DERMATOPATHOLOGY CASES: Self-Assessment Cases: Editor - Dr Sampurna Roy MD

Digital Images of interesting cases that will include the full spectrum of Dermatopathology, presented in the form of quiz.

The answer of the cases include related links and recent abstracts of articles.








Sunday, January 30, 2011

Answer of Dermatopathology Case 85



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Visit: Cutaneous Lesions in Graft versus Host Disease

Abstract:

Clinicopathologic characteristics of cutaneous chronic graft-versus-host diseases: a retrospective study in Korean patients. Int J Dermatol. 2010 Dec;49(12):1386-92.
BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a major complication in long-term survivors of hematopoietic stem cell transplantation (HSCT). Cutaneous manifestations are frequently the presenting features; therefore, the dermatologist needs to be aware of the wide spectrum of cutaneous cGVHD.
METHODS: We retrospectively evaluated patients' characteristics, clinical, and histological features of cutaneous cGVHD and analyzed factors influencing the severity of cutaneous cGVHD in 100 Korean HSCT recipients between January 1, 1995, and December 31, 2007.
RESULTS: Clinical manifestations of cutaneous cGVHD mainly presented as lichenoid (60.0%), sclerodermoid (12.0%), or erythematous maculopapular (22.0%) patterns. Other less common findings included xerosis, dyspigmentation, acquired ichthyosis, eczema, exfoliative dermatitis, alopecia, erythema multiforme-like or keratosis pilaris-like eruption. Among 100 patients, 46 patients were investigated for nail involvement, and 29 (63.0%) of them were accompanied with nail abnormalities. Histologically, characteristic lichenoid lesions were observed in 53%, sclerodermoid in 9%, and acute/chronic overlap syndrome in 28% of patients. We also discovered that HSCT from female donors to male recipients increased the severity of cutaneous cGVHD.
CONCLUSIONS: We report a large study about cutaneous cGVHD in Asian patients. Cutaneous cGVHD presented with a wide spectrum of clinical and histological manifestations.

Early-onset lichenoid graft-vs.-host disease: a unique variant of acute graft-vs.-host disease occurring in peripheral blood stem cell transplant recipients. J Cutan Pathol.2010 May;37(5):549-58. Epub 2009 Oct 15.
BACKGROUND: A complication of stem cell transplantation is chronic graft-vs.-host disease (GvHD), developing months to years after transplant; the two commonest manifestations are lichenoid GvHD and scleroderma. The purpose of this study was to characterize early-onset lichenoid GvHD.
METHODS: A retrospective study identified patients diagnosed with early-onset lichenoid GvHD. This diagnosis was correlated with type of transplant and concurrent or prior episodes of acute GvHD.
RESULTS: Patients in whom a sex mismatch was present between donor and recipient were included, representing a study population of 17. All received an allogeneic peripheral blood stem cell transplant (PBSCT). All patients had biopsy proven lichenoid GvHD within 60 days or less following transplantation. All had concurrent gastrointestinal symptoms which was biopsy proven GvHD in thirteen of the cases. FISH XY studies revealed that the infiltrating lymphocytes were of donor origin in 12 of the cases, mixed in three and of host origin in two cases.
CONCLUSIONS: Early-onset lichenoid GvHD is exclusive to the PBSCT setting and appears to be mediated by donor lymphocytes, reflecting the higher numbers of donor T cells encountered in PBSCT. We consider this reaction pattern a distinctive subtype of acute GvHD.

Clinical update on graft-versus-host disease in children. Semin Cutan Med Surg.2010 Jun;29(2):92-105.
The last decade has yielded many significant advances in hematopoietic transplantation techniques, immunomodulatory prophylaxis, and diagnostic and treatment approaches to acute and chronic graft-versus-host disease (GVHD). Unfortunately, GVHD remains the cardinal complication in allogeneic hematopoietic stem cell transplantation, with significant associated rates of morbidity and mortality. In this review, we highlight the numerous strides that have been made in making hematopoietic transplantation more successful and provide an update on the clinical and histopathological features of both acute and chronic GVHD in the pediatric population. It is critical for dermatologists to be aware of the characteristic features of cutaneous acute and chronic GVHD and to remain up to date on the evolving spectrum of these conditions. We discuss 5 cases with clinico-pathologic correlation to illustrate the key concepts and principles underlying the diagnosis and management of both acute and chronic GVHD.

Lichenoid exanthema mimicking graft-versus-host disease associated with obstructive lung disease in a non-transplanted patient. Eur J Dermatol. 2010 May-Jun;20(3):381-5. Epub 2010 Mar 19.
Lichenoid graft-versus-host disease (GVHD) is commonly observed in patients who have received donor lymphocyte infusions or allogeneic bone marrow transplantation (BMT). Here we report a striking case of lichenoid GVH-like exanthema in a young woman without any history of blood transfusions or BMT. A polymorphous, multiforme-like exanthema was observed after systemic antibiotic therapy of bronchitis and was initially diagnosed as drug eruption. Later on, disseminated lichenoid papules were noticed on the trunk and extremities with all histologic and clinical characteristics of lichenoid GVHD. Cutaneous GVH-like disease developed, as did obstructive lung disease. Pulmonary as well as skin disease were both refractory to various immunosuppressive therapies. The immune pathogenesis that caused the skin and lung disease in this patient remains unclear. Multiple pregnancies with two abortions with the potential induction of microchimerism may play a role in the disease pathogenesis.

Isomorphic cutaneous graft-versus-host disease reaction after ultraviolet exposure: clinical, histological and direct immunofluorescence studies of four allo-transplanted patients. J Eur Acad Dermatol Venereol.2009 Aug;23(8):913-8.
BACKGROUND: Acute and chronic graft-versus-host disease (GVHD) continues to be a major limitation to successful haematopoietic stem cell transplantation. If experimental studies and clinical observations could partially elucidate the pathophysiology of acute GVHD, the biology of chronic GVHD is still much less well understood.
OBJECTIVES: The aim of this study is to describe a peculiar photoinduced rash which triggered acute and then chronic lesions of GVHD in four allogenic haematopoietic-transplanted patients and discuss the possible aetiology and treatment.
PATIENTS/METHODS: Four patients, two children and two adults affected by either mild or severe chronic GVHD, developed an erythematous rash on sun- or narrow-band ultraviolet B-exposed area, which triggered the onset of acute lesions of GVHD. Any of the patients presented neither a history of photosensitivity nor circulating autoantibodies nor urinary/fecal porphyrine.
RESULTS: The histopathologic findings were characterized by an interface dermatitis with sparse perivascular infiltrate of lymphocytes and scattered necrotic keratinocytes, especially in the upper part of epidermis. Direct immunofluorescence studies excluded lupus-like pattern, revealing nests of fluorescent bodies at the dermal-epidermal junction and in papillary dermis.
CONCLUSIONS: This peculiar isomorphic reaction of cutaneous GVHD after sun or narrow-band ultraviolet B exposures is described, and the possible mechanism involved is discussed. It may represent an interesting model of progression of chronic GVHD, starting with an acute stage and ending up with chronic clinical and histological findings, especially considering that there is no animal model that fully replicates all of the features of chronic GVHD in humans.

Dermatopathology Case 85

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Case 85

A 35 year old male with skin lesions. Patient has a history of hematopoietic stem cell transplantation.

Answer of Dermatopathology Case 84


Polymorphous Light Eruption

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Abstracts

Polymorphous light eruption.Photodermatol Photoimmunol Photomed.2008 Jun;24(3):155-61.

