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.








Wednesday, February 16, 2011

Answer of Dermatopathology Case 97

Immunohistochemistry findings:

CD3
CD4


Abstract:

Follicular mucinosis: a clinicopathologic, histochemical, immunohistochemical and molecular study comparing the primary benign form and the mycosis fungoides- associated follicular mucinosis.J Cutan Pathol. 2009 Jul 14.
Objectives: To determine (i) whether primary (idiopathic) follicular mucinosis (PFM) and lymphoma-associated follicular mucinosis (LAFM) are distinct or related entities and whether there are reliable criteria that allow the two forms to be distinguished, (ii) the histochemical properties and consequently the type of mucin that accumulates in the follicle in PFM and LAFM, and (iii) whether there is any difference between the staining properties of mucin in patients with PFM and LAFM. Methods: Thirty-one patients were divided into two groups. Group 1 comprised 20 patients with no associated mycosis fungoides or Sézary syndrome (PFM) and group 2 was made up of the other 11 patients who had clinicopathological evidence of cutaneous T-cell lymphoma (LAFM). The biopsy specimens of the patients were studied with histopathological, histochemical and immunohistochemical methods. Molecular biology studies were also performed. Results: Patients with PFM were more frequently younger (mean age 39 years), women (F:M=3:1), and presented with a solitary lesion involving the head/neck area more often than patients with LAFM who were older (mean age 54 years), men (M:F=2:1), and presented with multiple lesions on areas of the body other than the head/neck area. As for histopathological findings, large cystic spaces filled with mucin and a slight perivascular and periadnexal polyclonal infiltrate of mostly non-atypical lymphocytes without epidermotropism and with an equivalent CD4+/CD8+ cell rate were more suggestive of PFM. On the contrary, patients with LAFM were more probably to present with a dense band-like infiltrate with some atypical lymphocytes and sign of epidermotropism, a prominent CD4+ immunophenotype and a monoclonal rearrangement of the infiltrate. Mucin proved to be a dermal-type mucin, composed of both hyaluronic acid and sulfated glycosaminoglycans. No differences were found in the composition of the follicular mucin in the PFM compared with LAFM. Conclusions: Although no single, indisputable feature can reliably differentiate PFM from LAFM and a considerable overlapping among the two groups exists, the use of multiple clinical, histological and immunopathological criteria associated with gene rearrangement analysis can be useful in evaluation of those patients.

Follicular mucinosis: a critical reappraisal of clinicopathologic features and association with mycosis fungoides and Sézary syndrome.Arch Dermatol. 2002 Feb;138(2):182-9.
CONTEXT: Beginning in 1957, patients have been described with localized alopecia characterized histopathologically by mucin deposition within hair follicles (follicular mucinosis [FM]). At least 2 distinct diagnostic entities have been proposed: one occurring in children and young adults without association with other diseases ("idiopathic" FM), the other occurring in elderly patients and associated with mycosis fungoides or Sézary syndrome ("lymphoma-associated" FM).
OBJECTIVE: To determine whether idiopathic and lymphoma-associated FM are distinct or related entities.
DESIGN: Case series.
SETTING: Department of Dermatology, University of Graz, Graz, Austria.
PATIENTS: Forty-four patients with FM were divided into 2 groups. Group 1 comprised 16 patients (mean age, 37.5 years) with no associated mycosis fungoides or Sézary syndrome; group 2 was made up of the other 28 (mean age, 52.2 years), who had clinicopathologic evidence of cutaneous T-cell lymphoma.
RESULTS: Mean age was lower in patients with idiopathic FM, but a considerable overlapping among the 2 groups was present. Location on the head and neck region was common in both groups, but most patients with lymphoma-associated FM had lesions also on other body sites. In fact, solitary lesions at presentation were common in patients with idiopathic FM (11 [68.8%] of 16 patients), but uncommon in those with lymphoma-associated FM (2 [7.1%] of 28 patients). Histopathologic findings did not allow clear-cut differentiation of the 2 groups. Finally, a monoclonal rearrangement of the T-cell receptor gamma gene was demonstrated by polymerase chain reaction analysis in about 50% of tested cases from each group.
CONCLUSIONS: Criteria previously reported to differentiate idiopathic from lymphoma-associated FM proved ineffective. In analogy to localized pagetoid reticulosis (Woringer-Kolopp disease), small-plaque parapsoriasis, and so-called solitary mycosis fungoides, idiopathic FM may represent a form of localized cutaneous T-cell lymphoma.


Follicular mucinosis associated with mycosis fungoides. Dermatol Online J. 2004 Nov 30;10(3):22.
A 62-year-old man with a 13-year history of mycosis fungoides presented with a 2-month history of alopecia of the scalp. The mycosis fungoides had remained untreated for the previous 3.5 years. A biopsy specimen from the scalp showed follicular mucinosis in association with mycosis fungoides.

Mycosis fungoides with follicular mucinosis displaying aggressive tumor-stage transformation : successful treatment using radiation therapy plus oral bexarotene combination therapy. Am J Clin Dermatol. 2003;4(6):429-33.
Follicular mucinosis is a tissue reaction pattern characterized by mucin deposition with follicular sebaceous units and is found as an idiopathic, primary, benign process (alopecia mucinosa), or as a secondary process due to inflammatory and neoplastic disorders (mycosis fungoides). When associated with follicular mucinosis, mycosis fungoides commonly pursues an aggressive course, often undergoing large-cell transformation, which is associated with resistance to therapy and poor prognosis. We present a case of mycosis fungoides with follicular mucinosis that was treated with incomplete courses of interferon, isotretinoin, and polychemotherapy with subsequent rapid progression to tumor-stage mycosis fungoides with large cell transformation and nodal and bone marrow involvement. In this setting, the patient was treated with local radiation therapy, total-skin electron beam therapy, and therapy and maintenance with the oral retinoid-X-receptor retinoid bexarotene, and achieved a durable complete remission.

Rapidly progressing mycosis fungoides presenting as follicular mucinosis. J Am Acad Dermatol. 2000 Oct;43(4):635-40.
Follicular mucinosis can occur as a primary idiopathic disorder or can arise in association with benign or malignant disease, most notably mycosis fungoides. We describe a patient with an aggressive folliculotropic variant of mycosis fungoides that initially presented as follicular mucinosis with alopecia. One month after the diagnosis of follicular mucinosis, a diagnosis of mycosis fungoides was made, and 3 months later inguinal lymph node involvement with mycosis fungoides developed. A skin biopsy specimen demonstrated prominent follicular mucinosis with folliculotropism of atypical cells and intrafollicular Pautrier's microabscesses. As demonstrated in this case, follicular mucinosis can be a presenting sign of rapidly progressive mycosis fungoides. In our review of follicular mucinosis and its association with mycosis fungoides, we found that the folliculotropic variant of mycosis fungoides appears more commonly to have an aggressive course than classic mycosis fungoides.

Dermatopathology Case 97

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Case 97

A 56 year old woman with violaceous follicular nodules and indurated plaques on the face and neck.

