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.

Friday, October 1, 2010

Answer of Dermatopathology Case 73

Histochemistry : Methenamine silver stain shows Histoplasma capsulatum fungi.

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Histoplasmosis Presenting as a Cutaneous Malignancy of the Eyelid. Ophthal Plast Reconstr Surg. 2010 Sep 20.

Cutaneous histoplasmosis is an uncommon infection and can occur as a primary infection. A manifestation imitating a cutaneous neoplasm is rare, and eyelid involvement is rarer still. The authors report a case of histoplasmosis that presented as an ulcerated lesion on the lower eyelid margin that clinically resembled a basal cell carcinoma. Given its worldwide distribution, it is important to include this disease in the differential diagnosis of nonhealing eyelid lesions. Biopsy and tissue culture are paramount to establishing the diagnosis. This case describes a rare presentation of histoplasmosis on the eyelid and highlights the importance of histopathologic evaluation.

Primary Cutaneous Histoplasmosis in a HIV-Positive Individual.J Glob Infect Dis.2010 May;2(2):112-5.

A 31-year-old human immunodeficiency virus-positive male who presented to the Dermatology Outpatient Department with complaints of red, raised lesions on the face of 2 weeks duration was, on examination, found to have multiple papulonodular lesions on the face with associated cervical and axillary lymphadenopathy. There was history of local injury on the face 6 months prior to the development of symptoms. Skin biopsy revealed multiple round to oval spores with surrounding halo intracellularly, confirming the diagnosis of cutaneous histoplasmosis. No systemic involvement was detected on further investigations. The patient responded to oral antifungals in a short duration, confirming the local nature of the presentation. This is probably the first time in the literature that a primary cutaneous manifestation of histoplasmosis is being described in an immunocompromised individual.

Cutaneous histoplasmosis due to Histoplasma capsulatum variety duboisii in an immune competent child. About one case in Abidjan, Côte d'Ivoire. Bull Soc Pathol Exot.2009 Aug;102(3):147-9.

Histoplasmosis is a subcutaneous mycosis caused by dimorphic fungus which is to be found in two types: the capsulatum and duboisii types. The capsulatum type has had an increasing incidence with the HIV-AIDS epidemics but it is not demonstrated that the duboisii one has had the same upward incidence. Signs in children and immunocompetent patient are rarely described during this disease. The diagnosis is often late in the child as it looks like Molluscum contagiosum lesions. We report a case of skin histoplasmosis of duboisii type non associated with HIV infection in a child. Diagnosis has been confirmed by a histopathological test of a nodule biopsy. Medical treatment was successfully based on itraconazol.

Primary cutaneous histoplasmosis: case report on an immunocompetent patient and review of the literature.Rev Soc Bras Med Trop. 2008 Nov-Dec;41(6):680-2.

This report describes a case of primary cutaneous histoplasmosis in a 45-year-old male. The presentation consisted of an erythematous nodule on the back of the right hand, accompanied by nontender regional lymphadenomegaly that developed following local trauma that occurred during military training in a tunnel inhabited by bats. Histological examination of a biopsy specimen from the skin lesion showed granulomatous infiltrate, but did not show fungal elements. Culturing of this material, incubated in Sabouraud agar, showed growth of Histoplasma capsulatum. No evidence of systemic involvement or immunosuppression was found. Treatment with 400 mg/day of itraconazole orally for six months resulted in complete remission of the lesion, which was maintained one year after the end of the treatment.

Dermatopathology Case 73


Case 73

Spot diagnosis

Tuesday, September 28, 2010

Answer of Dermatopathology Case 72

Cutaneous Leishmaniasis

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Molecular characterization of leishmania species isolated from cutaneous leishmaniasis in yemen. PLoS One.2010 Sep 20;5(9). pii: e12879.

BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected tropical disease endemic in the tropics and subtropics with a global yearly incidence of 1.5 million. Although CL is the most common form of leishmaniasis, which is responsible for 60% of DALYs lost due to tropical-cluster diseases prevalent in Yemen, available information is very limited.
METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted to determine the molecular characterization of Leishmania species isolated from human cutaneous lesions in Yemen. Dermal scrapes were collected and examined for Leishmania amastigotes using the Giemsa staining technique. Amplification of the ribosomal internal transcribed spacer 1(ITS-1) gene was carried out using nested PCR and subsequent sequencing. The sequences from Leishmania isolates were subjected to phylogenetic analysis using the neighbor-joining and maximum parsimony methods. The trees identified Leishmania tropica from 16 isolates which were represented by two sequence types.
CONCLUSIONS/SIGNIFICANCE: The predominance of the anthroponotic species (i.e. L. tropica) indicates the probability of anthroponotic transmission of cutaneous leishmaniasis in Yemen. These findings will help public health authorities to build an effective control strategy taking into consideration person-to-person transmission as the main dynamic of transmission of CL.

Viability and burden of Leishmania in extralesional sites during human dermal leishmaniasis.PLoS Negl Trop Dis.2010 Sep 14;4(9). pii: e819.

BACKGROUND: The clinical and epidemiological significance of Leishmania DNA in extralesional sites is obscured by uncertainty of whether the DNA derives from viable parasites. To examine dissemination of Leishmania during active disease and the potential participation of human infection in transmission, Leishmania 7SLRNA was exploited to establish viability and estimate parasite burden in extralesional sites of dermal leishmaniasis patients.
METHODS: The feasibility of discriminating parasite viability by PCR of Leishmania 7SLRNA was evaluated in relation with luciferase activity of luc transfected intracellular amastigotes in dose-response assays of Glucantime cytotoxicity. Monocytes, tonsil swabs, aspirates of normal skin and lesions of 28 cutaneous and 2 mucocutaneous leishmaniasis patients were screened by kDNA amplification/Southern blot. Positive samples were analyzed by quantitative PCR of Leishmania 7SLRNA genes and transcripts.
RESULTS: 7SLRNA amplification coincided with luciferase activity, confirming discrimination of parasite viability. Of 22 patients presenting kDNA in extralesional samples, Leishmania 7SLRNA genes or transcripts were detected in one or more kDNA positive samples in 100% and 73% of patients, respectively. Gene and transcript copy number amplified from extralesional tissues were comparable to lesions. 7SLRNA transcripts were detected in 13/19 (68%) monocyte samples, 5/12 (42%) tonsil swabs, 4/11 (36%) normal skin aspirates, and 22/25 (88%) lesions; genes were quantifiable in 15/19 (79%) monocyte samples, 12/13 (92%) tonsil swabs, 8/11 (73%) normal skin aspirates.
CONCLUSION: Viable parasites are present in extralesional sites, including blood monocytes, tonsils and normal skin of dermal leishmaniasis patients. Leishmania 7SLRNA is an informative target for clinical and epidemiologic investigations of human leishmaniasis.

Chemokines and chemokines receptors coordinate the inflammatory immune response in human cutaneous leishmaniasis. Hum Immunol. 2010 Sep 17.

Cutaneous Leishmaniasis (CL) includes different clinical manifestations displaying diverse intensity of dermal inflammatory infiltrate. Diffuse CL (DCL) cases are hyporesponsive and lesions show very few lymphocytes and a predominance of macrophages. In contrast, localized CL (LCL) cases are responsive to leishmanial antigen and lesions exhibit granulocytes and mononuclear cell infiltration in its early phases, changing to a pattern with numerous lymphocytes and macrophages later in the lesion. Therefore, different chemokines may affect the predominance of cell infiltration in distinct clinical manifestations. In lesions from LCL patients, we examined by flow cytometry, the presence of different chemokines and their receptors in T cells and we verified a higher expression of CXCR3 in the early stages of LCL (less than 30 days of infection) and a higher expression of CCR4 in the late stages of disease (more than 60 days of infection). We also observed a higher frequency of T cells producing IL-10 in the late stage of LCL. Using immunohistochemistry, we observed a higher expression of CCL7, CCL17 in lesions from late LCL, as well as CCR4 suggesting a preferential recruitment of regulatory T cells in the late LCL. Comparing lesions from LCL and DCL patients, we observed a higher frequency of CCL7 in DCL lesions. These results point out the importance of the chemokines, defining the different types of cells recruited to the site of the infection, which could be related to the outcome of infection as well as the clinical form observed.