Polymorphous light eruption is the most common photodermatosis, with a prevalence of as high as 10-20% in Western Europe and in the USA. It starts during the second and third decades of life. Although not life-threatening it can severely impair the quality of life, in particular during leisure activities and in outdoors workers. Polymorphous light eruption belongs to the group of so-called idiopathic photodermatoses. This term denotes dermatoses that occur in otherwise healthy individuals from exposure to sunlight or artificial light without the intervention of an exogenous photosensitizing agent. These diseases have two factors in common: they are precipitated by ultraviolet or visible radiation; and their exact pathomechanism remains obscure but is presumably immunologic in nature.

Marked papillary dermal edema--an unreliable discriminator between polymorphous light eruption and lupus erythematosus or dermatomyositis. J Cutan Pathol. 2010 Apr;37(4):416-25.

BACKGROUND: The clinical differential diagnosis of photo-distributed papules and plaques includes polymorphous light eruption (PMLE) and lupus erythematosus (LE). These entities share many histopathological features. However, in most contemporary textbooks, a broad band of papillary dermal edema is reported to be characteristic of PMLE and not seen in LE. Nonetheless, older reports describe papillary dermal edema in LE, including acute cutaneous LE (ACLE) in patients with systemic LE (SLE) and early lesions of discoid lupus erythematosus (DLE). Older reports also describe papillary dermal edema in microscopic sections of dermatomyositis (DM).
METHODS: Retrospective review.
RESULTS: Nine cases of LE (including two patients with acute lesions of SLE, six with DLE and one unclassifiable) and three cases of DM were identified in which sections showed striking papillary dermal edema. Attributes of chronicity, such as epidermal atrophy, follicular plugging and basement membrane thickening, were present concurrently in many sections.
CONCLUSIONS: Marked papillary dermal edema does not reliably distinguish PMLE from LE as it can be seen in ACLE, early and late lesions of DLE and DM. This phenomenon has been underemphasized in recent reports and textbooks. Furthermore, papillary dermal edema in chronic lesions of DLE has not been previously reported.

Pinpoint papular polymorphous light eruption in Asian skin: a variant in darker-skinned individuals. Photodermatol Photoimmunol Photomed. 2009 Apr;25(2):71-4.

BACKGROUND: Polymorphous light eruption (PMLE) is the most common idiopathic but probably immunologic photodermatosis and has wide morphological variants.
METHODS: The photobiological features of all patients diagnosed with the pinpoint papular variant of PMLE at a tertiary dermatology centre in Singapore over a five-year period were retrospectively examined.
RESULTS: Twenty-one patients were reviewed from 2003 to 2007. There were 11 (52.4%) Chinese, four (19%) Malays, five (23.8%) Indians and one (4%) Cambodian. 14 (66.7%) were males and seven (33.3%) were females. The face/neck (48%) and arms/forearms (95%) were most often affected. Nineteen (90.5%) had Fitzpatrick skin phototype IV and two (9.5%) had skin phototype V. Six (28.6%) had decreased minimal erythema dose (MED) to ultraviolet B (UVB) light only, one (4.8%) had decreased MED to ultraviolet A (UVA) light only and one had decreased MED to both UVA and UVB. Four patients had photoprovocation test done, of which three had positive testing to UVA and one had negative testing to both UVA and UVB. Two histological subtypes were found in our patients, one showing perivascular dermatitis and the other consistent with lichen nitidus.
CONCLUSION: Our data suggest that pinpoint papular PMLE is not uncommon in darker-skinned individuals in our cohort.

Pinpoint papular variant of polymorphous light eruption: clinical and pathological correlation. J Eur Acad Dermatol Venereol.2006 Apr;20(4):406-10.

BACKGROUND: Polymorphous light eruption (PMLE) is the most common chronic idiopathic photodermatosis usually manifesting as a papular eruption along with several other morphological variants including a pinpoint papular variant.
METHODS AND MATERIALS: Between June 1998 and August 2003, 10 PMLE patients presented to the Department of Dermatology at Henry Ford Hospital with complaints of a pruritic pinpoint papular eruption associated with sun exposure. In six patients skin biopsies were performed along with a detailed history and complete skin examination. We correlated the histology with the clinical course of disease corresponding to acute and subacute disease presentation. We also performed immunohistochemistry on three cases to study the immunophenotype in PMLE.
RESULTS: The clinical, histologic and immunostain findings are summarized. Acute: Clinically pinpoint papules and vesicles, some with erythematous base, were seen. Histology showed focal vesicle formation, spongiosis, oedema, red blood cells extravasation, and superficial and deep perivascular and interstitial lymphocytic infiltrate with occasional eosinophils. Subacute: Clinically pinpoint papules with or without erythema were seen. Histology of the pinpoint lesion showed a nodular collection of lymphocytes and histiocytes with claw-like extension of epidermal rete ridges at the lateral boundaries of the lesion. Overlying epidermal atrophy with adjacent spongiosis, exocytosis, oedema and a superficial perivascular lymphocytic infiltrate and parakeratosis was also observed. The histologic differential diagnosis included lichen nitidus. Immunohistochemical stains revealed the following results: CD8, CD68 positive, CD4 variable (strongly positive to negative) and S-100 negative.
CONCLUSION: (i) Pinpoint papular variant of PMLE is a distinct entity, which shows characteristic histology corresponding to the clinical course of the disease (acute and subacute). (ii) The histologic and immunophenotypic differential diagnosis of this variant during the subacute phase includes lichen nitidus.

Dermatopathology Case 84

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Case 84

Small pruritic papules on the dorsum of the hands and forearms of a 25 year old male. The patient has a history of exposure to bright sunlight for many hours.

Friday, January 28, 2011

Answer of Dermatopathology Case 83

Gouty Tophus

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Asymptomatic nodule on an elderly lady's thumb tip. Hautarzt. 2011 Jan 26.

A 71-year-old woman presented with an asymptomatic growing dermal tumor on her thumb. Clinical picture, ultrasound, laboratory investigations and histology were consistent with the diagnosis of gouty tophus. Pathogenesis, risk factors and therapy of tophaceous gout are discussed.

Gouty tophus of the upper eyelid. Ophthal Plast Reconstr Surg. 2008 Sep-Oct;24(5):404-6.

A 64-year-old man with gout presented with history of an enlarging mass in the left upper eyelid causing mechanical ptosis. The patient underwent excisional biopsy. The histopathologic findings confirmed the diagnosis of gouty tophus of the eyelid.

Role of Melanocortin Receptors in the Regulation of Gouty Inflammation. Curr Rheumatol Rep. 2011 Jan 18.

Gouty arthritis is a form of acute joint inflammation provoked by joint deposition of urate crystals. Although this acute pathology resolves after a few days, the marked degree of inflammation in the joint and-possibly more important to the patient-the excruciating pain it causes require proper therapeutic management. Often deemed a "poor sibling" of chronic joint pathologies such as rheumatoid arthritis and psoriatic arthritis, the increasing incidence of gout makes it a more palatable disease for novel drug discovery programs. This fact, associated with novel insights into the molecular mechanisms activated by the urate crystal deposition, is at the basis of new therapeutics under clinical development for gout, a valid example being the effective targeting of the proinflammatory cytokine interleukin-1. Here we briefly review the current status of antigout drug development and propose another target; our focus is on melanocortin receptor agonists as novel therapeutics for gout and inflammatory arthritides, a prototype of which, the adrenocorticotropic hormone, is already used in clinical settings.

Cellular characterization of the gouty tophus: a quantitative analysis. Arthritis Rheum.2010 May;62(5):1549-56.