Tuesday, February 15, 2011

Answer of Dermatopathology Case 96

Immunohistochemistry: CD30 positive cells
[ CD3 & CD4 are faintly positive ; ALK and EMA -Negative]

Primary Cutaneous Anaplastic Large Cell Lymphoma

Abstracts:

Primary cutaneous anaplastic large-cell lymphoma.Dermatol Online J. 2010 15;16(11):2.

Primary cutaneous anaplastic large-cell lymphoma (ALCL) is a form of cutaneous T-cell lymphoma that is characterized by solitary or localized nodules or plaques. Histopathologic features include a diffuse, non-epidermotropic infiltrate with cohesive sheets of large anaplastic CD30+ tumor cells. This entity must be distinguished from systemic ALCL with cutaneous involvement and lymphomatoid papulosis. Treatment modalities include clinical monitoring, radiation therapy, and surgical excision, with systemic chemotherapy reserved for disseminated or extracutaneous disease.

CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood.2000 Dec 1;96(12):3681-95.

Anaplastic large cell lymphoma (ALCL) represents a generally recognized group of large cell lymphomas. Defining features consist of a proliferation of predominantly large lymphoid cells with strong expression of the cytokine receptor CD30 and a characteristic growth pattern. With the use of molecular and clinical criteria, 3 entities of ALCL have been identified: primary systemic anaplastic lymphoma kinase (ALK)(+) ALCL, primary systemic ALK(-) ALCL, and primary cutaneous ALCL. ALK expression is caused by chromosomal translocations, most commonly t(2;5). ALK(+) ALCL predominantly affects young male patients and, if treated with chemotherapy, has a favorable prognosis. It shows a broad morphologic spectrum, with the "common type," the small cell variant, and the lymphohistiocytic variant being most commonly observed. The knowledge of the existence of these variants is essential in establishing a correct diagnosis. ALK(-) ALCL occurs in older patients, affecting both genders equally and having an unfavorable prognosis. The morphology and the immunophenotype of primary cutaneous ALCL show an overlap with that of lymphomatoid papulosis. Both diseases have an excellent prognosis, and secondary systemic dissemination is only rarely observed. The described ALCL entities usually derive from cytotoxic T cells. In contrast, large B-cell lymphomas with anaplastic morphology are believed to represent not a separate entity but a morphologic variant of diffuse large B-cell lymphoma. Malignant lymphomas with morphologic features of both Hodgkin disease and ALCL have formerly been classified as Hodgkin-like ALCL. Recent immunohistologic studies, however, suggest that ALCLs Hodgkin-like represent either cases of tumor cell-rich classic Hodgkin disease or (less commonly) ALK(+) ALCL or ALK(-) ALCL.

Primary cutaneous anaplastic CD30(+) large-cell lymphoma that completely regressed after incisional skin biopsy. Cutan Ocul Toxicol. 2010 Nov 18.

We describe a 48-year-old woman with three erythematous nodules localized on the left forearm, with 2 months evolution. Histological and immunohistochemical examination revealed a CD30(+) large-cell lymphoma. Systemic involvement was not detected. The tumor regressed spontaneously within a week, after the incisional skin biopsy. In control skin biopsy, there was not any histological feature of lymphoma. No reactivation or any symptom of systemic disease was observed during the 10-month follow-up period.

Cutaneous anaplastic large cell lymphoma: clinicopathologic, immunohistochemical and prognostic study of 44 cases. Zhonghua Bing Li Xue Za Zhi. 2010 Apr;39(4):230-4.

OBJECTIVE: To study the clinicopathologic features, immunophenotype and prognosis of primary cutaneous anaplastic large cell lymphoma (CALCL).
METHODS: Histopathologic evaluation and immunohistochemical study by Envision method were carried out in 44 archival cases of CALCL. The clinical information and follow-up data were analyzed.
RESULTS: The patients presented with skin nodules, masses or plaques, sometimes associated with ulceration. The commonest sites of involvement were the extremities. Follow-up data were available in 39 patients. The overall survival rate was 87.2% (34/39). Disease relapses were detected in 46.2% (18/39) of the patients. Statistical analysis indicated that patients older than 50 years of age or with no less than two involved anatomic sites were more likely to have disease relapses.

Primary cutaneous anaplastic large cell lymphoma: clinical presentation, therapy and prognosis study of 10 cases.Zhonghua Yi Xue Za Zhi. 2010 May 11;90(18):1247-50.

OBJECTIVE: To explore the clinical presentation, therapy and prognosis study of primary cutaneous anaplastic large cell lymphoma (PCALCL).
METHODS: We reviewed and analyzed ten cases of PCALCL receiving treatment at our hospital from January 1999 to January 2009.
RESULTS: There were 8 males and 2 females with a median age of 48 years old (range: 22 - 69). There were single subcutaneous nodule (n = 7) and multiple nodules (n = 3). And the lesions could be found on head and neck (n = 5), trunk (n = 3) and all over body (n = 2). The lesions appeared red, solid and stable subcutaneous nodules. Partial lesions had a spontaneous regression and new nodules appeared at the same or different sites. Two patients had lymphadenopathy and one had bone involvement with anaplastic lymphoma kinase (ALK) positive and high cell proliferation ratio index (ki-67 > 80%). Seven cases with single lesion received surgical excision plus radiotherapy, chemotherapy or radiochemotherapy, one case recurred, six cases survived without disease. Three cases with multiple lesions received systemic chemotherapy mainly in combination with radiotherapy or biotherapy, two cases recurred and one case survived without disease. The median follow-up was 44 months (range: 9 - 95), progression free survival 89% and overall survival 100%.
CONCLUSION: PCALCL is found more commonly in males. Visceral and lymph node involvement are rare. The patients with single lesion have a longer disease-free survival than those with multiple lesions after surgical excision in combination with chemotherapy or radiotherapy. Multiple lesions can not be cured.

Dermatopathology Case 96

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Case 96

A 55 year old male with an ulcerated nodule on the back of the left arm.

Diagnosis

Saturday, February 12, 2011

Answer of Dermatopathology Case 95


Papillary Eccrine Adenoma

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Abstract:

Papillary eccrine adenoma in association with cutaneous horn. Am J Clin Dermatol. 2007;8(3):179-82.
Papillary eccrine adenoma (PEA) is an uncommon sweat gland neoplasm that occurs more frequently on the distal extremities of Black women. Clinically, it appears as a small, isolated, firm, dome-shaped cutaneous nodule. We report two unusual cases of PEA that presented clinically as cutaneous horn. Histologically, both cases showed the typical dermal morphology of PEA with overlying epidermal changes suggestive of human papillomavirus (HPV). However, HPV immunoperoxidase staining and polymerase chain reaction for HPV were negative in both cases. Concurrent occurrence of PEA and HPV-like epidermal changes may be coincidental; however, their co-occurrence may also be related to the environment induced by this adnexal tumor. Whether PEA with verrucous epidermal changes has a different clinical behavior or increased risk for a malignant transformation is unknown, as both patients were lost to follow-up.