The changing profile of cutaneous leishmaniasis in a focus of the disease in Jahrom district, southern Iran. Ann Trop Med Parasitol. 2010 Jul;104(5):377-82.

Human cutaneous leishmaniasis (CL) is endemic in several parts of Iran, and there is an urban focus of the disease in the district of Jahrom, which forms part of the southern province of Fars. To explore the current profile of the disease in Jahrom district, samples were taken from the skin lesions of 40 cases of CL patients in the district, so that the causative parasites could be identified, to species, in a nested PCR. Although Leishmania tropica has been identified, in the past, as the cause of most of the urban CL in Fars province, the predominant species represented in the recent samples from Jahrom district was L. major (87.5%), while L. tropica was relatively rare (12.5%). More than one in every three (35%) of the cases examined was a child aged <10>25 such lesions. The change in the predominant parasite causing CL in Jahrom district, from the L. tropica usually associated with the urban disease in Iran to the L. major more usually associated with CL in rural settings, may well necessitate changes in the local strategies for the prevention and control of CL.

Localized cutaneous leishmaniasis due to Leishmania donovani and Leishmania tropica: preliminary findings of the study of 161 new cases from a new endemic focus in himachal pradesh, India. Am J Trop Med Hyg. 2005 Jun;72(6):819-24.

Localized cutaneous leishmaniasis (LCL) in India is due mostly to Leishmania tropica. It is mainly endemic in the deserts of Rajasthan. Recently, Himachal Pradesh has been identified as a new endemic focus for the disease. In the last few years, the number of new cases has been increasing almost to epidemic proportions. This report presents the preliminary findings of clinico-epidemiologic and investigative results of 161 new localized cases of LCL seen between May 2001 and December 2003. The study populaton was composed of 80 males and 81 females between 10 months and 75 years of age. All were indigenous to the sub-alpine valley along the Satluj River in the mountainous region of the Kinnaur District (altitude = 700-2,900 meters). Most patients were seen from April to September and had 1-8 lesions (duration = 1-6 months) that involved mainly the face. Tissue smears were positive for amastigotes in 37% and histopathology showed non-caseating epitheloid cell granuloma in 77% of the cases. Analysis by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of the ribosomal gene region of 10 biopsy specimens showed amplicons indistinguishable from L. donovani in eight cases and L. tropica in two cases. Leishmania was cultured on modified Nicole-Novy-McNeal (NNN) medium containing RPMI 1640 medium and heat-inactivated fetal bovine serum from 13 of 38 biopsy samples. Three of these isolated strains were identified as L. donovani while a fourth was L. tropica by PCR-RFLP of the ribosomal internal transcribed spacer region. One strain had a gp63 sequence identical to that of east African strains. Another strain had a unique gp63 sequence that has not been found in L. donovani complex strains. Sand flies trapped in the cattle sheds of a few patients were identified as Phlebotomus longiductus (Parrot 1928). Treatment with intralesional sodium stibogluconate was effective in all patients without any major side effects. One patient developed lupoid leishmaniasis that responded to higher dose of sodium stibogluconate. Though rarely reported as a cause of LCL, L. donovani seems to be the predominant pathogen in this new focus of cutaneous leishmaniasis. Phlebotomus longiductus is a possible vector, albeit based on circumstantial evidence.

Dermatopathology Case 72


Case 72

Spot diagnosis

Monday, September 27, 2010

Answer of Dermatopathology Case 71

Grover's Disease

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Photo Quiz-Pruritic Papules on the Chest and Back:Am Fam Physician. 2006 Aug 15;74(4):641-642.

Grover's disease: clinicopathologic review of 72 cases. Mayo Clin Proc. 1999 Mar;74(3):229-34.

OBJECTIVE: To report the clinicopathologic findings in patients with Grover's disease.
MATERIAL AND METHODS: We reviewed the medical records and biopsy specimens from 72 patients with transient acantholytic dermatosis (Grover's disease) examined at Mayo Clinic Rochester. Hematoxylin-eosin-stained biopsy specimens (from all patients) were assessed. Immunohistochemistry stains BRST-2, CAM 5.2, and CD44 were used to stain eight specimens. Direct immunofluorescence reports were reviewed. Selected specimens were stained by indirect immunofluorescence to detect major basic protein.
RESULTS: Of the 72 patients, 63 (88%) were men, and the mean age was 48 years (range, 31 to 85). Lesions were distributed mainly on the trunk (in 71 patients) and proximal extremities (in 25). Heat and sweating frequently were exacerbating factors. Fifteen patients (21%) were bedbound. Concurrent nondermatologic malignant disease was present in 18 patients (25%). Two patients (3%) had acquired immunodeficiency syndrome. Follow-up in 28 patients (mean, 38 months; range, 3 months to 7 years) revealed that the disease had recurred in 13, persisted in 3, and resolved in 12. Review of the biopsy specimens showed that acantholysis was pemphigus vulgaris-like in 40 patients (56%), Darier's disease-like in 16 (22%), spongiotic in 12 (17%), pemphigus foliaceus-like in 2 (3%), and Hailey-Hailey disease-like in 2 (3%). A perivascular lymphocytic infiltrate of varied intensity in 64 specimens (89%) was associated with eosinophils in 16 (22%). In nine biopsy specimens with dermal eosinophilia stained for major basic protein, varied dermal cellular and extracellular deposition of major basic protein was present. Results of direct immunofluorescence studies, performed in 17 cases, were negative or nonspecific. CD44 stained acantholytic areas in addition to sweat glands in two of eight specimens (25%).
CONCLUSION: Further studies of the pathogenesis of Grover's disease are needed. The predisposing conditions, site of involvement, and relapsing nature of this disorder may implicate acrosyringeal dysfunction as the cause.

Grover's disease: 34 years on.Australas J Dermatol.2004 ;45(2):83-6;quiz 87-8.

Grover's disease is an entity reported worldwide and recognized as a common disease since Grover first described it in 1970. Its cause remains obscure, but hospitalized, febrile and sun-damaged patients are particularly prone. It is frequently associated with some other skin diseases, including eczemas, psoriasis and solar keratoses. Acantholysis is the universal histological finding in all the varying clinical presentations. Treatment in the past has been ad hoc, but topical therapy, acitretin and phototherapy can suppress symptoms.

Transient acantholytic dermatosis (Grover's disease) in a renal transplant patient.J Dermatol. 2006 Mar;33(3):178-81.

Grover's disease ("transient acantholytic dermatosis") is a transient dermatosis of unknown cause manifesting clinically as a papular skin eruption located usually on the anterior chest and abdomen and histologically with dyskeratosis and acantholysis. Grover's disease has occasionally been reported in patients with chronic renal failure, HIV infection, hematological malignancies and bone-marrow allotransplantation. We report herein a new case of Grover's disease that developed in a renal transplant patient. To the best of our knowledge, this is the first observation of Grover's disease developing in the setting of solid organ transplantation.

Dermatopathology Case 71


Case 71

A 65 year old man with small, pruritic, erythematous papulovesicles on the upper arm. The patient had persistent fever and sweating. He also had a history of bone marrow transplantation.


Monday, September 6, 2010

Answer of Dermatopathology Case 70

Special stain: von Kossa stain


Perianal cutaneous malakoplakia in an immunocompetent patient. Dermatol Online J. 2010 Jan 15;16(1):10.
Malakoplakia is an uncommon inflammatory condition usually affecting the genitourinary tract, which has been associated with infections, tumors, and immunocompromised states. The condition has been reported in many different organs and it may rarely involve the skin. We describe a case of an isolated perianal cutaneous malakoplakia in an immunocompetent 23-year-old Syrian male.