OBJECTIVE: To characterize the cellular architecture of the tophus and to determine the presence of cytokines implicated in the initiation and resolution of gouty inflammation.
METHODS: Sixteen fixed, paraffin-embedded, uninfected tophus samples were surgically obtained from 12 patients with microscopically proven gout and were analyzed by quantitative immunohistochemistry. The number of cells present in the corona and fibrovascular zones of the tophus was analyzed by Genmod mixed models analysis.
RESULTS: Numerous CD68+ mononucleated and multinucleated cells were present within the corona zone. Mast cells were identified in all tophus samples and at similar densities throughout the corona and fibrovascular zones. In contrast, neutrophils were rarely observed. Plasma cells were present in very high numbers within the corona zone. The overall number of CD20+ B cells was much lower. However, in 6 of 12 patients (50%), at least 1 B cell aggregate was present in the fibrovascular zone. Large numbers of cells expressing interleukin-1beta (IL-1beta) were observed in the corona zone. Transforming growth factor beta1 (TGFbeta1)-expressing mononucleated cells were also identified. The number of CD68+ cells correlated with the number of cells expressing IL-1beta (r = 0.691, P = 0.009) and the number expressing TGFbeta1 (r = 0.518, P = 0.04).
CONCLUSION: The tophus represents a complex and organized chronic inflammatory tissue response to monosodium urate monohydrate crystals involving both innate and adaptive immune cells. The coexpression of IL-1beta and TGFbeta1 suggests that both proinflammatory and antiinflammatory factors present within the tophus contribute to a cycle of chronic inflammation, attempted resolution, and tissue remodeling.

Large Epidemiologic Studies of Gout: Challenges in Diagnosis and Diagnostic Criteria. Curr Rheumatol Rep.2010 Dec 17.

Large epidemiologic studies of gout can improve insight into the etiology, pathology, impact, and management of the disease. Identification of monosodium urate monohydrate crystals is considered the gold standard for diagnosis, but its application is often not possible in large studies. Therefore, under such circumstances, several proxy approaches are used to classify patients as having gout, including ICD coding in several types of databases or questionnaires that are usually based on the existing classification criteria. However, agreement among these methods is disappointing. Moreover, studies use the terms acute, recurrent, and chronic gout in different ways and without clear definitions. Better definitions of the different manifestations and stages of gout may provide better insight into the natural course and burden of disease and can be the basis for valid approaches to correctly classifying patients within large epidemiologic studies.

Historical review of gout and hyperuricemia investigations. Nippon Rinsho.2008 Apr;66(4):624-35.

Historical development of gout and hyperuricemia investigations was reviewed. Gout has been a recognized disease since the fifth century B.C. In 1683, Sydenham described the detailed clinical features of the disease based on his own condition. Leeuwenhoek (1679) first described crystals in a gouty tophus, which were identified as uric acid by Wollaston (1797). Since uric acid clearance of hyperuricemia was markedly lower than that in normal controls, early investigators considered that the main cause of hyperuricemia was urate underexcretion. However, in the 1940s, studies on uric acid metabolism using isotope tracer techniques demonstrated that a part of hyperuricemia resulted from urate overproduction, which was detected in approximately one-third of all gouty patients. In the 1970s, micropuncture, microinjection and microperfusion methods as well as stop-flow methods demonstrated that uric acid transports in nephron were suspected to consist of four steps, that were glomerular filtration, reabsorption, secretion and postsecretory reabsorption. The majority of filtrated uric acid was almost completely reabsorbed, followed by secretion and postsecretory reabsorption at a proximal site in the tubulus. Each proportion of transports to the glomerular filtration(100%) was estimated approximately 99%, 50% and 40%, respectively. Subsequently, about 10% of the filtrate was excreted in the urine. The authors (1999) suggested that the secretion rate of hyperuricemic patients was significantly lower than that of normal controls but postsecretory reabsorption was not. Therefore, the decrease in the secretion rate was suspected to be the main cause of underexcretion. Dunkan (1960) reported a family demonstrating hyperuricemia associated with severe renal damage that progressed rapidely. Currently, this disease is called familial juvenile hyperuricemic nephropathy (FJHN), and was recently found to be the result of a variation in uromodulin. Enomoto (2002) found a number of urate transporters in the cell surface of the tubulus, among which URAT1 was the most effective in reabsorbing urate from the tubulus lumen to the cells. The urate was released to the blood vessel side by the other transporter OAT. Therefore, URAT1 was suspected to be a cause of underexcretion. As the mechanism underlying overproduction of uric acid, de novo purine nucleotide synthesis has been shown to be increased. In some cases, the increase in de novo synthesis is the result of gene mutation in purine nucleotide synthesis enzymes, such as PRPP synthetase (Sperling, 1973) as well as hypoxanthine guanine phosphoribosylpyrophosphate synthetase (Seegmiller, 1967). However, the mechanism in majority of the overproduction has not yet been clarified and is currently under investigation.

Dermatopathology Case 83

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Case 83

Slide for spot diagnosis.

Thursday, January 27, 2011

Answer of Dermatopathology Case 82


Rheumatoid Nodule

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Non-infectious granulomatous diseases of the skin and their associated systemic diseases: an evidence-based update to important clinical questions. Am J Clin Dermatol. 2010;11(3):171-81.
Non-infectious granulomatous diseases of the skin are a broad group of distinct reactive inflammatory conditions that share important similarities. As a group, they are relatively difficult to diagnose and distinguish both clinically as well as histologically. Many of these disorders have significant associations with systemic diseases that impact the patient's overall prognosis. In this update, we offer a discussion of emerging concepts and controversies in this field, as presented through evidence-based answers to seven important clinical questions regarding palisading and epithelioid granulomata. These questions offer an opportunity to review ten non-infectious granulomatous conditions that have implications for systemic disease: granuloma annulare, annular elastolytic giant cell granuloma, necrobiosis lipoidica, methotrexate-induced accelerated rheumatoid nodulosis, necrobiotic xanthogranuloma, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, palisaded neutrophilic granulomatous dermatitis, sarcoidosis, and metastatic Crohn disease. Recent clinical, epidemiologic, and laboratory studies have shed some light on these diseases, the association of these conditions with systemic disorders, and their overall prognoses.

Rheumatoid nodule. Semin Cutan Med Surg.2007 Jun;26(2):100-7.
Rheumatoid nodules are the most common extra-articular manifestation of rheumatoid arthritis. Dermatologist may be concerned with the diagnosis and management of rheumatoid nodules, although most patients will probably be under the care of a rheumatologist. This article focuses in clinical, pathogenic, diagnostic, and therapeutic aspects of rheumatoid nodules. Classic rheumatoid nodules commonly occur in genetically predisposed patients with severe, seropositive arthritis. However, they may appear in other clinical settings. Accelerated rheumatoid nodulosis, especially involving the hands, has been reported in patients receiving methotrexate, antitumor necrosis factor alpha biologic drugs or leflunomide therapy for rheumatoid arthritis. Rheumatoid nodulosis is characterized by multiple rheumatoid nodules, recurrent joint symptoms with minimal clinical or radiologic involvement, and a benign clinical course. Pseudorheumatoid nodules have been reported in healthy children. Although histologically almost indistinguishable from true rheumatoid nodules, some consider these lesions to be a form of deep granuloma annulare.

Dermatopathology Case 82

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Case 82

Slide for spot diagnosis.

Answer of Dermatopathology Case 81

Immunohistochemistry: S100 protein is strongly positive.
Immunohistochemistry: CD1a is stongly positive




Abstract:

Langerhans cell hyperplasia of the skin mimicking Langerhans cell histiocytosis: a report of two cases in children not associated with scabies. Fetal Pediatr Pathol. 2010;29(4):231-8.
Langerhans cells histiocytosis (LCH) affecting the skin most commonly has clinical and histopathologic diagnostic features. We are reporting two examples of Langerhans cell (LC) hyperplasia recognized in the skin biopsies of two children initially interpreted as LCH. The first was an 8-year-old boy finally interpreted as having an atypical type of contact dermatitis, while the second, an 8-year-old girl, was assumed to have Pytiriasis lichenoides et varioliformis acuta. None showed evidences of scabies. Both presented spongiotic dermatitis with numerous CD1a+ cells. As more cases of LC hyperplasia are recognized, new details emerge helping in the differential diagnosis. Strict clinical-pathologic correlation is suggested in order to avoid misdiagnosis.