Mohs micrographic surgery of a papillary eccrine adenoma.Dermatol Surg. 2002 Dec;28(12):1168-72.
BACKGROUND: Papillary eccrine adenoma (PEA) is a rare benign sweat gland neoplasm first described by Rulon and Helwig in 1977. Although these lesions typically behave in a benign fashion, PEA's on the volar surfaces may demonstrate more aggressive biologic behavior. Additionally, aggressive digital papillary adenomas (ADPA) may histologically simulate PEAs and behave in a more malignant fashion.
OBJECTIVE: To present a case report of a patient with an incompletely excised PEA that was successfully extirpated using Mohs micrographic surgery (MMS).
METHODS: A 51-year-old black woman was evaluated for the treatment of an incompletely excised PEA located on the dorsum of her left hand at the base of the thumb. Mohs micrographic surgery was felt to be the ideal treatment choice because of incomplete prior resections, ill-defined clinical borders, the need for conservative surgical excision to preserve sensory and motor function of the left hand, and the previously reported more aggressive nature of this tumor when located on volar surfaces. The patient underwent a two-stage, six section micrographically controlled excision using the fresh tissue technique.
RESULTS: Complete resection of the PEA without significant damage to neurovascular structures.
CONCLUSION: This case demonstrates the increasingly important role MMS is playing in the surgical management of a wide variety of cutaneous tumors. To our knowledge, this is the first time MMS has been used in the resection of a PEA.

Dermatopathology Case 95

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Case 95

A 45 year old male with a firm nodule on the dorsum of his right hand.


Diagnosis

Thursday, February 10, 2011

Answer of Dermatopathology Case 94





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Abstract:

Verrucous squamous cell carcinoma complicating hypertrophic lichen planus : Three case reports and review of the literature. Hautarzt. 2011 Jan;62(1):40-45.

Lichen planus is a chronic mucocutaneous T-cell-mediated disease, whose cause is still unknown. The first case of lichen planus that transformed into squamous cell carcinoma was reported in 1903. We present three patients in whom squamous cell carcinomas were identified in chronic lichen planus. The world literature includes at least 91 cases, including our three cases. In an epidemiological study, no significant risk of transformation of cutaneous lichen planus into squamous cell carcinomas was found. In contrast, there is a significantly higher risk of malignant transformation in mucosal lichen planus, so that the WHO had graded mucosal lichen planus as a premalignant condition.

Extensive hypertrophic lichen planus in an HIV positive patient. Dermatol Online J. 2010 Jun 15;16(6):8.

Individuals who are infected with Human Immunodeficiency Virus (HIV) suffer from numerous dermatoses. These disorders are often more severe than those observed in non HIV-infected persons afflicted with the same diseases. Lichen planus (LP) is a chronic inflammatory papulosquamous skin disorder. Herein, the diagnosis and treatment of a 40-year-old HIV+ Kenyan man afflicted with hypertrophic lichen planus (HLP) is described. In this case, lesions of HLP were widely distributed across the trunk and extremities, having become of such thickness on the dorsal surfaces of the hands and fingers as to make normal use of hands impossible. A significant distinguishing feature of this patient is prior history of tuberculosis, which is a known trigger for lichenoid skin lesions.

Hypertrophic lichen planus-like reactions combined with infundibulocystic hyperplasia: pathway to neoplasia. Arch Dermatol. 2004 Oct;140(10):1262-7.

BACKGROUND: Retinoids have the capacity to accelerate the involution of multiple keratoacanthomas, including unusual variants such as keratoacanthoma marginatum centrifugum and keratoacanthoma en plaque that may persist and be associated with progressive growth and provide difficulties in diagnosis and management.
OBSERVATIONS: We describe 3 patients who had unusual infiltrated and keratotic plaques affecting the lower legs or nasolabial area that persisted or recurred that may be related to this group of unusual keratoacanthomas. The 3 patients had differing clinical lesions that did not resemble classic keratoacanthomas, but were linked by their biopsy findings of hypertrophic lichen planus-like reaction and pseudoepitheliomatous hyperplasia with a prominent infundibulocystic component that progressed to multiple keratoacanthomas or infundibulocystic squamous cell carcinoma. Polymerase chain reaction analysis of biopsy material from 2 patients failed to detect human papillomavirus. All 3 presentations provided a therapeutic dilemma, but responded rapidly to acitretin treatment at a dosage of 10 to 25 mg daily, which was continued for 15 to 24 months.
CONCLUSIONS: These cases illustrate an unusual reaction pattern that is hypertrophic lichen planus-like but, instead of evolving to classic lichen planus, progresses to infundibulocystic hyperplasia and the development of multiple keratoacanthomas or infundibulocystic squamous cell carcinomas. Retinoids represent a therapeutic option for this difficult clinical problem and may obviate repeated and extensive surgery.

Giant keratoacanthoma arising in hypertrophic lichen planus.Australas J Dermatol. 2003 Nov;44(4):267-9.

A 45-year-old man presented with a rapidly enlarging tumour in an area of long-standing hypertrophic lichen planus of the lower leg. Histological examination of the resected specimen showed it to be a giant keratoacanthoma measuring 37 x 57 mm. Neoplastic change is a rarely reported complication of chronic variants of cutaneous lichen planus. To date there have been only two reports of keratoacanthoma development in association with lichen planus.

Dermatopathology Case 94

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Case 94

A 20 year old male with multiple pruritic plaques on the extremities. The lesions have a verrucous appearance.



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Wednesday, February 9, 2011

Answer of Dermatopathology Case 93

Giemsa stain

Toluidine Blue stain



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Abstract:

Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001 Jul;25(7):603-25.

The term 'mastocytosis' denotes a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MC) in one or more organ systems. Over the last 20 years, there has been an evolution in accepted classification systems for this disease. In light of such developments and novel useful markers, it seems appropriate now to re-evaluate and update the classification of mastocytosis. Here, we propose criteria to delineate categories of mastocytosis together with an updated consensus classification system. In this proposal, the diagnosis cutaneous mastocytosis (CM) is based on typical clinical and histological skin lesions and absence of definitive signs (criteria) of systemic involvement. Most patients with CM are children and present with maculopapular cutaneous mastocytosis (=urticaria pigmentosa, UP). Other less frequent forms of CM are diffuse cutaneous mastocytosis (DCM) and mastocytoma of skin. Systemic mastocytosis (SM) is commonly seen in adults and defined by multifocal histological lesions in the bone marrow (affected almost invariably) or other extracutaneous organs (major criteria) together with cytological and biochemical signs (minor criteria) of systemic disease (SM-criteria). SM is further divided into the following categories: indolent systemic mastocytosis (ISM), SM with an associated clonal hematologic non-mast cell lineage disease (AHNMD), aggressive systemic mastocytosis (ASM), and mast cell leukemia (MCL). Patients with ISM usually have maculopapular skin lesions and a good prognosis. In the group with associated hematologic disease, the AHNMD should be classified according to FAB/WHO criteria. ASM is characterized by impaired organ-function due to infiltration of the bone marrow, liver, spleen, GI-tract, or skeletal system, by pathologic MC. MCL is a 'high-grade' leukemic disease defined by increased numbers of MC in bone marrow smears (>or=20%) and peripheral blood, absence of skin lesions, multiorgan failure, and a short survival. In typical cases, circulating MC amount to >or=10% of leukocytes (classical form of MCL). Mast cell sarcoma is a unifocal tumor that consists of atypical MC and shows a destructive growth without (primary) systemic involvement. This high-grade malignant MC disease has to be distinguished from a localized benign mastocytoma in either extracutaneous organs (=extracutaneous mastocytoma) or skin. Depending on the clinical course of mastocytosis and development of an AHNMD, patients can shift from one category of MC disease into another. In all categories, mediator-related symptoms may occur and may represent a serious clinical problem. All categories of mastocytosis should be distinctively separated from reactive MC hyperplasia, MC activation syndromes, and a more or less pronounced increase in MC in myelogenous malignancies other than mastocytosis. Criteria proposed in this article should be helpful in this regard.