[Vesico-cutaneous fistula revealing abdominal wall malakoplakia accompanied by Boeck's sarcoidosis]Orv Hetil.2010 Feb 7;151(6):220-3.
Malakoplakia is an acquired granulomatous disorder first described by Michaelis and Gutmann in 1902. The pathogenesis of malakoplakia is hardly known, but it thought to be secondary to an acquired bactericidal defect in macrophages occurring mostly in immunosuppressed patients.
CASE REPORT: 63-year-old female patient had been treated with methylprednisolone for ten years, because of pulmonary sarcoidosis. For six month, recurrent abdominal abscess and vesico-cutaneous fistula developed. Histological examination proved malakoplakia, and Escherichia coli was detected in the abscess cavity.
METHODS: Hematoxyline eosin staining, periodic acid-Schiff, Berlin-blue and Kossa reactions were performed.
RESULTS: Microscopically malakoplakia consists of mainly macrophages, known as von Hansemann cells with scattered targetoid intracytoplasmic inclusions known as Michaelis-Gutmann bodies. In our presented case, after urological-surgical intervention and antibiotic therapy, the patient became free from complaints and symptoms.
DISCUSSION: Malakoplakia has been described in numerous anatomic locations, mainly in the urogenital tract. Malakoplakia may be complicated with fistulas in different locations: vesico-coccygeal, rectoprostatic, anorectal fistulas have been were reported in the literature, while 6 cases of malakoplakia with Boeck's sarcoidosis are published.
CONCLUSION: In the presented case sarcoidosis and the 10-year immunosuppressive treatment with methylprednisolone might have been in the background of abdominal wall malakoplakia, complicated by vesico-cutaneous fistula. The patient was successfully treated with surgery and the followed antibiotic therapy.

Cutaneous malakoplakia.Arch Pathol Lab Med. 2008 Jan;132(1):113-7.
Malakoplakia is an acquired granulomatous disorder first described by Michaelis and Gutmann in 1902. The pathogenesis of malakoplakia is poorly understood, but it is thought to be secondary to an acquired bacteriocidal defect in macrophages occurring mostly in immunosuppressed patients or in the setting of autoimmune disease. Malakoplakia has been described in numerous anatomic locations, most commonly in the genitourinary tract. Microscopically, malakoplakia consists predominantly of sheets of macrophages known as von Hansemann cells with scattered targetoid intracytoplasmic inclusions known as Michaelis-Gutmann bodies. Cutaneous malakoplakia is a rare entity with less than 50 cases reported in the literature. In this article, we review cutaneous malakoplakia including the clinical, gross, and microscopic features as well as the treatment and prognosis of 40 cases of cutaneous malakoplakia identified in the literature.

Cutaneous malakoplakia in an HIV-positive patient.Int J STD AIDS.2007 Jun;18(6):435-6.
Malakoplakia is an uncommon granulomatous infectious disease that is found primarily in the genitourinary tract, but may rarely involve the skin. We report a case of cutaneous malakoplakia in an HIV-positive patient diagnosed on the basis of Michaelis-Gutman bodies. The patient presented with ulcers, draining sinuses and tender papules and nodules mainly on perigenital area, buttocks and right thigh.

Cutaneous malakoplakia: a report of two cases with the use of anti-BCG for the detection for micro-organisms. J Am Acad Dermatol.2000 Aug;43(2 Pt 2):351-4.
Malakoplakia is an uncommon granulomatous infectious disease that is found primarily in the genito-urinary tract, but may rarely involve the skin. Histologic findings are marked by the presence of foamy macrophages containing basophilic concentric spherules, the Michaelis-Gutman bodies. Micro-organisms are not readily identifiable. Immunostaining with polyclonal anti-mycobacterium bovis (BCG) has been described as a method of identifying bacterial and fungal organisms in situations where organisms may be sparse. We report 2 cases of cutaneous malakoplakia with demonstration of organisms by immunostaining with anti-BCG antibodies.

Dermatopathology Case 70

Image3 Special stain: PAS

Case 70

A 35 yr old immunosuppressed patient with a polypoid mass in the perianal region.

Sunday, September 5, 2010

Answer of Dermatopathology Case 69

Dermatophyte Infection (Dermatophytoses) - Superficial filamentous Infection (Tinea - ringworm)

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Current knowledge of host response in human tinea.Mycoses.2009 Jan 21.
Summary Skin infection caused by dermatophytes is called tinea. In this short review, the known mechanisms and factors involved in human tinea and important for the host response are briefly delineated. To establish tinea, fungal propagules must attach to the skin, germinate and overcome the epidermal barrier. Keratinases and other enzymes are released in this process and host keratinocytes are activated. This is followed by an inflammatory response mediated by a plentitude of cytokines and receptors, comprising innate as well as acquired immunity, including neutrophilic granulocytes, macrophages, antibodies and T cells. Cellular defence mechanisms appear to be decisive for clearing of infection. Nails and hair follicles are the particular sites often invaded by dermatophytes that show distinctive patterns of infection. Nails are largely excluded from defence mechanisms and steroid hormones of the pilosebaceous units may have a particular effect on follicular infection. Fungal invasion of the dermis can cause granulomatous reactions. Immune reactions to dermatophytes may lead to sterile eruptions distant from the infected skin areas.

Pathogenesis of dermatophytosis and tinea versicolor. Clin Dermatol. 2010 Mar 4;28(2):185-9.
Dermatophytoses are infections caused by keratinophilic fungi known as dermatophytes. Several steps are required for infection to take place: contact, adherence, and invasion of keratin layers. The severity of the infection depends on the type of agent, environmental factors, and the host immunologic status. Tinea versicolor is caused by the Malassezia spp yeasts, which are microorganisms that belong to normal biota in seborrheic areas, but some contributing factors, such as the application of oily preparations, creams, an increase in ambient humidity, corticosteroid abuse, or genetic predisposition can induce its overgrowth in both filamentous and yeast structures. Exposure to sunlight stimulates the production of azelaic acid, which causes the appearance of hypopigmented spots. Currently, there is no scientific explanation for hyperpigmented lesions.

Evaluation of a modified microscopic direct diagnosis of dermatophytosis. J Microbiol Methods. 2010 May;81(2):205-7. Epub 2010 Mar 6.
Here we present a modified protocol for dematophyte diagnosis, utilizing a simple centrifugation step to significantly decrease false-negative results of the original KOH direct microscopy-based technique. Although culture constitutes the gold-standard diagnosis, the time spent for results is a limit. Fast and low-cost techniques are important for infection screening in underdeveloped countries.

The dermatophytes. Clin Microbiol Rev.1995 Apr;8(2):240-59.
The etiologic agents of the dermatophytoses (ringworm) are classified in three anamorphic (asexual or imperfect) genera, Epidermophyton, Microsporum, and Trichophyton. Species capable of reproducing sexually belong in the teleomorphic genus, Arthroderma, of the Ascomycota. On the basis of primary habitat association, they may be grouped as geophilic (soil associated), zoophilic, and anthropophilic. Adaptation to growth on humans by most geophilic species resulted in diminished loss of sporulation, sexuality, and other soil-associated characteristics. The dermatophytes have the ability to invade keratinized tissue (skin, hair, and nails) but are usually restricted to the nonliving cornified layer of the epidermis because of their inability to penetrate viable tissue of an immunocompetent host. However, invasion does elicit a host response ranging from mild to severe. Acid proteinases, elastase, keratinases, and other proteinases reportedly act as virulence factors. The development of cell-mediated immunity correlated with delayed hypersensitivity and an inflammatory response is associated with clinical cure, whereas the lack of or a defective cell-mediated immunity predisposes the host to chronic or recurrent dermatophyte infection. Chronic dermatophytosis is mostly caused by Trichophyton rubrum, and there is some evidence that mannan produced by this fungus suppresses or diminishes the inflammatory response. Since dermatophytes cause a communicable disease, modes of transmission and control are discussed as well as a survey of recent trends in therapy. Collection of specimens, culture media, and tests for identification are also presented. Genetic studies have led to an understanding of incompatibility mechanisms, pleomorphism and variation, resistance to griseofulvin, and virulence. Molecular biology has contributed to our knowledge of the taxonomy and phylogenetic relationships of dermatophytes.

