy specimens from 19 patients with GA (14 with classic palisading GA and 5 with an interstitial pattern) for the presence of a 153-base pair sequence specific for Bartonella henselae or Bartonella quintana. None of our patients were known to be human immunodeficiency virus-positive. These primers failed to detect B. henselae and B. quintana DNA in any of the specimens examined. Our findings do not support the hypothesis that GA represents a granulomatous reaction pattern to cutaneous Bartonella infection. Nevertheless, we cannot exclude the possibility that there may be a relation in other geographic locations or in immunocompromised patients or that GA represents an autosensitization reaction in response to a distant site of infection. Additional studies are needed to address these hypotheses.

Characterization of interdigital glands in the Asian elephant (Elephas maximus).

In the Asian elephant, wetness akin to perspiration is commonly observed on the cuticles and interdigital areas of the feet; this observation has lead to speculation regarding the existence of an interdigital gland. Our goal was to search for interdigital glands and characterise them morphologically, histochemically, and immunohistochemically. Necropsy samples of interdigital areas from two Asian elephants were obtained. Multiple sections were fixed and processed routinely, then stained with hematoxylin/eosin and differential mucin stains. Immunohistochemistry was also performed for cytokeratins 8 and 10. Interdigital glands resembling human eccrine glands were detected deep within the reticular dermis. Histochemical staining indicated neutral mucopolysaccharides and nonsulphated acid mucopolysaccharides in glandular secretions, and the glandular epithelium also showed immunoreactivity to cytokeratins 8 and 10. Both the histochemical and immunohistochemical staining patterns are analogous to human eccrine structures. This study shows with certainty that Asian elephants possess sweat glands as they are defined histologically.