Evolution of urticaria pigmentosa into indolent systemic mastocytosis: abnormal immunophenotype of mast cells without evidence of c-kit mutation ASP-816-VAL. Leuk Lymphoma. 2003 Feb;44(2):313-9.

Mastocytosis comprises a heterogeneous group of hematological disorders which are morphologically defined by proliferation and accumulation of tissue mast cells in one or more organs. Clinical manifestations of mastocytosis range from disseminated maculopapular skin lesions (= urticaria pigmentosa [UP]) that may spontaneously regress to highly aggressive neoplasms like mast cell leukemia or mast cell sarcoma. Recently, it could be shown that systemic mastocytosis (SM) is a clonal disorder often exhibiting mutations of c-kit, a protooncogene encoding the tyrosine kinase receptor for stem cell factor (SCF). Mutations of c-kit are considered to play a key role in the pathogenesis of mastocytosis. Therefore, we investigated the unique case of a 36 year-old male patient with indolent systemic mastocytosis (ISM) evolving from UP (cutaneous mastocytosis) by means of histology, immunophenotyping and molecular biology. At the time of initial diagnosis the bone marrow showed only a mild diffuse increase in mast cells but compact infiltrates were missing. The serum tryptase levels were normal. Five years later, however, the bone marrow histology displayed patchycompact mast cell infiltrates, which now allowed to establish the diagnosis of an ISM. The serum tryptase levels at this time were markedly elevated. At both time points, mast cells were analyzed by immunohistochemistry using anti-tryptase antibody AA1, by flow cytometry using antibodies against CD2 and CD25, and nested polymerase chain reaction (PCR) on laser-microdissected, single pooled mast cells. Immunohistochemistry revealed strong tryptase-positivity of mast cells in both cutaneous and bone marrow infiltrates. Flow cytometry yielded an aberrant expression of CD2 and CD25 on bone marrow mast cells. However, repeated thorough PCR analysis failed to unveil c-kit mutation in atypical mast cells of skin and bone marrow samples of both dates. These findings clearly show that ISM can evolve from UP. Moreover, our study provides further evidence that the c-kit mutation Asp-816-Val is not invariably present in ISM.

Mastocytosis: state of the art. Pathobiology. 2007;74(2):121-32.

Mastocytosis is a neoplastic disease involving mast cells (MC) and their CD34+ progenitors. Symptoms in mastocytosis are caused by biological mediators released from MC and/or the infiltration of neoplastic MC in various organs, the skin and the bone marrow being predominantly involved. A WHO consensus classification for mastocytosis exists, which is widely accepted and includes three major categories: (1) Cutaneous mastocytosis (CM), a benign disease in which MC infiltration is confined to the skin, is preferentially seen in young children and exhibits a marked tendency to regress spontaneously. (2) Systemic mastocytosis (SM) which is commonly diagnosed in adults and includes four major subtypes: (i) indolent SM (ISM, the most common form involving mainly skin and bone marrow); (ii) a unique subcategory termed SM with an associated non-mast cell clonal hematological disease (SM-AHNMD); (iii) aggressive SM usually presenting without skin lesions, and (iv) MC leukemia, probably representing the rarest variant of human leukemias. (3) The extremely rare localized extracutaneous MC neoplasms, either presenting as malignancy (MC sarcoma) or as benign tumor termed extracutaneous mastocytoma. Diagnostic criteria for mastocytosis are available and are widely accepted. SM criteria include one major criterion (multifocal compact tissue infiltration by MC) and four minor criteria: (1) prominent spindling of MC; (2) atypical immunophenotype of MC with coexpression of CD2 and/or CD25 (antigens which have not been found to be expressed on normal/reactive MC); (3) activating (somatic) point mutations of the c-kit proto-oncogene usually involving exon 17, with the imatinib-resistant type D816V being most frequent, and (4) persistently elevated serum tryptase level (>20 ng/ml). To establish the diagnosis of SM, at least one major and one minor criterion, or at least three minor criteria, have to be fulfilled. The natural clinical course of mastocytosis is variable. Most patients, in particular those with CM and ISM, remain in an indolent stage over many years or even decades, while others, in particular those with aggressive SM, SM-AHNMD, or mast cell leukemia, show a progressive course, usually with a fatal outcome.

Dermatopathology Case 93

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Case 93

A 2 year old child with multiple reddish brown macules on the trunk.





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Sunday, February 6, 2011

Answer of Dermatopathology Case 92


Subcorneal Pustular Dermatosis (Sneddon-Wilkinson disease)

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Abstract:

Subcorneal pustular dermatosis: 50 years on.Clin Exp Dermatol. 2008 May;33(3):229-33. Epub 2008 Mar 18.

We review the key developments in our understanding of subcorneal pustular dermatosis (SCPD, also known as Sneddon-Wilkinson disease) over the past 50 years. SCPD is a rare, chronic, sterile pustular eruption that was first described by Sneddon and Wilkinson in 1956. The primary lesions are pea-sized pustules classically described as half-pustular, half-clear flaccid fluid blisters. Histologically the salient feature is a subcorneal accumulation of neutrophils, suggesting the presence of chemoattractants such as tumour necrosis factor (TNF)alpha in the uppermost epidermis. However, to date its exact pathophysiology is unknown. Cases in association with pyoderma gangrenosum, benign monoclonal IgA gammopathy and multiple myeloma are well documented. There are anecdotal reports of SCPD associated with other internal malignancies such as chronic lymphocytic leukaemia, thymoma, apudoma and epidermoid carcinoma of the lung. The treatment of choice is dapsone. Therapeutic alternatives include retinoids, phototreatment with psoralen ultraviolet (UV) A, broadband or narrow band UVB and corticosteroids. Anecdotal uses of tacalcitol, ketoconazole, azithromycin, tetracycline, minocycline, vitamin E, ciclosporin, colchicine, mizoribine, mebhydrolin, infliximab and adalimumab with mycophenolate mofetil have all been reported.

A case of subcorneal pustular dermatosis in association with monoclonal IgA gammopathy successfully treated with acitretin. J Dermatolog Treat. 2010 Mar;21(2):114-6.

Subcorneal pustular dermatosis (SPD), or Sneddon-Wilkinson disease, is a rare, chronic, recurrent, pustular eruption. Association with several diseases is well known, mainly IgA and IgG gammopathies or myelomas. Although dapsone is often considered to be the first-line treatment, some patients fail to respond or cannot tolerate the side effects. For cases that do not respond well to this treatment, acitretin, an excellent second-line treatment, may be used. Herein, a 55-year-old woman with SPD associated with monoclonal IgA gammopathy refractory to dapsone is presented, who was successfully treated with acitretin in a short period.

Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) with absence of desmoglein 1 and 3 antibodies: case report and literature review. Am J Clin Dermatol. 2008;9(1):51-5.