Dermatopathology Case 69

Image 1
Image3 (Special stain-PAS)
Image4 (Special stain - Grocott)

Case 69

Spot Diagnosis


Answer of Dermatopathology Case 68


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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.

Scabies.Dermatol Ther.2009 Jul-Aug;22(4):279-92.
Scabies is an ectoparasite caused by the mite Sarcoptes scabiei var hominis, an obligate human parasite. There are about 300 million cases of scabies in the world each year. Common predisposing factors are overcrowding, immigration, poor hygiene, poor nutritional status, homelessness, dementia, and sexual contact. Direct skin-to-skin contact between 15 and 20 minutes is needed to transfer the mites from one person to another. The diagnosis suspected with a clinical history of itch, worse at night, affecting other family members, clinical distribution, and appearance. Definite diagnosis relies on microscopic identification of the mites, eggs, or fecal pellets with 10% potassium hydroxide, ink enhancement, tetracycline fluorescence tests, or mineral oil; other methods include: epiluminescence light microscopy and S. scabiei DNA. The most commonly used treatment modalities are permethrin and ivermectin. Persistence of symptoms for 2-6 weeks after successful treatment is common. Most recurrences are because of reinfection from untreated contacts.

Crusted (Norwegian) scabies following systemic and topical corticosteroid therapy.J Korean Med Sci.2010 Jan;25(1):188-91. Epub 2009 Dec 26.
It is a case study of a 62-yr-old female with crusted (Norwegian) scabies, which appeared during her treatment with systemic and topical corticosteroid therapy, under the diagnosis of erythroderma. In the same time, the patient had been suffered from hypothyoidism, and her skin changes were misdiagnosed, because it was thought that they are associated with her endocrine disorder. Suddenly, beside the erythema, her skin became hyperkeratotic, with widespread scaling over the trunk and limbs, and crusted lesions appeared on her scalp and ears. The microscopic examination of the skin scales with potassium hydroxide demonstrated numerous scabies mites and eggs. Repeated topical treatments with lindan, benzoyl benzoat and 10% precipitated sulphur ointment led to the complete resolution of her skin condition.

Diagnostic dilemma: crusted scabies superimposed on psoriatic erythroderma in a patient with acquired immunodeficiency syndrome. Skinmed.2007 May-Jun;6(3):142-4.
A 45-year-old man with AIDS presented with extensive erythema and scaling involving the face, trunk, and upper and lower extremities, and mild nail dystrophy. The patient had been diagnosed with psoriasis 2 years previously, and at the time of presentation was using emollients and topical corticosteroid creams with little improvement. He was receiving zidovudine, lamivudine, trimethoprim/sulfamethoxazole, acyclovir, rifabutin, and hydroxyzine. Pertinent laboratory data included CD4 lymphocytes (10 cells/mm(3)), viral load (32,000 copies per mL) white blood cell count (3.4 x 10(3)/microL), hemoglobin (13.5 g/dL), and platelets (204 x 10(3)/microL). Because of the extensive eruption and lack of response to topical agents, the patient was started on acitretin 25 mg daily. The patient had shown no signs of improvement 4 weeks later and was noted to have brownish gray crusted plaques involving the beard area, neck, upper part of the back, arms, trunk, genitals, and thighs in addition to his erythroderma (Figure 1 and Figure 2). Microscopic examination of scales from the upper part of the back revealed numerous scabies mites and eggs. He was then treated with lindane shampoo on the scalp and beard area and permethrin 5% cream to the body. The patient returned 2 weeks later with some improvement after thrice-weekly applications of this regimen; however, scrapings from the trunk once again revealed live scabies mites. Microscopic examination of scales that had fallen on the examination table revealed multiple mites and eggs. The patient was then given permethrin 5% cream, which he applied 3 times a week for 2 weeks, and 1 dose of oral ivermectin, 200 micro/kg. This resulted in a marked decrease in crusting and scaling. With resolution of the scabies lesions, the patient displayed marked erythema and scaling of the trunk and extremities consistent with generalized psoriasis (Figure 3). Treatment with acitretin resulted in gradual resolution of the erythroderma. A few months later, the patient presented with nodules on the upper part of the back, which on biopsy revealed a scabies mite (Figure 4).

Diagnosis and treatment of scabies: a practical guide. Am J Clin Dermatol.2002;3(1):9-18.
Scabies is a common, highly pruritic infestation of the skin caused by Sarcoptes scabiei var. Hominis. It is a very contagious parasitosis with specific lesions, such as burrows, and nonspecific lesions, such as papules, vesicles and excoriations. The typical areas of the body it affects are finger webs, wrists, axillary folds, abdomen, buttocks, inframammary folds and, in men, the genitalia. It is characterized by intense nocturnal pruritus. Scabies is spread through close personal contact (relatives, sexual partners, schoolchildren, chronically ill patients and crowded communities). Definitive diagnosis is made when the scabies mites or their eggs or fecal pellets can be identified on a light microscope. New techniques for diagnosis include the use of the epiluminiscence microscopy. The most common topical treatments for scabies include lindane and permethrin. Permethrin provides a greater margin of tolerability because of its low inherent toxicity and low percutaneous absorption. Oral ivermectin is the most recently developed treatment for scabies. A single oral dose of ivermectin 200 microg/kg of bodyweight is a well-tolerated and very effective treatment. It is especially indicated in crusted scabies, scabies in immunocompromised hosts and infestations in crowded communities. It is also useful as a simple treatment in the prophylaxis of close contacts.

Dermatopathology Case 68

Image4 Section of the superficial dermis

Case 68

Intensely pruritic papules in the inframammary region of a 35 year old woman. Spot diagnosis!

Thursday, September 2, 2010

Answer of Dermatopathology Case 67

Special stain: Congo red

Lichen Amyloidosus

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Lichen amyloidosis in a dark skinned patient.G Ital Dermatol Venereol. 2010 Feb;145(1):135-8.
Lichen amyloidosis is a primary localized cutaneous amyloidosis without systemic involvement, characterized by a persistent pruritic eruption of multiple discrete hyperkeratotic papules. The etiology is unknown, but chronic irritation of the skin has been proposed as an etiological factor. We herein report a typical case of lichen amyloidosis in a dark skinned patient. Physical examination revealed slightly shiny, brownish and fine uniform papules approximately 1 cm in diameter, with no accompanying macular lesions. Biopsy specimens taken from some of these papules on the legs showed small globular deposits of an amorphous and slightly eosinophilic substance in the dermis. This substance stained positively with Congo red, indicating the presence of amyloid. In addition, amyloid gave an apple green birefringence when viewed with polarized light.

New insight into mechanisms of pruritus from molecular studies on familial primary localized cutaneous amyloidosis. Br J Dermatol.2009 Dec;161(6):1217-24. Epub 2009 May 26.
Macular and lichen amyloidosis are common variants of primary localized cutaneous amyloidosis (PLCA) in which clinical features of pruritus and skin scratching are associated with histological findings of deposits of amyloid staining on keratinous debris in the papillary dermis. Most cases are sporadic, but an autosomal dominant family history may be present in up to 10% of cases, consistent with a genetic predisposition in some individuals. Familial PLCA has been mapped to a locus on 5p13.1-q11.2 and in 2008 pathogenic heterozygous missense mutations were identified in the OSMR gene, which encodes oncostatin M receptor beta (OSMRbeta), an interleukin (IL)-6 family cytokine receptor. OSMRbeta is expressed in various cell types, including keratinocytes, cutaneous nerves and nociceptive neurones in dorsal root ganglia; its ligands are oncostatin M and IL-31. All pathogenic mutations are clustered in the fibronectin-III repeat domains of the extracellular part of OSMRbeta, sites that are critical for receptor dimerization (with either gp130 or IL-31RA), and lead to defective signalling through Janus kinase-signal transducers and activators of transcription, extracellular signal-regulated protein kinase 1/2 and phosphoinositide 3 kinase/Akt pathways. Elucidating the molecular pathology of familial PLCA provides new insight into mechanisms of pruritus in human skin, findings that may have relevance to developing novel treatments for skin itching. This review provides a
clinicopathological and molecular update on familial PLCA.