Cutaneous Langerhans cell histiocytosis in an elderly woman. Dermatol Online J. 2010 Oct 15;16(10):6.
Langerhans cell histiocytosis (LCH) is a clonal proliferative disorder of Langerhans cells typically seen in infants and children. Rare adult cases usually have systemic involvement. We report an uncommon case of skin-limited LCH in an elderly woman, who is to our knowledge one of the oldest patients reported with this condition.

Skin-limited Langerhans' cell histiocytosis in children. Cancer Invest. 2009 Jun;27(5):504-11.
Langerhans' cells are dendritic cells derived from precursors in the bone marrow. They constitute 2-4% of the resident epidermal cells and are found within the epidermis above the basal layer. They function as immunologic cells by recognizing antigens and presenting them to T cell lymphocytes. Langerhans' cell histiocytosis is a rare pathology characterized by an abnormal clonal proliferation of Langerhans' cells that infiltrates different organs of the human body. The proliferating Langerhans' cells appears to be primarily responsible for the clinical manifestations. The stimulus for their proliferation is unknown. Among different organs, cutaneous involvement is encountered in 40% of cases. The aim of this investigation is to review the clinicopathologic, immunologic and ultrastructural features of skin-confined Langerhans' cell histiocytosis in children through seven case series. Four boys and two girls with age range of 1 year to 8 years presented with scaling, crusted papules, nodules and papulonodular lesions (two cases each). The locations included the face (three cases), scalp, trunk and vulva (one case each). The histological features included histiocytic reaction (one case), granulomatous reactions (three cases) and both granulomatous and histiocytic reactions (two cases). The diagnosis was confirmed by histochemical (S-100 + CD1a +) and ultrastructural studies (Birbeck granules). Langerhans' cell histiocytosis is a rare disease with pleomorphic cutaneous clinical expressions. Three types of skin lesions usually occur: nodules (common), scaling, or crusted papules (next in frequency) and finally soft, yellow papular xanthomas (rare). Three types of histological pictures are seen: histiocytic, granulomatous (common) and xanthomatous (rare) in children.

Langerhans cell histiocytosis in a premature baby presenting with skin-isolated disease: case report and literature review. Acta Paediatr. 2008 Dec;97(12):1751-4. Epub 2008 Aug 27.
Langerhans cell histiocytosis (LCH) in premature babies is extremely rare as is a vesicular skin rash, while gastrointestinal involvement is associated with a poor outcome. We report a case of LCH in a premature baby presented with isolated vesiculo-papulo-macular skin lesions and insidiously developed gastrointestinal symptoms, haematological and severe pulmonary involvement. We also reviewed a few cases of LCH in premature babies in the English language medical literature. LCH in preterm babies appears to be a severe systemic disease, usually lethal in-utero or post delivery. CONCLUSION: Careful observation should be applied to newborns with skin-only Langerhans cell histiocytosis in order to identify in time progression to potentially fatal systemic disease.

Dermatopathology Case 81

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Case 81

A 4 year old child with multiple yellow-brown scaly papules on the scalp. Erythematous macules and papules are also present on the neck and back. The child is small for age and there is marked loss of weight. He is also accompanied by anaemia, fever and lymphadenopathy.

Wednesday, January 26, 2011

Dermatopathology Case Index: Case 61 to Case 80


Dermatopathology Quiz - Case Index


Case 61 = Targetoid Hemosiderotic Hemangioma (Hobnail Hemangioma)

Case 62 = Chondroid Syringoma

Case 63 = Cutaneous Sarcoidosis

Case 64 = Dermatofibrosarcoma Protuberans

Case 65 = Trichilemmal Carcinoma

Case 66 = Melanocytic Nevus of the Vulva (Site specific nevus)

Case 67 = Lichen Amyloidosus

Case 68 = Scabies

Case 69 = Dermatophyte Infection (Dermatophytoses) - Superficial filamentous Infection (Tinea - ringworm)

Case 70 = Cutaneous Malakoplakia

Case 71 = Grover's Disease

Case 72 = Cutaneous Leishmaniasis

Case 73 = Cutaneous Histoplasmosis

Case 74 = Atrophie Blanche (Livedoid Vasculopathy)

Case 75 = Granuloma Faciale

Case 76 = Perniosis (Chilblains)

Case 77 = Psoriasis

Case 78 = Pustular Psoriasis

Case 79 = Alopecia Areata

Case 80 =Nodular Vasculitis (Erythema Induratum, Bazin-type)

Answer of Dermatopathology Case 80


Nodular Vasculitis (Erythema Induratum, Bazin-type)

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Abstract:

Erythema induratum of Bazin. Dermatol Online J.2010 Apr 15;16(4):1.
An 81-year-old woman with a history of renal cell carcinoma and years of slowly, progressively enlarging pulmonary nodules of uncertain etiology presented with several weeks of painful lower extremity nodules. A biopsy revealed changes consistent with nodular vasculitis. A purified protein derivative and QuantiFERON test were positive, favoring the diagnosis of erythema induratum of Bazin. Treatment with a standard four-drug antituberculous regimen resulted in radiographic and clinical improvement. This case emphasizes the importance of dermatologic manifestations in the detection of systemic disease.