Subcorneal pustular dermatosis (SPD) [Sneddon-Wilkinson disease] is a benign and uncommon disorder characterized by a chronic, relapsing vesiculopustular eruption of unknown etiology. We present a case of SPD in a young Black woman in whom ELISA was performed to test for desmoglein 1 and 3 antigens (the first reported case of evaluation for these antigens in a patient with SPD). The test revealed the absence of both antibodies. The patient was successfully treated with topical corticosteroids and narrow-band UVB phototherapy. In this report, we review both the pathophysiology of SPD, which has yet to be clarified, and its treatment. Data obtained from our case report add further support to the hypothesis that a non-antibody-mediated mechanism is operative in SPD. The treatment of choice for SPD is dapsone. However, the combination of corticosteroids and UVB phototherapy should be considered a valid therapeutic option in patients who are not appropriate candidates for dapsone therapy.

[Sneddon-Wilkinson disease. Four cases report].Rev Med Interne. 2004 Feb;25(2):154-9.

INTRODUCTION: We report four cases of subcorneal pustular dermatosis or Sneddon-Wilkinson disease. Clinical and histological lesions and immunofluorescence data were presented. This disease is classified among neutrophilic dermatitis.
PATIENTS AND METHODS: All of four patients presented with clinical and histological lesions compatible with the diagnosis of Sneddon-Wilkinson disease. Indeed, direct and indirect immuno-testing were negative. We noted an association with a benign IgA monoclonal gammapathy in one case and with a seronegative polyarthritis in one other case. Three patients correctly responded to dapsone. One of them after transient improvement was resistant to dapsone and then dramatically responded to etretinate.
CONCLUSION: Subcorneal pustular dermatosis is a chronic disease, rarely described in literature. It's a pustular eruption, involving the trunck, axillae and inguinal holds. It's often associated with monoclonal gammapathy, particulary IgA. Its nosological situation is still contested, especially with IgA pemphigus sharing with it the association with IgA monoclonal gammapathy and the same efficacy of dapsone. We discuss relationships between both diseases.

Subcorneal pustular dermatosis type of IgA pemphigus: demonstration of autoantibodies to desmocollin-1 and clinical review.Br J Dermatol.2000;143(1):144-8.

We describe a 40-year-old Japanese man with a 3-year history of vesiculopustular lesions resembling subcorneal pustular dermatosis. Histopathology showed subcorneal pustules containing a few acantholytic cells, and direct immunofluorescence disclosed IgA deposition in the intercellular space of the upper epidermis. Circulating IgA autoantibodies of very low titre were also demonstrated by indirect immunofluorescence. A novel cDNA transfection technique clearly detected IgA autoantibodies reactive with human desmocollin-1. Combined therapy with dapsone and etretinate improved the skin lesions. We review the clinical features of 49 patients in the literature who presented with vesiculopustular lesions and intraepidermal IgA deposition.

Subcorneal pustular dermatosis treated with PUVA therapy. A case report and review of the literature. Dermatology.1999;198(2):203-5.

BACKGROUND: Subcorneal pustular dermatosis (SPD) is a chronic recurrent pustular dermatosis of unknown etiology. Many treatments have been proposed, none of which has been uniformly successful.
OBJECTIVE: Our purpose is to report a patient with SPD successfully treated by PUVA and to review the literature concerning phototherapy treatment of SPD.
METHODS: A patient suffering from SPD resistant to diaminodiphenylsulphone (dapsone) responded well to a combination therapy consisting of dapsone and PUVA. He received 50 mg/day and 3 PUVA sessions a week. Photographs were taken at baseline and after 15 sessions.
RESULTS: The lesions were virtually cleared after 15 sessions. The patient remained free of lesions with a maintenance therapy of dapsone (50 mg/ day) and 1 PUVA session a week.
CONCLUSION: The therapeutic value of phototherapy for the treatment of SPD still has to be confirmed and could be a valuable alternative for treatment-resistant patients.

Dermatopathology Case 92

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Case 92

A 52 year old woman, with pustules about 4 mm in diameter, on the neck.

Friday, February 4, 2011

Answer of Dermatopathology Case 91



Proliferating Trichilemmal Cyst (Pilar Tumour)

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Abstract:

Proliferating trichilemmal tumors: a review of the literature. Dermatol Surg. 2007 Sep;33(9):1102-8.

BACKGROUND: Proliferating trichilemmal tumors (PTTs) are uncommon lesions whose histologic hallmark is the presence of trichilemmal keratinization. PTT is thought to originate from the trichilemmal cyst (TC) and have the potential for malignant transformation, at which point it is termed a malignant proliferating trichilemmal tumor (MPTT). These lesions may cause considerable morbidity and even mortality, and recurrence after simple local excision is common.
OBJECTIVE: The objective was to review the clinical presentation, histopathologic characteristics, malignant potential, and treatment options for PTT.
METHODS: The English literature was reviewed regarding PTT, TC, and MPTT.
RESULTS: PTT generally presents as a subepidermal tumor on the scalp in women over the age of 60. Histologic findings may be used to differentiate PTT from TC and MPTT. Complete surgical excision is recommended; additional radiotherapy and/or chemotherapy may be used for lesions with increased invasive potential.
CONCLUSION: Adequate treatment of PTT requires skilled histopathologic examination for proper diagnosis; histologic appearance may not correlate with clinical behavior. After surgical excision, long-term clinical follow-up for evidence of metastatic disease is judicious.

Proliferating trichilemmal tumors: clinicopathologic evaluation is a guide to biologic behavior.J Cutan Pathol. 2003 Sep;30(8):492-8.

BACKGROUND: Trichilemmal (pilar) cysts are common skin lesions that usually occur on the scalp of elderly women. They differentiate towards the follicular outer root sheath epithelium and show trichilemmal keratinization. Proliferating trichilemmal tumor (PTT) shows features of typical pilar cyst, but additionally shows extensive epithelial proliferation, variable cytologic atypia and mitotic activity. The malignant potential of PTT is controversial, as only a small number of histologically malignant PTTs and a smaller number of clinically malignant PTTs have been reported.
METHODS: We retrieved from our archives five PTTs that deviated from ordinary PTTs with regards to either cytology or architecture. We also reviewed all previous reports of histologically malignant PTTs, with the goal of delineating criteria for the diagnosis of malignant PTTs.
RESULTS: Five cases of PTT showing atypical cytoarchitectural features were retrieved from our archives and reviewed with respect to size, growth pattern, cellularity, cytologic atypia, and mitotic activity. The patients (four female, one male) ranged from 54 to 83 (mean 65) years. The tumors measured from 1 to 16 cm in diameter (mean 5 cm) and four out of five occurred on the scalp. All tumors showed at least focal areas of typical PTTs. Three cases were circumscribed but had areas of moderate to focally marked cytologic atypia. Two cases showed infiltrative growth, marked cytologic atypia and mitotic activity. Clinical follow-up was available for four of five cases and ranged from 6 to 84 (median 48) months. Follow-up showed two cases with local recurrence and one case with distant metastasis. This last patient died of disease; all other patients are disease-free.
CONCLUSIONS: Review of our cases and the published literature suggests that the diagnosis of malignant PTT be given to PTT showing a combination of non-scalp location, recent rapid growth, size greater than 5 cm, infiltrative growth, and significant cytologic atypia with mitotic activity. At the present time the stratification of malignant PTT into low- and high-grade categories is not possible.