Familial primary localized cutaneous amyloidosis in Brazil.Arch Dermatol.2009; 145(6):695-9.
BACKGROUND: Macular and lichen amyloidosis are clinical variants of primary localized cutaneous amyloidosis (PLCA). Most cases are sporadic, but approximately 10% of cases may be familial. To our knowledge, the clinicopathologic and molecular features of such pedigrees, however, have not been studied in detail.
OBSERVATIONS: We assessed 2 Brazilian families with either lichen-type (family 1 had 14 affected subjects) or macular-type (family 2 had 7 affected subjects) PLCA. Typically, in both pedigrees, the onset of symptoms was around puberty, and pruritus usually began on the lower legs. Findings from lesional skin biopsy samples from both families showed thioflavin T-positive material in the papillary dermis, which was more prominent in the lichen phenotype in family 1. Spontaneous improvement occurred in 3 subjects (from both families) after age 25 years. All affected individuals in family 1 had a heterozygous missense mutation in the OSMR gene (p.I691T), but no pathogenic mutation in OSMR was found in family 2.
CONCLUSIONS: Familial PLCA shows autosomal dominant inheritance, but there is clinical and genetic heterogeneity and variable clinical penetrance. Demonstration of mutations in the OSMR gene provides new insight into mechanisms of itch and apoptosis in human skin.

Familial medullary thyroid carcinoma associated with cutaneous lichen amyloidosis. Thyroid.2009 Jun;19(6):651-5.
BACKGROUND: This is a report of a patient with a novel genotype-phenotype relationship of a c804 mutation of the RET proto-oncogene manifesting as medullary thyroid carcinoma (MTC) and cutaneous lichen amyloidosis (CLA).
SUMMARY: Clinical data were obtained for patient appearance and laboratory results. Analyzed were histopathology of the skin lesion and thyroid gland, genetic mutation, and family pedigree. Skin histology and histochemistry were consistent with CLA. Serum calcitonin levels were moderately elevated. Thyroid histology demonstrated a 4 mm focus of MTC. Measurements of serum parathormone, calcium, and plasma metanephrines were normal. DNA analysis demonstrated a mutation in codon 804 of the RET proto-oncogene resulting in a Valine to Methionine (V804M) substitution. Genetic testing in two siblings revealed the same mutation.
CONCLUSIONS: This is the first description of a patient with CLA not associated with a mutation in codon 634. The patient is one of the few with a V804M mutation in whom the clinical expression did not fully conform to the definition of familial MTC.

Lichen amyloidosis induced on the upper back by long-term friction with a nylon towel.J Dermatol.2009 Jan;36(1):56-9.
Primary localized cutaneous amyloidosis can take several clinical forms. In Asia, macular amyloidosis caused by prolonged friction from a rough nylon towel or brush is common, and macular amyloidosis and lichen amyloidosis occasionally occur together, as so-called biphasic amyloidosis. We report herein the case of an 83-year-old Japanese man with lichen amyloidosis caused by prolonged nylon towel friction. This patient presented with unique symmetrical papular lesions on the upper back and shoulders. Lesions comprised slightly shiny, brownish, fine uniform papules approximately 0.5 mm in diameter, showing a partially linear, annular or rippled arrangement. Although this case was caused by prolonged nylon towel friction, no coexisting macular lesions could be found. To the best of our knowledge, this represents the first case of lichen amyloidosis induced by nylon towel friction in the absence of the macular amyloidosis that is usually observed in such cases. We instructed the patient to stop the habit of nylon towel rubbing and prescribed a topical steroid ointment and cepharanthine. After 6 months of treatment, papular lesions became clearly flatter.

Dermatopathology Case 67


Case 67

A 48 yr old male with pruritic, waxy papules on the extensor surface of the left lower limb.

Wednesday, September 1, 2010

Answer of Dermatopathology Case 66

Melanocytic Nevus of the Vulva (Site specific nevus)

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Precursors to melanoma and their mimics: nevi of special sites.Mod Pathol.2006 Feb;19 Suppl 2:S4-20.
Melanocytic nevi, which are benign tumors of melanocytes, may have occasional cosmetic significance but, for the most part, they are important only in relation to melanoma. Nevi are the most important simulants of melanoma, both clinically and histologically, and can usually be reliably distinguished from melanomas using published criteria. Some lesions are characterized by greater degrees of atypia and may be more difficult to diagnose. Dysplastic nevi are among the most important simulants of melanoma. Nevi may also be important as potential precursors of melanoma; however, most nevi are stable and will not progress to malignancy. Nevi are vastly more common than melanomas and the rate of progression of individual lesions is very low. Therefore, nevi are not as a rule managed by wholesale excision to prevent melanoma. Nevi are also important as risk markers, identifying individuals at greater risk of developing melanoma in the future. Dysplastic nevi and, to a lesser extent, common acquired and congenital nevi are among the most important melanoma risk markers. Nevi of special sites have been identified as nevi that may show atypical features suggestive of a dysplastic nevus or of a melanoma. However, they are not risk markers and they are not malignancies. Nevi of genital skin, acral skin, and flexural skin are among the most important 'nevi of special sites'. It is important, in considering the differential diagnosis of a lesion in a special site, to avoid overcalling such a lesion as a melanoma or a dysplastic nevus because this could lead to excessive treatment. Conversely, it is important to avoid undercalling a lesion that is a dysplastic nevus or a melanoma as a nevus of special sites, because in this circumstance a patient could lose the opportunity either for surveillance to recognize a developing melanoma at an early, curable stage, or for definitive treatment of an established malignancy. In this monograph, dysplastic nevi and nevi of special sites are compared and contrasted in relation to melanoma.

Nevi with site-related atypia: a review of melanocytic nevi with atypical histologic features based on anatomic site.J Cutan Pathol. 2008 Oct;35(10):889-98.

A subset of melanocytic nevi share features with melanoma and nevi with architectural disorder but are biologically inert and to date do not appear to portend an increased risk for the development of malignancy. These benign nevi with certain atypical histologic features cluster among specific anatomic sites and are thus designated nevi with site-related atypia. We categorize these lesions into four main groups: acral, genital, special site and conjunctival, based on anatomy and relative prevalence of specific atypical histologic features. As the literature and our recognition of these lesions continue to grow, our understanding of their biology has not kept pace.

Melanocytic lesions of the genital area with attention given to atypical genital nevi.J Cutan Pathol. 2008 Nov;35 Suppl 2:24-7.

Melanocytic lesions of the genital area are rare. They arise mainly in the vulva, although they can also occur less frequently in the perineum, mons pubis and male genitalia and represent 10-12% of pigmented lesions of White women. These pigmented lesions include melanocytic nevi, lentigines, melanocytic nevi with architectural disorder and atypia of melanocytes (dysplastic nevi) and melanomas with microscopic features similar to those seen elsewhere on the body. There is a small subset of benign nevi named atypical melanocytic nevi of the genital type (AMNGT) that occur in young women, with distinctive histologic features in some cases overlapping morphologically with those of melanoma. Thus, it is important to distinguish AMNGT from melanomas in terms of prognosis and treatment. We retrieved 58 cases of genital pigmented lesions diagnosed at our hospital from 1986 to 2008 to evaluate their clinicopathologic features with especial consideration to those cases with atypical features. Thirty-two cases (55%) were common nevi, 10 (17%) lentigines, 6 (10%) melanomas, 3 (5%) dysplastic nevi and 1 blue nevus. Six cases (10%) corresponded to AMNGT and were taken from women with a median age of 21 years. All cases showed symmetry, and the melanocytic proliferation was well demarcated at the lateral margins. The junctional component was very prominent and formed by round or fusiform nests with common retraction artifact and/or cellular dyshesion or as a single cell proliferation with mild (33%) to moderate (67%) cytologic atypia, focal pagetoid spread (17%) and a benign-appearing dermal component (83%) with maturation and dense eosinophilic fibrosis in the superficial dermis. Neither nuclear atypia of melanocytes in the superficial dermis nor dermal mitoses were observed. AMNGT were excised, and no recurrences were recorded in the follow up (median 10.5 years). Therefore, it seems that there is no evidence that AMNGT are precursors of dysplastic nevi or melanomas.