Vasculitis in erythema induratum of Bazin: a histopathologic study of 101 biopsy specimens from 86 patients. J Am Acad Dermatol. 2008 Nov;59(5):839-51.
BACKGROUND: Erythema induratum of Bazin is a mostly lobular panniculitis. There is considerable controversy in the literature about whether or not vasculitis is a histopathologic requirement to establish the diagnosis of erythema induratum of Bazin. Even accepting vasculitis as a histopathologic criterion, there is no agreement about the nature and size of the involved vessels.
OBJECTIVE: The main goal of our study was to investigate whether or not vasculitis was present in a large series of cases of erythema induratum of Bazin and, when vasculitis was found, to determine the nature and localization of the involved vessels.
METHODS: We studied 101 skin biopsy specimens from 86 patients with clinicopathologic diagnosis of erythema induratum of Bazin. Histopathologic criteria required in each case to be included in this study were: (1) a mostly lobular panniculitis with necrotic adipocytes at the center of the fat lobule; (2) inflammatory infiltrate within the fat lobule mostly composed of neutrophils in early lesions and granulomatous infiltrate in fully developed lesions; (3) significant fat necrosis; and (4) absence of other histopathologic findings that allow a specific diagnosis of other lobular panniculitis different from erythema induratum of Bazin. We also recorded the nature of the inflammatory cells involving the fat lobule, and the lesions were classified into two main categories: (1) early lesions, when the inflammatory infiltrate was mainly composed of neutrophils, with or without leukocytoclasis; and (2) fully developed lesions, when histiocytes and lipophages were the predominant inflammatory cells within the involved fat lobule.
RESULTS: Some type of vasculitis was evident in 91 cases (90.09%). A total of 47 biopsy specimens (46.5%) showed a mostly lobular panniculitis with necrotizing vasculitis involving the small vessels, probably venules, of the center of the fat lobule. Thirteen biopsy specimens (12.8%) showed a mostly lobular panniculitis with vasculitis involving both large septal veins and small vessels, probably venules, of the center of the fat lobule. Twelve biopsy specimens (11.8%) showed a mostly lobular panniculitis with vasculitis involving large septal veins, with no involvement or other septal or lobular vessels. Ten biopsy specimens (9.9%) showed a mostly lobular panniculitis with vasculitis involving large septal vessels, both arteries and veins, and necrotizing vasculitis involving the small vessels, probably venules, of the center of the fat lobule. Nine biopsy specimens (8.9%) showed a mostly lobular panniculitis with vasculitis involving large septal vessels, both arteries and veins, but with no involvement of the small blood vessels of the center of the fat lobule. Finally, 10 biopsy specimens (9.9%) showed a mostly lobular panniculitis without evidence of septal or lobular vasculitis in serial sections. Associated diseases included history of extracutaneous tuberculosis (including tuberculosis of the lung, lymph nodes, kidney, or bowel) in 12 cases (13.95%), previous episodes of superficial thrombophlebitis of the lower legs in 3 cases (3.72%), rheumatoid arthritis in one case (1.16%), Crohn disease in one case (1.16%), chronic lymphocytic leukemia in two cases (2.32%), hypothyroidism in two cases (2.32%), and positive serology for hepatitis B virus in 4 cases (4.65%) and for hepatitis C virus in 5 cases (5.81%).
LIMITATIONS: Serial sections were not performed in all cases. At least 10 sections were studied in each case. When vasculitis was evident in some of these first 10 sections, no further sections were cut, but when histopathologic features of vasculitis were not found in the first 10 sections, serial sections throughout the specimen were performed looking for vasculitis. Because some type of vasculitis was evident in the first 10 sections of 91 cases, serial sections were performed only in the remaining 10 cases and they failed to demonstrate clear-cut histopathologic features of vasculitis. On the other hand, this is a retrospective study that was performed from the histopathologic slides of our files, and only the clinical information contained in the report accompanying the biopsy specimen could be recorded.
CONCLUSIONS: In our experience, vasculitis is present in most lesions of erythema induratum of Bazin, and the nature, location, and size of the involved vessels is, from more to less frequent, as follows: (1) small venules of the fat lobule; (2) both veins of the connective tissue septa and venules of the fat lobule; (3) only veins of the connective tissue septa; (4) veins and arteries of the connective tissue septa and venules of the fat lobule; and (5) veins and arteries of the connective tissue septa. However, in some cases with all clinicopathologic features of erythema induratum of Bazin vasculitis could not be demonstrated with serial sections throughout the specimen and, therefore, the presence of vasculitis should be not considered as a criterion sine qua non for histopathologic diagnosis of erythema induratum of Bazin.

Nodular vasculitis in systemic lupus erythematosus. Int J Dermatol. 2008 Nov;47 Suppl 1:3-6.
A 42-year-old man presented with fever, photosensitivity, headaches, myalgia, hyperhidrosis, muscle weakness, alopecia, nasal crustae, weight loss, painful nails, arthritis, oral ulcers, erythema, discoid cutaneous lesions, and painful subcutaneous nodes. We made a diagnosis of systemic lupus erythematosus (SLE), type II cryoglobulinemia, and nodular vasculitis. In the skin, different types of vasculitis may be observed. Typically, histology shows leukocytoclastic vasculitis of superficial vessels both in SLE and mixed cryoglobulinemia, which clinically results in palpable purpura. In our patient, however, histopathological examination of the subcutaneous nodes not only revealed leukocytoclastic vasculitis of the superficial vasculature but also showed even more extensive involvement of dermal and subdermal small and medium sized vessels, giving rise to a nodular vasculitis.

Dermatopathology Case 80

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Case 80

A 55 year old woman with firm, tender erythematous nodules on the calves.

Monday, January 24, 2011

Answer of Dermatopathology Case 79


Alopecia Areata

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Abstract:

'Follicular Swiss cheese' pattern--another histopathologic clue to alopecia areata.J Cutan Pathol. 2011 Feb;38(2):185-9.
Yellow dots are the most useful dermoscopic criterion in the clinical diagnosis of alopecia areata and correspond histopathologically with dilated follicular infundibula. They are found in about 95% of alopecia areata cases and help to differentiate alopecia areata from trichotillomania, telogen effluvium and from scarring alopecias. Histopathology of alopecia areata differs with disease activity and dermatopathologist, therefore, heavily depends on other diagnostic features. Objective of the study was to determine the frequency of dilated follicular infundibula, peribulbar lymphocytic infiltrate, inflammatory infiltrates of lymphocytes and eosinophils within fibrous streamers and a shift to catagen/telogen follicles in alopecia areata. Histopathologic features of 56 specimens of 33 patients were correlated with clinical findings and alopecia areata subtype. Results: 57% of all biopsies showed dilated follicular infundibula, regardless of horizontal or vertical sectioning of the slides. Dilated follicular infundibula showed a maximum occurrence of 66% in the recovery stage of alopecia areata and were seen in 33% of alopecia areata incognita. In conclusion, dilated follicular infundibula, reminiscent of a Swiss cheese in horizontally sectioned slides, is an exceedingly useful criterion in the histopathologic diagnosis of alopecia areata and are of great help in the daily routine to recognize alopecia areata.

Histopathologic features of alopecia areata: a new look. Arch Dermatol. 2003 Dec;139(12):1555-9.
BACKGROUND: A peribulbar lymphocytic infiltrate is the expected histologic feature of alopecia areata, but it is absent in many scalp biopsy specimens. Other diagnostic criteria are needed.
OBJECTIVE: To establish the histologic features of alopecia areata in scalp biopsy specimens taken from different types of alopecia areata, using follicular counts to relate biopsy findings to stages of the disease.
METHODS: Fifty consecutive new patients with alopecia areata were studied. Four-millimeter punch biopsy specimens were taken from the scalp in areas of recent, active hair loss; old, inactive hair loss; or recent hair regrowth. Specimens were sectioned horizontally. Terminal and vellus-like hairs were counted. Inflammation and fibrosis around lower and upper follicles were rated.
RESULTS: The histopathologic features of alopecia areata were not significantly affected by the sex, age, and race of the patient or by the type, percentage of hair loss, total duration, or regression of alopecia areata. The major factor affecting the histopathologic features was the duration of the current episode of alopecia areata. In the acute stage, bulbar lymphocytes surrounded terminal hairs in early episodes and miniaturized hairs in repeated episodes. In the subacute stage, decreased anagen and increased catagen and telogen hairs were characteristic. In the chronic stage, decreased terminal and increased miniaturized hairs were found, with variable inflammation. During recovery, increasing numbers of terminal anagen hairs from regrowth of miniaturized hairs and a lack of inflammation were noted.
CONCLUSIONS: The histopathologic features of alopecia areata depend on the stage of the current episode. Alopecia areata should be suspected when high percentages of telogen hairs or miniaturized hairs are present, even in the absence of a peribulbar lymphocytic infiltrate.

Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol. 2010 Feb;62(2):177-88, quiz 189-90.
Alopecia areata (AA) is an autoimmune disease that presents as nonscarring hair loss, although the exact pathogenesis of the disease remains to be clarified. Disease prevalence rates from 0.1% to 0.2% have been estimated for the United States. AA can affect any hair-bearing area. It often presents as well demarcated patches of nonscarring alopecia on skin of overtly normal appearance. Recently, newer clinical variants have been described. The presence of AA is associated with a higher frequency of other autoimmune diseases. Controversially, there may also be increased psychiatric morbidity in patients with AA. Although some AA features are known poor prognostic signs, the course of the disease is unpredictable and the response to treatment can be variable. Part one of this two-part series on AA describes the clinical presentation and the associated histopathologic picture. It also proposes a hypothesis for AA development based on the most recent knowledge of disease pathogenesis. LEARNING OBJECTIVES: After completing this learning activity, participants should be familiar with the most recent advances in AA pathogenesis, recognize the rare and recently described variants of AA, and be able to distinguish between different histopathologic stages of AA.