Proliferating trichilemmal cyst with focal invasion: report of a case and a review of the literature. Am J Dermatopathol. 2000 Apr;22(2):183-7.

Proliferating trichilemmal cyst (PTC) is a rare but morphologically distinctive tumor that usually occurs in the scalp of elderly women. Furthermore, only 30 well-documented examples of so-called malignant PTC have been reported. Alternatively, some authors have recently proposed that PTC is squamous cell carcinoma. We describe a case of PTC with focal invasion that was indistinguishable from squamous cell carcinoma in areas, and we review the literature. This debate should be considered in PTCs to provide adequate treatment (wide local excision) and follow-up (long term), particularly in large and long-standing lesions.

Dermatopathology Case 91

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Case 91

A nodule on the scalp of a 62 year old male.

Diagnosis

Thursday, February 3, 2011

Answer of Dermatopathology Case 90


Lichen Simplex Chronicus

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Abstract:

Lichen simplex chronicus of the anal region and its differential diagnoses. A case series.Hautarzt.2009 Nov;60(11):907-12.

Lichen simplex chronicus (LSC) of the anal region is characterized by massive pruritus, constant itching and a chronic course. Histology is notable for a pseudoepitheliomatous hyperplasia. Correct diagnosis as well as therapy of anal LSC sometimes is difficult. Differential diagnostic considerations include verrucous lichen planus and squamous cell carcinoma. We present three cases and then summarize pathogenesis, diagnostics, differential diagnoses and therapeutic options for lichen simplex chronicus of the anal region.

Clinical and histopathological findings of 'psoriatic neurodermatitis' and of typical lichen simplex chronicus. J Eur Acad Dermatol Venereol.2007 Jul;21(6):811-7.

BACKGROUND: We have seen several patients with itchy lichenified plaques located bilaterally on the elbows and/or knees and have named this condition 'psoriatic neurodermatitis' (PN).
OBJECTIVE: The purpose of this study was to compare clinical and histopathological characteristics of these patients to those of patients with typical lichen simplex chronicus (LSC).
METHODS: Nineteen patients with PN and 34 patients with typical LSC were included. Besides clinical dermatological evaluation, the prick test was carried out on 49 patients; the Phadiatop test on 40 patients; the patch test with European standard series on 47 patients; histopathological evaluation on 39 patients; and clinical psychiatric examination on 38 patients.
RESULTS: Almost exclusively, PN was seen in females and was located on the extremities. It caused more plaques than typical LSC did. In PN, the plaques were smaller, sharper, more keratotic and less excoriated, and had fewer lichenoid papules around them. Itching was usually more severe in the evening, while resting and in a hot environment in typical LSC, but not in PN. In plaques of PN, microabscesses in the horny layer, hypogranulosis, regular acanthosis and thinning of the suprapapillary plates were more frequent, and hyperpigmentation in the basal layer was less. In patients with PN, depressive disorder was found more frequently; and generalized anxiety disorder or psychosomatic characteristics, less. There were no significant differences in the results of prick, Phadiatop and patch tests between patients with PN and those with typical LSC.
CONCLUSION: In our opinion, it is most likely that the so-called PN is itchy psoriasis superimposed by LSC.

Unusual case presentation of lichen simplex chronicus, Hodgkin's lymphoma, and nonpuerperal hyperprolactinemia-galactorrhea.Endocr Pract. 2001 Sep-Oct;7(5):388-91.

OBJECTIVE: To report the association of nonpuerperal galactorrhea and severe pruritus with clinical stage IIB Hodgkin's lymphoma.
METHODS: We present a detailed history, findings on physical examination, laboratory data, and results of diagnostic imaging in a 25-year-old woman. A review of the related literature and speculations about possible etiologic factors for this association are provided.
RESULTS: Dermatologic evaluation of the patient revealed lichen simplex chronicus with multiple excoriations on the anterior chest area and lower extremities. High serum prolactin concentrations and easily expressible galactorrhea were present. Magnetic resonance imaging of the sella with 1-mm cuts, however, revealed a normal pituitary gland. Computed tomography showed multiple enlarged mediastinal lymph nodes, and a left supraclavicular lymph node biopsy revealed the presence of Reed-Sternberg cells and lymphocyte alterations consistent with the diagnosis of Hodgkin's lymphoma. After one cycle of chemotherapy for management of the lymphoma, parallel reductions in serum prolactin concentrations and galactorrhea were noted.
CONCLUSION: Possible causes for this syndrome include afferent mammary nerve stimulation resulting from scratching of pruritic skin and cytokine-induced hypersecretion of prolactin attributable to the lymphoma. Although uncommon, this syndrome may serve as an important harbinger of developing Hodgkin's lymphoma, and its disappearance may signify a therapeutic response.

Dermatopathology Case 90

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Case 90

A 36 year old female with scaly, thickened plaque on the extensor surface of left forearm. There is intermittent severe pruritis. Scratching of the area provides temporary relief.


Answer of Dermatopathology Case 89


Digital Mucous Cyst

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Abstracts:

Digital mucous cysts. J Cutan Med Surg. 2010 Sep-Oct;14(5):199-206
BACKGROUND: Digital mucous cyst (DMC) is a common benign condition, but consensus has not been reached regarding its pathogenesis and treatment.
OBJECTIVE: This review provides a concise overview of DMCs.
METHODS: The review presents the literature pertaining to the etiology, pathogenesis, classification, clinical features, epidemiology, differential diagnoses, diagnosis, and management of DMCs.
RESULTS: DMCs have a predilection for middle-aged patients, a good prognosis, and a high recurrence rate. DMCs may occur in one of three locations on the distal digit. They arise owing to a metaplastic or degenerative process. Preexisting osteoarthritis is common and may be an etiologic factor in patients with DMCs. A number of conservative and surgical treatments are available depending on the structures and locations involved.
CONCLUSION: Studies with greater sample size and longer follow-up would enrich current knowledge of the benefits, recurrences, and complications for each treatment modality.

A case of herpetiform appearance of digital mucous cysts. Ann Dermatol. 2010 May;22(2):194-5. Epub 2010 May 18.
A digital mucous cyst (DMC) is clinically characterized by a round to oval, translucent, smooth nodule localized to the dorsal aspect of the distal digits near the distal interphalangeal joint. It usually presents as a solitary lesion, and multiple lesions are uncommon. An 88-year-old man presented with herpetiform translucent papules on the right thumb. We first diagnosed the lesion as molluscum contagiosum or herpetic whitlow. Histopathology showed a cystic space containing mucinous material and numerous fibroblasts surrounded by mucinous stroma in the upper dermis. The lining of the cyst wall was not apparent and mucinous material was stained with Alcian blue, indicating a diagnosis of DMC.