Dermatopathology Case 66



Case 66

A vulval lesion in a 65 yr old female.


Answer of Dermatopathology Case 65

Trichilemmal Carcinoma

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Trichilemmal carcinoma of the upper eyelid: a case report.Korean J Ophthalmol.
2009 Dec;23(4):301-5. Epub 2009 Dec 4.
We report a very rare case of trichilemmal carcinoma (TLC) involving the upper eyelid. To the best of our knowledge, this is the first report of trichilemmal carcinoma of the upper eyelid in Korea. A 51-year-old man presented to our hospital complaining of a bloody discharge from his left upper eyelid. He had a soft and lobulated mass on the palpebral conjunctiva. An incisional biopsy revealed trabecular growth of tumor cells with clear cytoplasm, prominent nucleoli, frequent mitoses, and foci of trichilemmal keratinization. Immunohistochemically, the lesion was positive for p53 and negative for CD 34. A diagnosis of TLC was made, and total excision of the mass and reconstruction of the eyelid were performed. Trichilemmal carcinoma is a rare malignant tumor, though it appears to be an indolent neoplasm with no metastatic potential. The treatment of choice for trichilemmal carcinoma of the eyelid is complete excision with tumor-free margins due to the locally invasive nature of the lesion.

Trichilemmal carcinoma arising in seborrheic keratosis: a case report and published work review. J Dermatol.2008 Dec;35(12):782-5.
The secondary skin malignancies arising in seborrheic keratosis (SK) are uncommon, and the causal association between the pre-existing lesion and subsequent malignant transformation remains uncertain. Among these enigmatic conditions, trichilemmal differentiation and/or neoplasms in SK have rarely been reported thus far. Herein, we describe a case of invasive trichilemmal carcinoma arising in a long-standing SK of the abdominal skin, and clinicopathologically review this rare complication with a computerized medical published work search (PubMed) and citations from earlier reports. To our knowledge, only four cases of trichilemmal tumors arising in SK have been observed, and, interestingly, all cases, including ours, were Japanese. Four of five cases (80%) developed the tumors in non-sun-exposed SK, and indeed had no apparent actinic damage in the histology. The pre-existing SK itself is more likely to act as the primary pathogenic event for developing the secondary trichilemmal tumors than a coincidental phenomenon and a consequence of skin damage by cumulative sun exposure.

Trichilemmal carcinoma--a rare tumor: case report.Acta Dermatovenerol Croat. 2008;16(1):28-30.Acta Dermatovenerol Croat. 2008;16(1):28-30.
Trichilemmal carcinoma is a rare cutaneous cancer that usually occurs on photoexposed areas in elderly individuals. Most of the time, there is a unique lesion that presents a papulonodular aspect with possible keratosis or ulceration on the top of it. We report on a case of this rare tumor, discussing various aspects of this entity and possible therapy. Simple excision with adequate safety margin is a safe, low-cost and effective mode of treatment for this type of carcinoma. Although a rare form of neoplasia, trichilemmal carcinoma has good prognosis when treated correctly.

Trichilemmal carcinoma: a rare cutaneous malignancy: a report of two cases. Dermatol Surg. 2004 Jan;30(1):113-5.
BACKGROUND: Trichilemmal carcinoma is a rare cutaneous malignancy that usually occurs on the sun-exposed areas of older individuals. The lesion is usually solitary and may present as an exophytic or polypoid nodule that maybe hyperkeratotic with ulceration.
OBJECTIVE: To present two cases of trichilemmal carcinoma, one occurring in a kidney transplantation patient.
METHODS: Two case reports and a discussion of the rare carcinoma are presented.
RESULTS: Both lesions were treated with Mohs micrographic surgery without sign of recurrence after several years.
CONCLUSION: Trichilemmal carcinoma is a rare cutaneous malignancy that can be seen in both immunocompetent and immunosuppressed hosts. Mohs micrographic surgery should be considered among the surgical options to avoid a wide surgical excision in these patients.

Dermatopathology Case 65


Case 65
A solitary nodule on the left upper arm of a 78 yr old man.

Tuesday, August 31, 2010

Answer of Dermatopathology Case 64

Immunohistochemistry: CD34 is strongly positive.

Dermatofibrosarcoma Protuberans

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Cutaneous CD34+ Spindle Cell Neoplasms: Histopathologic Features Distinguish Spindle Cell Lipoma, Solitary Fibrous Tumor, and Dermatofibrosarcoma Protuberans.Am J Dermatopathol. 2010 Jun 17.
Spindle cell lipoma (SCL), dermatofibrosarcoma protuberans (DFSP), and solitary fibrous tumors (SFT) are cutaneous CD34+ spindle cell tumors that may exhibit histopathologic and immunophenotypic overlap. We sought ways to reliably distinguish among these lesions even in small or superficial biopsies. Ten morphologic characteristics were analyzed in a group of 5 SCLs, 6 cutaneous SFTs, and 12 DFSPs. SFT and DFSP exhibited extensive histopathologic overlap in small or partial biopsies. However, adnexal entrapment, defined as diffuse proliferation of tumor cells around pilosebaceous and eccrine structures with minimal disruption or expansion of the dermis, was a feature seen in 10 of the 12 DFSPs and in none of the SFTs or SCLs. Even when only superficial portions of a lesion were present, this feature was identifiable. Spindle cell lipomas posed little diagnostic difficulty, in part because excisional biopsies were performed in all cases of SCL. The number of samples included in the study is relatively small, in part due to the rarity of cutaneous solitary fibrous tumors. We conclude that careful attention to these histopathologic features enables reliable distinction among these tumors.

Dermatofibrosarcoma protuberans: how wide should we resect?Ann Surg Oncol. 2010 Aug;17(8):2112-8. Epub 2010 Mar 31.
BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare dermal tumor with local recurrence rates ranging from 0 to 50%. Controversy exists regarding margin width and excision techniques, with some advocating Mohs surgery and others wide excision (WE). We reviewed the experience in two tertiary centers using WE with total peripheral margin pathologic evaluation.MATERIALS AND METHODS: Institutional Review Board approved retrospective review of patients with DFSP from 1991 to 2008. Patients had initial WE using 1-2 cm margins with primary or delayed closure; further excision was done whenever feasible for positive margins. Pathologic analysis included en face sectioning. We evaluated margin width, number of WE, reconstruction methods, radiation, and outcomes.RESULTS: A total of 206 DFSP lesions in 204 patients (76 males, 128 females), median age 41 years (range 1-84) were treated. Locations were trunk (135), extremities (43), and head and neck (28). The median number of excisions to achieve negative margins was 1 (range 1-4) with a median excision width of 2 cm (range 0.5-3 cm). Closure techniques included primary closure (142; 69%), skin grafting (52; 25%), and tissue flaps (9; 4%). There were 9 patients who received postoperative radiation, 6 for positive margins after maximal surgical excision. At a median follow-up of 64 months (range 1-210), 2 patients (1%) with head and neck primaries recurred locally.CONCLUSIONS: Using a standardized surgical approach including meticulous pathologic evaluation of margins, a very low recurrence rate (1%) was achieved with relatively narrow margins (median 2 cm), allowing primary closure in 69% of patients. This approach spares the additional morbidity associated with wider resection margins and in our experience represents the treatment of choice for DFSP occurring on the trunk and extremities.