Dermatopathology Case 79

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Case 79

A 24 year old male with a few small round patches of hair loss on the scalp. "Exclamation-mark" hairs are seen at the margin of the patch. Sections of the scalp biopsy from the patch.

Sunday, January 23, 2011

Answer of Dermatopathology Case 78

Pustular Psoriasis

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Abstracts:

The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. J Cutan Pathol. 2010 Dec;37(12):1220-9.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) represents a severe, acute, pustular skin reaction that is most often induced by drugs. AGEP can be difficult to differentiate from generalized pustular psoriasis (GPP) both clinically and histopathologically. We present a systematic description of the histopathological spectrum of AGEP and GPP with a focus on discriminating features.
MATERIALS AND METHODS: A retrospective, descriptive, comparative histopathological study was completed utilizing step sections of 43 biopsies of 29 cases with a validated diagnosis of probable or definite AGEP and 24 biopsies of 19 cases with an established diagnosis of GPP.
RESULTS: In AGEP, biopsies from erythema and pustules showed minor differences, whereas histopathology of the acute stage of GPP showed major differences compared to the chronic stage. Comparing AGEP and GPP, the presence of eosinophils, necrotic keratinocytes, a mixed interstitial and mid-dermal perivascular infiltrate and absence of tortuous or dilated blood vessels were in favor of AGEP. Moreover, chronic GPP was characterized by prominent epidermal psoriatic changes. The frequency of a psoriatic background of AGEP patients in our study was higher than that of psoriasis in the general population. However, histopathology of a subgroup of AGEP patients with a personal history of psoriasis revealed no significant differences from the other AGEP patients.
CONCLUSIONS: The spectrum of histopathological features of both AGEP and GPP is presented. Despite considerable overlap, subtle consistent histopathological differences and the grade of severity of specific features can help in differentiation. We could neither substantiate earlier reports that follicular pustules exclude AGEP nor did we see vasculitis as a specific feature in AGEP. Our study also supports the concept that AGEP is a separate entity that is distinct from GPP.

A comparison of Ki-67 antigen presentation in acute generalized exanthematous pustulosis and pustular psoriasis. Arch Dermatol Res. 2010 Sep;302(7):525-9. Epub 2010 Mar 25.

Ki-67 is an established marker of cell proliferation. It is highly expressed in psoriasis and correlated with the clinical severity of psoriasis. Higher number of Ki-67 positive keratinocytes has been observed in pustular psoriasis (PP) as compared with psoriasis vulgaris. As for Acute generalized exanthematous pustulosis (AGEP), a distinct disease entity but similar in many aspects of clinicopathologic features to PP, Ki-67 immunostaining presentation has never been investigated before. This study aimed to compare Ki-67 immunostaining presentation between PP and AGEP. By immunohistochemical staining, we compared Ki-67 immunostaining presentation on skin lesions of five patients of AGEP and five age-matched patients of PP. Ki-67 positive keratinocytes were counted and mean values were determined to compare between PP and AGEP. An augmented presence of Ki-67 positive keratinocytes was found in both AGEP and PP and they distributed not only in basal cell layer but in middle or even upper part of epidermis. Statistical analysis using Mann-Whitney U test showed no difference of epidermal proliferation rate between the two groups (P = 0.222). The results showed there was no difference of Ki-67 immunostaining presentation between AGEP and PP. Besides, we found marked increase of Ki-67-positive proliferating keratinocytes in AGEP and suggested that epidermal hyperproliferation may also play an important role in the formation of AGEP. We also discussed the possible pathophysiology of AGEP, possible epidermal architecture changes in AGEP and PP, and found the similarity in pathophysiology of AGEP and PP.

Generalized pustular psoriasis of pregnancy successfully treated with cyclosporine. Indian J Dermatol Venereol Leprol. 2009 Nov-Dec;75(6):638.

Two multigravidae aged 27 and 29 years, with previous uneventful pregnancies, second being psoriatic, reported at 24 and 28 weeks of pregnancies, with generalized pustular lesions. Laboratory findings, including serum calcium were normal. Ultrasonography showed normal fetal growth. Histopathology confirmed pustular psoriasis. Patients were put on cyclosporine 3 mg/ kg weight/ day after failure of an initial systemic steroid. Blood pressure, pulse, and fetal heart sounds were recorded every 12 hours, and ultrasonography and blood parameters, biweekly. Cyclosporine was tapered and stopped after delivery of two healthy babies at 38 weeks. We conclude that cyclosporine can be an option in the management of pustular psoriasis of pregnancy or psoriasis with pustulation in pregnancy.

Dermatopathology Case 78

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Case 78

A 50 year old male with clearly defined pustules on the skin. The lesions are painful. The patient also complains of fever and malaise.

Friday, January 21, 2011

Answer of Dermatopathology Case 77


Psoriasis

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Abstract:

Scalp psoriasis: an overview of the disease and available therapies.J Drugs Dermatol. 2010 Aug;9(8):912-8.
The scalp is one of the regions of the body most commonly affected by psoriatic lesions. While the head represents only 10 percent of the body's surface area, the consequences of scalp psoriasis are disproportionate to the area, as it can be seriously debilitating and presents social and emotional distress to the affected individual. Scalp lesions are often well-demarcated and may have thick gray or white scale; patients with scalp psoriasis frequently complain of pruritus and shedding of scale. Current treatment modalities--including phototherapy, topical corticosteroids, topical vitamin D analogues and conventional systemic therapies--have produced unsatisfactory results for patients with moderate-to-severe scalp psoriasis due to difficulties in administration to the disease site, poor compliance, toxicity and inadequate long-term efficacy. The emergence of biologic therapies as an effective modality for the treatment of plaque psoriasis may provide another option for patients suffering from plaque psoriasis of the scalp.

Diagnosis of nail psoriasis: importance of biopsy and histopathology. Br J Dermatol.2005 Dec;153(6):1153-8.
BACKGROUND: Involvement of the nail is quite common in psoriasis and at times may be the sole diagnostic clue. However, the histopathology of nail psoriasis has not been adequately evaluated. A confirmation of the diagnosis is required in cases suspected to have nail psoriasis in order to plan long-term therapy.
OBJECTIVES: To assess the diagnostic significance and safety profile of nail biopsy in cases with nail psoriasis.
METHODS: Clinical and mycological features were studied in 42 patients with nail psoriasis. Of these, 22 patients gave consent for nail biopsies to be taken and the histopathological changes were assessed.
RESULTS: Males were affected more commonly (57%) with a peak incidence in the age group of 10-20 years (29%). Distal onycholysis, discoloration of nail plate, subungual hyperkeratosis and fine nail pitting were the predominant clinical features. In the 22 biopsies done, hyperkeratosis with parakeratosis (91%) was found to be the most common and hypergranulosis was the least common histological finding (36%). Clinicohistological correlation was possible only in 55% cases. Periodic acid-Schiff (PAS) staining was done for all biopsies.
CONCLUSIONS: Histopathological examination of nails is a valuable diagnostic aid, especially in the absence of skin lesions. Examination of the PAS-stained sections is necessary before making a histological diagnosis of nail psoriasis because onychomycosis and psoriasis may show similar histology.