MR imaging of digital mucoid cysts. Radiology. 1996 Aug;200(2):531-6.
PURPOSE: To assess the usefulness of magnetic resonance (MR) imaging in the diagnosis and clarification of the physiopathology of digital mucoid cysts.
MATERIALS AND METHODS: Twenty-three patients (14 women, nine men; aged 52-75 years) with mucoid cysts underwent MR imaging at 1.5 T with a local surface gradient coil. The pixel size was 117 microns in one direction. T2 relaxation times were measured. Contrast material was intravenously administered in 15 patients.
RESULTS: All mucoid cysts had high signal intensity and sharp borders on T2-weighted images. Intracystic septa were present in nine patients (39%). Most cysts were solitary (n = 13) and/or in the proximal nail fold (n = 16). Satellite cysts were present in five patients. Nineteen patients (83%) had cysts with pedicles that extended to the joint. Osteoarthritis of the distal interphalangeal joint was present in 16 patients (70%). Five patients (22%) had multiple flattened cysts that were usually independent of the joint. In seven patients (30%), MR images showed cysts beneath the nail plate.
CONCLUSION: Digital mucoid cysts may be polymorphic. MR imaging is helpful when cysts are in the nail bed.

Cutaneous mucinosis. Ann Dermatol Venereol. 1993;120(1):75-87.
The cutaneous mucinoses are a heterogeneous group of diseases in which mucin accumulates in the skin or within the hair follicle. We divide the cutaneous mucinoses into two groups: the distinctive cutaneous mucinoses in which the mucin deposit is a distinctive histopathologic feature that manifests as a clinically specific lesion, and the diseases associated with histopathologic mucin deposition as an additional finding. This article deals with the clinical and histopathologic features and the treatment of the distinctive cutaneous mucinoses and updates their classification. They may be divided, according to the microscopic location of mucin, into dermal and follicular mucinoses. The former group includes; lichen myxedematosus, acral persistent papular mucinosis, reticular erythematous mucinosis, scleredema, dysthyroidotic mucinoses (i.e. localized myxedema, generalized myxedema, papular mucinoses associated with thyroid diseases), papular and nodular mucinosis associated with lupus erythematosus, self-healing juvenile cutaneous mucinosis, cutaneous mucinosis of the infancy, cutaneous toxic mucinoses (papular mucinosis of the toxic oil syndrome and of eosinophiliamyalgia syndrome), neuropathia mucinosa cutanea, cutaneous focal mucinosis, mucous cyst (digital and of the oral mucosa), while the latter group includes Pinkus' follicular mucinosis and urticaria-like follicular mucinosis.

Dermatopathology Case 89

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Case 89

A 60 year old woman, with a oval dome-shaped fluctuant nodule. It is covered by thickened overlying skin. The lesion is located on the dorsolateral aspect of the left index finger, between the distal interphalangeal joint and proximal nail fold. The cystic nodule contains a viscous, gelatinous fluid.

Wednesday, February 2, 2011

Answer of Dermatopathology Case 88


Neurothekeoma (Nerve Sheath Myxoma)

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Abstract:

Nerve sheath myxoma with bidirectional schwannomatous and perineural differentiation. Cesk Patol.2010 Jul;46(3):73-6.
A case of nerve sheath myxoma occurring in occipital region in 70-yr-old woman is presented. The tumor showed typical lobular and myxoid morphology. Immunohistochemically, it showed unusual coexpression of Schwann cell markers S100 protein and GFAP with perineural cell markers EMA and claudin-1. CD34+ fibroblast-like cells were scarce, and nerve axons were not found in the tumor. Clinical pathology and histogenesis of the lesion are discussed.

Nerve sheath myxoma (neurothekeoma) of the gingiva, a case report and review of the literature. Head Neck Pathol. 2010 Sep;4(3):242-5. Epub 2010 May 26.
Nerve sheath myxoma (NSM) is a benign peripheral nerve sheath tumor that rarely occurs in the oral cavity. Among the 23 reported intraoral cases, no lesion has previously been reported on the gingiva. In this report, we describe the first gingival case of oral neurothekeoma with histopathologic and immunohistochemical characteristics. The patient, a 32 year old female presented with a slowly growing gingival mass diagnosed clinically as an epulis. The lesion was surgically excised. Histopathologically, the lesion presented as a submucosal multinodular mass composed of spindle and stellate-shaped cells with a myxoid background. Immunohistochemically, the tumor cells were sporadically positive for S-100 and NSE and negative for GFAP, EMA, SMA, CD68 and HMB45. The immunoprofile of this lesion confirmed a Schwann cell origin. The lesion was followed up for 10 months with no reports of recurrence.

Neurothekeoma palpebrae: A report of 3 cases. Am J Dermatopathol. 2010 Jun;32(4):374-9.
Neurothekeoma palpebrae is the diagnostic term used to describe nerve sheath myxoma or neurothekeoma of the eyelid. Although these tumors are not uncommonly found in the head and neck region, eyelid involvement is very uncommon. We present 2 cases of cellular neurothekeoma and 1 case of nerve sheath myxoma occurring in the eyelid. Patient 1 was a 13-year-old girl with a left upper eyelid lesion of 6-months duration. Microscopic examination disclosed a cellular neurothekeoma with mild myxoid change and osteoclast-like multinucleated cells. Tumor cells infiltrated the orbicularis oculi muscle. The tumor cells were immunopositive for NKI.C3, CD34, and focally for S-100 protein. Multinucleated cells were reactive to CD68. Mart-1, smooth muscle actin, CD31, keratin, desmin, myogenin, synaptophysin, and neurofilament protein (NFP) were negative. Patient 2 was a 4-year-old girl with a left upper eyelid lesion diagnosed clinically as a chalazion. The lesion was incised. Five months later, the patient returned with a firm 5.5-mm nodule at the site. Excision revealed cellular neurothekeoma invading the orbicularis oculi. Tumor cells were NKI.C3 immunopositive and S-100 protein negative, and the multinucleated cells were CD68 positive. Patient 3 was a 70-year-old woman with a 10-year history of a subcutaneous right lower eyelid nodule which had recently changed color. The excised specimen demonstrated a hypocellular, well-circumscribed myxoid tumor surrounded by a thin rim of fibrous connective tissue. Tumor cells contained moderate amounts of eosinophilic cytoplasm with irregular, hyperchromatic nuclei. Nucleoli and mitotic figures were not apparent. Tumor cells were NKI.C3 negative, and S100 protein and glial acidic fibrillary protein positive, consistent with a nerve sheath myxoma. Including our 3 cases, 10 cases of nerve sheath myxoma and neurothekeoma occurring in the eyelid have been reported the English language literature. Although uncommon, these lesions should be kept in the differential diagnosis of eyelid tumors that can masquerade as chalazia.