Dermatofibrosarcoma protuberans in the breast of a 2-year-old girl.Ann Diagn Pathol.2010 Aug;14(4):279-83. Epub 2009 Dec 1.
Dermatofibrosarcoma protuberans (DFSP) is a low-grade dermal and subcutaneous spindle cell neoplasm that most commonly occurs in the extremities and trunk of adults. It is rare in children and infants, and only few cases are reported as congenital. A 2-year-old girl presented with a rapidly enlarging left breast mass. The histology of the excised mass revealed a moderately cellular spindle cell tumor with large hypercellular fibrosarcoma-like areas, few myxoid areas, and other areas with multinucleated giant cells. By immunohistochemistry, the tumor cells were focally positive for CD34 and were negative in the fibrosarcomatous areas. The diagnosis of DFSP was confirmed by demonstrating an unbalanced translocation der(22)t(17;22)(q21.3;q13.1) by conventional cytogenetic and fluorescence in situ hybridization analyses. Positive immunoreactivity with PDGFR-beta antibody indicated constitutional activation of PDGF receptor and provided an alternate indirect method of confirming the presence of dysregulated PDGF gene involved in this translocation. Although DFSP has been described in the adult female breast, this is the first such case in the breast of a 2-year-old girl. Dermatofibrosarcoma protuberans should be considered in the differential diagnosis of subcutaneous/dermal spindle cell tumors in children regardless of the site. CD 34 immunostaining should not be relied on, as it may be negative in fibrosarcomatous areas. Confirmation of the diagnosis in unusual sites requires identification of the characteristic t(17;22) chromosomal translocation.

Dermatofibrosarcoma protuberans of the vulva: a clinicopathologic and immunohistochemical study of 13 cases. Am J Surg Pathol. 2010;34(3):393-400.
Dermatofibrosarcoma protuberans (DFSP) is a low-grade sarcoma seldom seen in the vulva with only 29 cases reported. We present the clinicopathologic and immunohistochemical features of 13 such cases seen in our institution over a period of 29 years (1978 to 2007). Patient age ranged from 23 to 76 years (mean, 46 y). Twelve patients had a vulvar mass. One patient presented with a pigmented skin lesion. Tumor size ranged from 1.2 to 15 cm (median, 4 cm). Microscopically, all the cases showed typical features of DFSP. In 1 case, myxoid changes were also noted; 3 cases showed fibrosarcomatous transformation. Of interest, in 7 of our 13 cases, a variety of diagnoses, such as cellular dermatofibroma, cellular leiomyoma, neurofibroma, low-grade leiomyosarcoma, fibrosarcoma, low-grade malignant schwannoma, desmoplastic melanoma, cellular neurofibroma, and low-grade malignant peripheral nerve sheet tumor were initially considered. All 11 cases tested for CD34 were positive, whereas 7/9 cases, 8/9 cases, and 9/9 cases were positive for PDGFR-alpha, PDGFR-beta, and c-abl, respectively. All patients were initially treated with excisional biopsy, wide local excision, or radical vulvectomy. Local recurrences occurred in 7 cases. One patient also developed distant metastases. All recurrences were treated surgically; 1 patient also received chemotherapy and radiotherapy and another received imatinib (Gleevec). Follow-up data ranging from 2 to 444 months was available for all patients. Nine patients had no evidence of disease, 2 patients were alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. DFSP affects women of a wide age range and has a propensity to recur locally. The frequent expression of PDGFR-alpha, PDGFR-beta, and c-abl in these cases agrees with the findings of other investigators and supports the use of imatinib (Gleevec) in cases that are recurrent or not amenable to surgery.

Plaque-like CD34-positive dermal fibroma ("medallion-like dermal dendrocyte hamartoma"): clinicopathologic, immunohistochemical, and molecular analysis of 5 cases emphasizing its distinction from superficial, plaque-like dermatofibrosarcoma protuberans.Am J Surg Pathol.2010 Feb;34(2):190-201.
We analyzed the clinical, histomorphologic, and molecular criteria of 5 DH and 7 DFSP to delineate diagnostically relevant differences between incipient dermal DFSP and its benign look-alike, DH. We expand the clinical and histologic spectrum of DH. As medallion-like dermal DH is neither of dermal dendrocyte lineage nor a genuine hamartoma, we propose instead the descriptive term of plaque-like CD34-positive dermal fibroma (PDF). Both PDF/DH and DFSP presented as slightly pigmented and indurated plaques on neck, trunk, and extremities. Histologically, DFSP was characterized either by horizontally oriented spindle cell fascicles or by diffusely arranged fibroblasts within a slightly myxoid stroma in the upper two-thirds of the dermis, whereas PDF/DH presented with a cellular band-like fibroblastic proliferation mostly in the papillary and adjacent upper reticular dermis. Only one congenital PDF/DH in a 9-year-old boy extended into the septa of the subcutaneous fat. Formalin-fixed paraffin-embedded archival tissue was used for detection of the COL1A1-PDGFB gene rearrangement by multiplex reverse transcription-polymerase chain reaction (RT-PCR) and by dual color fusion fluorescence in-situ hybridization (FISH). Archival blocs older than 4 years did not yield amplifiable RNA because of RNA degradation, whereas FISH analysis was feasible in all investigated cases. FISH analysis revealed COL1A1-PDGFB gene rearrangement in all DFSP cases (n=7), whereas RT-PCR could detect the COL1A1-PDGFB fusion transcript only in 1 DFSP. Two cases were negative. In 4 archival cases with storage between 4.5 and 12 years, RNA had been degraded making these cases unsuitable for RT-PCR. In PDF/DH, both RT-PCR and FISH analysis did not reveal any evidence of COL1A1-PDGFB gene rearrangement. We show that PDF/DH and superficial (plaque-like) DFSP, subtle clinicopathologic differences notwithstanding, are morphologic look-alikes that can be kept apart by molecular studies of the COL1A1-PDGFB gene fusion. For the detection of the COL1A1-PDGFB gene rearrangement in diagnostically difficult cases, RT-PCR and FISH analysis are reliable and helpful diagnostic tools. In archival formalin-fixed paraffin-embedded tissue, however, FISH analysis is more robust and exhibits a higher clinical sensitivity than RT-PCR.

Dermatopathology Case 64


Case 64

A slow growing solitary reddish nodule in a 55 year old male. The nodule is 5 cm in diameter and is located on the right upper arm.

Sunday, August 22, 2010

Answer of Dermatopathology Case 63

Cutaneous Sarcoidosis

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Sarcoidosis of the skin--a dermatological puzzle: important differential diagnostic aspects and guidelines for clinical and histopathological recognition. J Eur Acad Dermatol Venereol.2010 Feb;24(2):125-37. Epub 2009 Aug 17.
Sarcoidosis of the skin may have an extremely heterogeneous clinical presentation, so that the definitions of 'great imitator' and 'clinical chameleon' have long been used. There is, in fact, a large group of skin diseases that can enter the differential diagnosis with cutaneous sarcoid manifestations, either clinically or/and pathologically. As the clinical consequences and the prognosis of these groups of diseases are often very different, it is important to correctly plan the diagnostic workup. The diagnostic process in this case often presents a challenge as no single test is sufficiently specific, so that a certain diagnosis can be only made in the presence of a compatible clinical and radiographic picture, along with histopathological evidence of non-necrotizing, epithelioid cell granulomas, and exclusion of other potential aetiologies. For practical reasons, four main groups of skin conditions capable of mimicking sarcoidosis can be identified: (i) transmissible, infectious diseases; (ii) allergic and immunological manifestations of various aetiologies; (iii) granulomatous diseases of various aetiologies; and (iv) lymphomas and pseudolymphomas. The aim of this article is to describe the main clinical and histopathological findings of such disease entities, and to discuss the role of those features (morphological, pathological and laboratory) that can help distinguish them from sarcoidosis of the skin.