Psoriasis triggered by mefloquine. Skinmed. 2010 Sep-Oct;8(5):301-2.
A 46-year-old Caucasian man living on the central Mediterranean island of Gozo (Malta) was started on mefloquine 250 mg once weekly before a trip to lower Egypt. He took his medication 1 week before starting his holiday and was advised to continue it for 4 weeks after returning. He did not take any other medication and enjoyed the holiday, which he initially intended to repeat in the near future. His medical history revealed a number of episodes of psoriasis for which he sought dermatologic advice. He had been given systemic therapy on at least one occasion, but the condition had been fairly quiescent for some time and he had not needed to consult a dermatologist for more than 4 years. Soon after the third tablet of mefloquine and effectively just after his return home to Gozo, the patient noticed that the psoriasis was "creeping back." He noted progressive deterioration in his skin problem but nevertheless finished the recommended course of therapy considering that "being sure about not developing malaria was far more important than a touch of psoriasis." The psoriasis worsened to the extent that he had taken off work for 2 weeks from his job as a self-employed carpenter at the time of referral. On examination, clearly there was a significant flare up of his psoriasis with severe involvement of the hands (Figure 1) and feet and less so over the rest of his body. He had been off work and matters were steadily getting worse in spite of topical treatment with a combination of calcipotriol-betamethasone ointment. Oral methotrexate 15 mg once weekly was commenced together with topical therapy with good results (Figure 2).

Increased Prevalence of Human Papillomavirus in Hairs Plucked From Patients With Psoriasis Treated With Psoralen-UV-A. Arch Dermatol. 2004 Mar;140(3):317-24.
BACKGROUND: Patients with psoriasis treated with psoralen-UV-A (PUVA) are at increased risk of skin cancer; however, the exact causes of this increased incidence are not well understood. It has been suggested that PUVA may increase expression of the tumorigenic agent human papillomavirus (HPV) in skin by directly stimulating virus replication, immune suppression, or both, thereby leading to skin cancer formation. OBJECTIVE: To determine whether HPV DNA prevalence in the skin is increased after long-term PUVA treatment. DESIGN: Screening for the presence of HPV sequences in DNA isolated from plucked body hairs of patients with psoriasis with a history of PUVA exposure and a history of skin cancer (group A), PUVA exposure and no history of skin cancer (group B), and no PUVA exposure and no history of skin cancer (group C). SETTING: University hospital.Patients and METHODS: Hair samples were obtained from 81 patients with psoriasis (56 men and 25 women; mean age, 52 years), including 16 in group A (mean number of PUVA exposures, 702), 35 in group B (mean number of PUVA exposures, 282), and 30 in group C. DNA was isolated from the hair samples and analyzed by polymerase chain reaction with the use of 2 nested primer systems specific for epidermodysplasia verruciformis-associated or related and genital or mucosal virus types, respectively. RESULTS: The rate of HPV DNA positivity was significantly higher in groups A (73% [11/15]) and B (69% [24/35]) than in group C (36% [10/28]) (A + B vs C, P =.009; chi(2) test; age adjusted).Conclusion The prevalence of HPV in the skin (hair follicles) is increased in patients with psoriasis who have a history of PUVA exposure.

Dermatopathology Case 77

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Case 77

Small red dry patches on both elbows of a 45 year old woman. Patient complains of intense itching.

Wednesday, January 19, 2011

Answer of Dermatopathology Case 76


Perniosis (Chilblains)

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Abstract:

Perniosis: clinical and histopathological analysis. Am J Dermatopathol. 2010 Feb;32(1):19-23.
Perniosis are inflammatory cutaneous lesions, located on acral skin, which present in association with cold exposure. They can appear as an idiopathic dermatosis or with an underlying autoimmune disease. The use of cutaneous biopsy to distinguish between both types is controversial. We analyze the histological findings in 9 cases of idiopathic perniosis (IP) and compare them with those obtained from 11 cases of perniosis associated with an autoimmune disease (autoimmune perniosis). The most frequent histopathological features observed in cases of IP were a lymphocytic infiltrate with perivascular (8 cases, 89%) and perieccrine distribution (6 cases, 66%), dermal edema (5 cases, 55%), and necrotic keratinocytes (5 cases, 55%), whereas those found in perniosis associated with an autoimmune disease were lymphocytic infiltrate with perivascular distribution (11 cases, 100%) but without perieccrine distribution (3 cases, 27%), vacuolation of the basal layer (7 cases, 63%), and necrotic keratinocytes (5 cases, 45%). The only significant difference between both groups was the perieccrine distribution of the lymphocytic infiltrate in cases of IP, which, as mentioned in previous studies, could be considered a histopathological clue to differentiate both types of perniosis.

Idiopathic perniosis and its mimics: a clinical and histological study of 38 cases. Hum Pathol 1997 Apr;28(4):478-84.
Perniosis is a term applied to cold-induced painful or pruritic erythematous or violaceous acral papular or nodular lesions.
We examined 39 skin biopsies from 38 patients who presented with acral purpuric lesions, suggesting a diagnosis of perniosis clinically or pathologically. The presence of a systemic or extracutaneous disease was established in 17 patients, including 5 with systemic lupus erythematosus (SLE), 3 with antiphospholipid antibodies, in 1 in whom there was underlying HIV disease, 2 with viral hepatitis, 2 with rheumatoid arthritis (RA), 2 with cryofibrinogenemia, 1 with hypergammaglobulinemia, 1 with iritis, and 1 with Crohn's disease. In the other 21 patients, the clinical presentations prompted further studies in 12, which showed a positive antinuclear antibody (ANA) in 10. A diagnosis of idiopathic perniosis (IP) was rendered in all 21 of these patients including those in whom a positive ANA was discovered, based on the absence of any other serological markers, signs, or symptoms indicative of a specific systemic disease complex; many had Raynaud's phenomenon, small joint arthralgias, atopy, or a family history of either connective tissue disease or Raynaud's disease.
The histopathology of IP comprised a superficial and deep angiocentric lymphocytic infiltrate with papillary dermal edema and lymphocytic exocytosis directed to retia and acrosyringia. A few cases showed a mild vacuolopathic or lichenoid interface dermatitis, adventitial dermal mucinosis, lymphocytic eccrine hidradenitis, vascular ectasia, and thrombosis confined to dermal papillae capillaries.
The biopsies from patients with iritis, RA, and Crohn's disease showed a granulomatous vasculitis and a granuloma annulare-like tissue reaction. The biopsies from the patients with SLE, cryofibrinogenemia, primary antiphospholipid antibody syndrome, and hypergammaglobulinemia shared a similar histopathology comprising an interface dermatitis, superficial and deep angiocentric and eccrinotropic lymphocytic infiltrates, vascular ectasia, and dermal mucinosis with prominent involvement of the eccrine coil.
Many cases did not show features of IP, namely papillary dermal edema, thrombosis of dermal papillary capillaries, and lymphocytic exocytosis into the retia and acrosyringia. There was frequent vascular fibrin deposition involving reticular dermal vessels. The latter two variables were statistically significant discriminators between IP and in perniotic lesions observed in the setting of underlying systemic disease.
With respect to the latter, some cases occurred in the setting of cold exposure and were designated by us as "secondary perniosis" (SP), whereas others showed no specific association with cold exposure and were designated as perniotic mimics (PMs) based exclusively on the gross and microscopic morphology of the lesions.