Neurothekeoma: an analysis of 178 tumors with detailed immunohistochemical data and long-term patient follow-up information. Am J Surg Pathol. 2007 Jul;31(7):1103-14.
This report describes the clinicopathologic findings in 176 patients who presented with 178 tumors currently referred to as neurothekeomas. Our study group included 64 males and 112 females, ranging from 20 months to 85 years old at the time of their first surgical procedure (median age: 17 y). Twenty-four percent of patients were or=30 years of age at initial diagnosis. The patients typically presented with a solitary, superficial, slow-growing, and relatively asymptomatic mass in the 0.3 to 2.0 cm size range. One patient had multiple tumors. More than 75% of the lesions involved the head (n=63), upper extremities (n=44), and shoulder girdle (n=27) regions. The tumors were evident a few weeks to 4 years (median duration: approximately 7 mo) before surgical resection was sought. Histologically, the lesions involved the dermis and/or subcutis, and they formed multinodular masses with varying amounts of myxoid matrix and peripheral fibrosis. On the basis of the amount of myxoid matrix, the tumors were subclassified as cellular (n=63), mixed (n=67), or myxoid (n=48). All cases had spindled and epithelioid mononuclear neoplastic cells with relatively abundant cytoplasm and indistinct cell borders. The majority of cases also had occasional multinucleated tumor cells. The lesional cells had a strong tendency for whorled growth, and oftentimes, focal fascicular growth was also present. Nuclear atypia was minimal in 62 cases, mild in 73 cases, at least focally moderate in 41 cases, and focally marked in 2 cases. Mitotic activity ranged from 0 to 124 mitotic figures/25 wide-field high power fields (WHPFs) (median mitotic count: 4 mitotic figures/25WHPFs). Twenty-five lesions had >10 mitotic figures/25WHPFs. A total of 16 cases (9%) had atypical mitotic figures. Osteoclastlike giant cells were detected in 39% of cases. Immunoreactivity was typically present for vimentin, NKI/C3, CD10, microphthalmia transcription factor, and PGP9.5, and focal reactivity was sometimes noted for smooth muscle actin and CD68. All tumors tested were negative for S100 protein, glial fibrillary acidic protein, and Melan A. The overwhelming majority of cases had involvement of the tissue margins. A complete follow-up record is available for 71 patients (40.3%) with follow-up intervals ranging from 3 years 2 months to 34 years 9 months (median: 17 y 9 mo). Limited or incomplete follow-up information is also available for an additional 14 patients with follow-up intervals ranging from weeks to approximately 10 years (median: 5 mo). Regrowth of tumor after biopsy or local excision was reported in 13 patients, one of whom had 2 recurrences. However, because of the nature of our consultation practice and a tendency for clinicians to specifically send us cases with a complex clinical course, this is believed an overestimation of the true recurrence rate. Neurothekeomas are morphologically and immunohistochemically distinct from true nerve sheath myxomas. An origin from fibroblastic cells with the ability to differentiate into myofibroblasts and a tendency to recruit histiocytic cells is postulated.

Dermatopathology Case 88

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Case 88

A 35 year old man with a nodule on the left index finger.

Answer of Dermatopathology Case 87


Angiokeratoma

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Abstract:

Angiokeratoma: a cutaneous marker of Fabry's disease. Clin Exp Dermatol. 2010 Jul;35(5):505-8. Epub 2009 Oct 19.
The initial symptoms of Fabry's disease (FD) may seem harmless and may delay its diagnosis. A survey and screening for FD were performed on men with biopsy-proven angiokeratoma and some of their relatives (n = 29). Three patients were identified. Dermatologists should be aware of this prominent early feature and investigate unexplained cutaneous vascular lesions to detect FD.

Solitary angiokeratoma of the tongue in adults. Rom J Morphol Embryol.2010;51(4):771-3.
Angiokeratomas are vascular malformations that usually appear as multiple or solitary cutaneous plaques. Several clinical variants have been described, with the same underlying histopathological lesion. Mucosal involvement, including the oral cavity, is occasionally found either as a component of the systemic variety, called angiokeratoma corporis diffusum, or associated with cutaneous lesions in more locations. Isolated oral involvement seems to be rather infrequent and only five cases have been described in adults in the world literature. We herein report another case of this rare entity affecting a 62-year-old woman in the dorsum at the tip of the tongue. This is the first report including an immunohistochemical study to discard a lymphatic origin of the tumor.

Angiokeratoma presenting as plantar verruca: a case study. J Am Podiatr Med Assoc.2010 Nov-Dec;100(6):502-4.
One of the more frequent pathologic conditions that podiatric physicians are confronted with is plantar verrucae. Plantar verrucae have been studied extensively in terms of morphological features and incidence in the population at large and in patients with human immunodeficiency virus infection. Solitary angiokeratomas can be morphologically similar to plantar verrucae, presenting as hyperkeratotic pedunculated lesions. We present a unique case study of a 40-year-old man with human immunodeficiency virus with a painful solitary angiokeratoma masquerading as plantar verrucae. The lesion demonstrated clinical signs consistent with those highlighted in the literature for verrucae, namely, showing as red and black lacunae, punctuated hyperkeratotic epidermis. We propose that solitary angiokeratomas should be an important part of a podiatric physician's differential diagnosis in the lower extremity owing to the similarity of morphological features with plantar verrucae.

Solitary angiokeratoma of the tonsillar pillar of the oral cavity. Rom J Morphol Embryol.2009;50(1):115-7.
Solitary angiokeratoma has rarely been described in oral mucosa, mainly in the tongue, where the main concern is either aesthetical or due to bleeding problems. We present a case of solitary angiokeratoma of the tonsillar pillar in a 68-year-old man. Histologically, the morphology was typical of angiokeratoma. It showed an immunohistochemical pattern in consonance with a blood vessel origin, with expression of CD31, CD34, and von Willebrand factor. The lesion did not express D2-40. No other malformation or metabolic disorder was found in the patient. The lesion was surgically removed and due to the disproportionate post-surgery bleeding, the patient was studied by the Hematology Service, and she was diagnosed as an inhibitor of Factor VIII carrier.

Angiokeratomas: an update.Dermatology.1996;193(4):275-82.
Angiokeratomas are vascular lesions which are defined histologically as one or more dilated blood vessel(s) lying directly subepidermal and showing an epidermal proliferative reaction. At the center of pathogenesis there is a capillary ectasia in the papillary dermis. The epidermal changes in all forms of angiokeratoma are secondary. The different entities causing vessel ectasia lead to the many clinical variants of angiokeratoma. Current classification distinguishes between widespread forms (angiokeratoma corporis diffusum), which is usually associated with an inborn error of metabolism, and localized forms, which include solitary angiokeratoma, Fordyce's angiokeratoma, angiokeratoma circumscriptum naeviforme and angiokeratoma of Mibelli.

Angiokeratoma of the vulva: diagnosis and review of the literature. Obstet Gynecol Surv.1989 May;44(5):339-46.
Angiokeratomas of the vulva are uncommon benign lesions. They are usually unilateral, multiple in number, and occur before the age of 50 years. Angiokeratomas are papular lesions measuring less than 1 cm in diameter and are purple in color. In most patients the lesions are asymptomatic; however, intermittent bleeding, pruritus, and pain have been reported. Histologically, hyperkeratosis, papillomatosis, acanthosis, and dilated vasculature in the papillary dermis are characteristic features. Degenerative changes in the perivascular elastic tissue is observed and may contribute to the pathogenesis of vulvar angiokeratomas. In asymptomatic patients, management need only include reassurance and follow-up observation; surgical excision, electrodesiccation, or argon laser for local removal of the lesions may be useful in symptomatic women. Clinically, infections, inflammatory lesions, vascular conditions, and epithelial tumors must be differentiated.

Dermatopathology Case 87

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Case 87

Skin biopsy- Images for spot diagnosis?

Diagnosis