Cutaneous sarcoidosis.Semin Respir Crit Care Med. 2010 Aug;31(4):442-51. Epub 2010 Jul 27.
Sarcoidosis is a systemic disease with skin manifestations. Skin manifestations are classified as nonspecific if they are not characterized by granulomatous inflammation and specific if the lesions have granulomas histologically. Erythema nodosum is the most common nonspecific skin manifestation, and it portends a good prognosis. Specific skin lesions have a varied clinical appearance, although often they can be distinguished by their yellow translucent character. Despite the potential variable appearance, there are common clinical presentations. Lupus pernio lesions are nodular violaceous specific skin lesions found predominantly on the face associated with scarring and a poor prognosis. Treatment of cutaneous sarcoidosis is primarily done to avoid scarring and cosmetic disfigurement. Local and systemic corticosteroids are the mainstay of treatment for the disease. Corticosteroid-sparing agents used to manage the disease include antimalarials, methotrexate, and tetracycline antibiotics. Tumor necrosis factor-alpha (TNF-alpha) antagonists such as infliximab may have a role in cutaneous sarcoidosis, especially in refractory cases that are resistant to the standard regimens.

Cutaneous sarcoidosis presenting as multiple erythematous macules and patches.Ann Dermatol. 2009 May;21(2):168-70. Epub 2009 May 31.
Sarcoidosis is an idiopathic multisystemic disorder with variable cutaneous presentations that are classified as specific or non-specific according to the presence of non-caseating granulomas on histologic examination. Specific manifestations can include papules, scar sarcoidosis, ulcers, or even alopecia. Herein, we present a case of cutaneous sarcoidosis that presented as multiple erythematous macules and patches on the trunk and extremities of a 32-year-old man. The clinical appearance was unlike any other form reported in the literature.

Cutaneous sarcoidosis: the "great imitator": etiopathogenesis, morphology, differential diagnosis, and clinical management.Am J Clin Dermatol.2006;7(6):375-82.
Sarcoidosis is a multisystem disease that can involve almost any organ system. The underlying cause of the disease remains unknown. Immunopathologically and histologically, cutaneous sarcoidosis is characterized by a macrophage/T helper-1 cell-mediated, non-caseating, granulomatous inflammation process. An imbalance between proinflammatory and anti-inflammatory cytokines plays an important role in the development of cutaneous granulomas. Recognition of cutaneous sarcoidosis lesions is very important because they provide a visible clue to the diagnosis and are an easily accessible source of tissue for histologic examination. Because skin lesions of patients with the disease can exhibit many different morphologies, cutaneous sarcoidosis is known as one of the "great imitators" in dermatology. Specific manifestations can include patches (sometimes hypopigmented), papules, scar sarcoidosis, ulcers, ichthyosis, and alopecia. The treatment of cutaneous sarcoidosis is often frustrating because some of the skin lesions may be refractory to treatment or may recur following successful treatment. Systemic and topical corticosteroids are the most effective treatments for cutaneous sarcoidosis. This article focuses on the dermatologic aspects of sarcoidosis and includes a review of the most recent literature, which includes new data on the diagnosis, differential diagnosis, pathogenesis, and treatment of the disease.

Dermatopathology Case 63

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Case 63

A 35 year old male with maculopapular eruption. Patient also has history of acute lymphadenopathy and uveitis.

Answer of Dermatopathology Case 62

Chondroid Syringoma

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Chondroid syringoma: a rare tumor of the chest wall. Ann Thorac Surg.2010 Mar;89(3):983-5.

Chondroid syringoma, an uncommon, slow-growing, benign, sweat-gland tumor located on the upper right chest wall of a 66-year-old woman is presented. This skin adenexal tumor is typically located on the head and neck region. The unusual location of chondroid syringoma made an accurate preoperative diagnosis difficult, and diagnosis was achieved only by excisional biopsy and histopathologic examination. Total surgical excision remains the best therapeutic option to avoid tumor recurrence and close follow-up is recommended because of a rare possibility of malignant transformation and visceral metastases.

Chondroid syringoma of the hand.Scand J Plast Reconstr Surg Hand Surg.2009;43(5):291-3.

Chondroid syringoma is a rare cutaneous tumour that usually arises in the head and neck region and is rarely seen on the hands; it is rarely malignant at sites other than the head and neck. However, it should be included in the differential diagnosis of tumours of the hand. We present a 56-year-old man with a chondroid syringoma of the hand that clinically resembled a vascular tumour.

Chondroid syringoma with tyrosine crystals: case report and review of the literature.Am J Dermatopathol.2010;32(2):171-4.

Chondroid syringoma (CS) is a relatively rare cutaneous mixed tumor arising from sweat glands. It usually presents in the head and neck area as an asymptomatic, slow-growing, firm, circumscribed, lobulated nodule within the dermis or subcutaneous fat. CSs share morphologic similarities with their salivary gland counterparts, pleomorphic adenomas (benign mixed tumors). Although the presence of tyrosine-rich crystalloids in mixed tumors of the salivary gland is well recognized, to our knowledge, this finding has not been previously described in mixed tumors of the skin. We report a case of tyrosine crystalline structures in a CS and review the pertinent literature.

Apocrine mixed tumor of the skin ("mixed tumor of the folliculosebaceous-apocrine complex"). Spectrum of differentiations and metaplastic changes in the epithelial, myoepithelial, and stromal components based on a histopathologic study of 244 cases.J Am Acad Dermatol.2007 Sep;57(3):467-83.

BACKGROUND: A systematic analysis of the entire spectrum of various forms of differentiation and metaplastic epiphenomena in cutaneous apocrine mixed tumor (AMT) has never been performed.
OBJECTIVE: The purpose of our study was to study a large number of cutaneous mixed tumors so as to fully characterize the entire spectrum of differentiations and metaplastic changes that may occur in the epithelial, myoepithelial, and stromal components of AMT.
METHODS: This article reports a light-microscopic study of 244 cases of cutaneous AMT, complemented by a literature review.
RESULTS: All types of differentiation along the lines of the folliculosebaceous-apocrine unit can be seen in AMT. The spectrum of metaplastic changes in the epithelial components includes squamous metaplasia, mucinous metaplasia, oxyphilic metaplasia, clear cell change, columnar metaplasia, hobnail metaplasia, and cytoplasmic vacuolization. The following changes in the myoepithelial component were documented: clear cell change, hyaline cells, plasmacytoid cells, spindling, and collagenous spherulosis. Stromal alterations included chondroid metaplasia, osseous metaplasia, and adipose metaplasia.
LIMITATIONS: This study utilizes tissue specimens that mainly came as consultations; therefore some inherent selection bias exists.
CONCLUSIONS: AMT displays a wide range of differentiation and metaplastic changes in its epithelial, myoepithelial, and stromal components. These phenomena are not mutually exclusive. When unduly prominent, they may present diagnostic pitfalls. Our findings corroborate those of previous publications, stressing the remarkable diversity of differentiation and metaplasias that may be found in cutaneous AMT. We propose that the most appropriate name for these lesions is "mixed tumor of the folliculosebaceous-apocrine complex."

Chondroid syringoma: case report and review of the literature.Dermatol Online J.2006 Sep 8;12(5):8.

An 84-year-old man presented with an enlarging bluish, painless subcutaneous nodule on the glabella. The lesion had been excised 4 years prior and was diagnosed as chondroid syringoma, but had gradually regrown. The recurrent lesion was treated by surgical re-excision. Histopathological examination was again consistent with chondroid syringoma, and showed the following: 1) a chondroid matrix, 2) tubuloalveolar structures lined by a double epithelium, 3) ductal structures lined by a single epithelium, 4) nests of polygonal cells, and 5) the presence of keratinous cysts. Chondroid syringoma is a rare mixed tumor of the skin that was first described by Hirsch and Helwig. Characteristically, it is composed of a proliferation of epithelial cells set in a myxoid and chondroid matrix. Although chondroid syringomas are predominantly benign, malignant forms have been reported.