A histologic and immunohistochemical study of chilblains.J Am Acad Dermatol 2001;45:924-9.
Background: The histopathologic diagnosis of chilblains is controversial and the histologic changes are often considered nonspecific, mainly because they are poorly documented. Although a dermal inflammation in chilblains has been noticed, the infiltrate has not yet been characterized.
Objective: Our purpose was to analyze microscopic and immunohistochemical findings in a large series of chilblains and to compare the results with those of lupus erythematosus (LE).
Methods: We included 36 cases of clinically typical chilblains of the hands, of which 17 were thoroughly investigated to rule out cryopathy or LE. Ten biopsy specimens of hand lesions from patients with proven LE were included as controls. All slides were analyzed by conventional microscopy and by immunohistochemistry with anti-CD3, anti-CD20, and anti-CD68 antibodies.
Results: The most characteristic finding in chilblains (47% of cases) was the association of edema and reticular dermis infiltrate that showed a perieccrine reinforcement. Such a combination of changes was not observed in LE. Epidermal changes in chilblains consisted mainly in necrotic keratinocytes in 52% of cases. The comparison of 17 idiopathic chilblains with LE showed significant differences in spongiosis (58% vs 0% respectively), vacuolation of basal layer (6% vs 60%), edema of the dermis (70% vs 20%), and deep perieccrine inflammation (76% vs 0%). Immunohistochemistry showed that the infiltrate was composed of a majority of T cells associated with macrophages and a few B lymphocytes. The same pattern was observed in both chilblains and LE.
Conclusion: Our results show that a predominantly T-cell papillary and deep infiltrate with a perieccrine reinforcement, associated with dermal edema and necrotic keratinocytes, are the hallmarks of chilblains of the hands. These changes can help differentiate idiopathic perniosis from LE; immunohistochemistry is of no use in differentiation.

Dermatopathology Case 76

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Case 76

A 19 year old girl with bluish red, painful and itchy papules on the toes. She was exposed to extremely cold temperature in the winter season.

Tuesday, January 18, 2011

Answer of Dermatopathology Case 75


Granuloma Faciale

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Abstract:

Granuloma faciale with disseminated extra facial lesions. Dermatol Online J.2010 Jun 15;16(6):5.
Granuloma faciale (GF) is a rare cutaneous disorder categorized as a localized form of small vessel vasculitis. Clinically, it manifests as single or multiple, well-demarcated, red-brown plaques, papules and nodules, nearly always confined to the face. Herein, we report a 39-year-old man with multiple red-brown, infiltrated plaques on his face and extrafacial lesions on the back, shoulders, and both arms. Skin biopsy revealed typical histopathological findings of GF. The patient failed to respond to pulsed dye laser, but intralesional triamcinolone combined with cryotherapy led to an acceptable response.

Granuloma faciale: Case report and review. Dermatol Online J. 2009 Dec 15;15(12):3.
Granuloma faciale (GF) is a rare benign chronic inflammatory dermatosis usually appearing only on the face. The lesions of GF typically present as single, asymptomatic, erythematous, non-changing nodules or plaques. We present an illustrative case of GF and briefly review available treatment options.

Granuloma faciale. Pathologica. 2007 Oct;99(5):306-8.
Granuloma faciale is a rare, benign skin condition that usually occurs on the face. Using an exemplary case of granuloma faciale, we will present the clinical and histological characteristics of this dermatosis. A 49-year-old man presented with a 6-month history of a 10 mm-diameter asymptomatic papulo-nodular red-brown lesion of the nose. A biopsy specimen led to the diagnosis of granuloma faciale. The patient received a session of pulsed-dye laser therapy, which led to significant improvement. This benign and usually isolated dermatosis can more rarely be extrafacial. It may often be mistaken for other benign dermatoses (sarcoidosis, discoid lupus erythematosus) as well as for malignant dermatoses (lymphoma, basal cell carcinoma).

Dermatopathology Case 75

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Case 75

A 52 year old man with a solitary,well-demarcated asymptomatic, brown-red plaque on the face.

Monday, January 17, 2011

Answer of Dermatopathology Case 74



Atrophie Blanche (Livedoid Vasculopathy)


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Abstract:


Livedoid vasculopathy as a coagulation disorder. Autoimmun Rev. 2010 Dec 22.
Livedoid vasculopathy is an occlusive cutaneous disease of the dermal vessels with pauci-inflammatory or non-inflammatory histopathology findings. It is characterized by the presence of macules or papules, erythemato-purpuric lesions located on the legs, especially on the ankles and feet, which produce ulcerations that are intensely painful and originate ivory atrophic scars called "atrophie blanche". In this review article, studies on LV from the literature are analyzed, and their etiopathogenic associations, particularly those related to the thrombophilic states, as well as the pathologic findings and therapeutic approaches applied in the difficult clinical management of these cases, are evaluated.


Livedoid vasculopathy with underlying subcutaneous necrotizing venulitis in an asymptomatic hepatitis B virus carrier: is livedoid vasculopathy a true nonvasculitic disorder? Am J Dermatopathol. 2009 May;31(3):293-6.
Livedoid vasculopathy has been accepted as a nonvasculitic disorder, but authentic vasculitis in the underlying subcutis can occur in cases of collagen disease and polyarteritis nodosa. We report a case of livedoid vasculopathy with underlying subcutaneous necrotizing venulitis in a 42-year-old carrier of hepatitis B virus. The patient also had a 15-year history of ankylosing spondylitis that was currently in remission. Skin lesions revealed superficial ulceration, purpura, atrophie blanche, and reticulate erythema on the lower extremities, and a skin biopsy showed a minimal dermal perivascular lymphocytic infiltrate with marked fibrin thrombi and fibrin deposits along luminal vessel walls, consistent with features of livedoid vasculopathy. However, necrotizing venulitis characterized by a predominant lymphocytic infiltrate in and around the vessel wall with marked fibrinoid vessel wall necrosis was found in the underlying subcutaneous tissue. A direct immunofluorescence study detected immunoglobulin M and C3 deposits in the papillary dermis. The patient responded well to oral aspirin and a prostaglandin analogue and was well controlled with a compression bandage. Vasculitic lesions in the underlying subcutis may have been overlooked in cases in which livedoid vasculopathy has been considered as a nonvasculitic disorder because our case demonstrates that livedoid vasculopathy can be accompanied by subcutaneous vasculitis.


Idiopathic atrophie blanche. Skinmed. 2006 May-Jun;5(3):151-4.
A 41-year-old woman presented with a 3-year history of purpuric lesions followed by superficial, painful ulcers and development of lesions on the lower legs and on the dorsa of the feet, particularly in the summer. The patient was asymptomatic during the winter months. On physical examination she had irregular, scleroatrophic, white-ivory, coalescent lesions on a livedoid basis, with purpuric and, in some lesions, pigmented borders with numerous telangiectatic capillaries. These lesions were localized on the medial sides of the lower legs and on the dorsa of the feet (Figure 1). Laboratory investigations were normal or negative, including complete blood cell count, platelets, coagulation indexes, erythrocyte sedimentation rate, serum immunoglobulins, antinuclear antibodies, anti-double-stranded DNA, anticardiolipin, antiphospholipids, antineutrophilic cytoplasmic antibodies, circulating immunocomplexes, complement fractions (C3, C4), cryoglobulins, rheumatoid factor, and Rose-Waaler reaction. The only laboratory abnormality was an elevated fibrinogen level (472 mg/dL). Doppler velocimetry excluded a chronic venous insufficiency. Thoracic x-ray and abdominal ultrasound were normal. A digital photoplethysmograph revealed functional Raynaud's phenomenon. A biopsy specimen taken from a purpuric lesion showed an atrophic epidermis with parakeratosis and focal spongiosis. An increased number of small-sized vessels were observed within a sclerotic dermis. Most of the vessels in the upper dermis were dilated and showed endothelial swelling; some were occluded due to amorphous hyaline microthrombi (Figure 2). There were fibrinoid deposits around the vessels with thickening of the vessel walls. Extravasated erythrocytes were found throughout the upper and mid-dermis. There was a sparse perivascular lymphocytic infiltrate but no vasculitis. Direct immunofluorescence showed a perivascular microgranular deposit of IgM (+), C3 (++), and fibrinogen/fibrin (+++). On the basis of clinical, serologic, histopathologic, and immunopathologic findings, a diagnosis of idiopathic atrophie blanche was made. The patient was treated with dapsone (50 mg p.o. q.d.) and pentoxifylline (400 mg p.o. t.i.d.) with pain relief and complete resolution of the ulcerations after 6 weeks of therapy.