The American Journal of dermatopathology

Publications in this journal

• Article: Paraneoplastic Scleroderma-Like Tissue Reactions in the Setting of an Underlying Plasma Cell Dyscrasia: A Report of Ten Cases.

  Cynthia M Magro, Hans Iwenofu, Gerard J Nuovo
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  ABSTRACT: INTRODUCTION:: Systemic plasma cell dyscrasias have diverse manifestations in the skin and include an inflammatory paraneoplastic process. We encountered cases of scleroderma and eosinophilic fasciitis in the setting of an underlying plasma cell dyscrasia. MATERIALS AND METHODS:: Ten cases of scleroderma-like tissue reactions in the setting of an underlying plasma cell dyscrasia were encountered. The biopsies were stained for Transforming growth factor (Transforming growth factor) beta, IgG4, kappa, and lambda. RESULTS:: Patients presented with a sclerodermoid reaction represented by eosinophilic fasciitis (5 cases), morphea (3 cases), and systemic scleroderma (2 cases). The mean age of presentation was 70 years with a striking female predominance (4:1). Acral accentuation was noted in 8 cases. In 6 of the cases, the cutaneous sclerosis antedated (4 cases) by weeks to 2 years or occurred concurrently (2 cases) with the initial diagnosis of the plasma cell. The biopsies showed changes typical of eosinophilic fasciitis and/or scleroderma. In 5 cases, light chain-restricted plasma cells were present on the biopsy. There was staining of the plasma cells for Transforming growth factor beta in 3 out of 5 cases tested. CONCLUSIONS:: In any older patient presenting with a sudden onset of eosinophilic fasciitis or scleroderma especially with acral accentuation, investigations should be conducted in regards to an underlying plasma cell dyscrasia.
  The American Journal of dermatopathology 05/2013;
• Article: Difficulty in Confirming the Diagnosis of Bullous Amyloidosis.

  Akihiko Asahina
  The American Journal of dermatopathology 05/2013;
• Article: Expression of Lumican in Hidroacanthoma Simplex and Clonal-Type Seborrheic Keratosis as a Potent Differential Diagnostic Marker.

  Ryoko Takayama, Shin-Ichi Ansai, Toshiyuki Ishiwata, Tetsushi Yamamoto, Yoko Matsuda, Zenya Naito, Seiji Kawana
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  ABSTRACT: : Lumican, a member of the small leucine-rich proteoglycan family, regulates the assembly and diameter of collagen fibers in the extracellular matrix of various tissues. The lumican expression correlates with pathological conditions and the growth and metastasis of various malignancies. In cutaneous neoplasms, the lumican expression is lower in advanced-stage malignant melanomas that invade the dermis than in early-stage melanomas. Furthermore, we have recently reported that the expression pattern of lumican is different from that of actinic keratosis and the Bowen disease. Lumican is positive in the poroid cells of intraepidermal sweat ducts; therefore, we examined the expression patterns of lumican in acanthotic-type seborrheic keratosis and Pinkus-type poroma followed by clonal-type seborrheic keratosis and hidroacanthoma simplex. The neoplastic cells of acanthotic-type seborrheic keratosis exhibited positive immunostaining in only 1 of 31 cases (3.23%), whereas the poroid cells of Pinkus-type poroma exhibited positive immunoreactivity in 26 of 28 patients (92.8%). In the hidroacanthoma simplex cases, lumican was expressed in poroid cells forming intraepidermal nests in 22 of 28 patients (78.6%), whereas the neoplastic cells in most cases of clonal-type seborrheic keratosis were negative for lumican. In some seborrheic keratosis cases that were positive for lumican in neoplastic cells, lumican was observed in squamoid cells but not in basaloid cells. Therefore, it is necessary to evaluate the immunoreactivity of lumican in seborrheic keratosis and in basaloid cells. These findings suggest that lumican is a potent differential diagnostic marker that distinguishes hidroacanthoma simplex from clonal-type seborrheic keratosis.
  The American Journal of dermatopathology 05/2013;
• Article: Lichen Aureus: An Unusual Histopathological Presentation: A Case Report and a Review of Literature.

  Phyu P Aung, Stacey J Burns, Jag Bhawan
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  ABSTRACT: : Lichen aureus (LA) presents an inflammatory infiltrate with a lichenoid pattern, which mainly localizes to the superficial dermis, and it is admixed with extravasated erythrocytes. We present the case of a 12-year-old male who had a 1.3-cm golden-brown-color patch on the right upper back for 2 weeks. Histopathologic examination revealed a lichenoid, superficial, and deep perivascular lymphocytic infiltrate with perineural and periappendageal involvement, extravasated erythrocytes, papillary dermal edema, and hemosiderophages. The perineural and periappendageal infiltrate is unusual for LA and suggestive of lichen striatus (LS). In addition, the presence of perineural inflammation is not a common feature for either LA or LS. However, given the clinical findings, taken together, these features were interpreted as being most consistent with LA. To the best of our knowledge, no previous case of LA has been reported with histological features of perineural inflammation and LS.
  The American Journal of dermatopathology 05/2013;
• Article: Dermatopathology of the Female Breast.

  Margot S Peters, Julia S Lehman, Nneka I Comfere
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  ABSTRACT: : To better define the spectrum of neoplastic and inflammatory diseases that affect female breast skin and the nipple-areola complex, we searched an institutional dermatopathology database and identified 500 specimens of female "breast" (from consecutive records accessioned January 2009-March 2011), 143 specimens of "areola," 124 specimens of "nipple" (records from the latter 2 groups were from patients evaluated June 1992-March 2011), and 500 control specimens of "abdomen" (accessioned January 2010-March 2011). Most specimens obtained from breast skin (76%) represented melanocytic or epithelial proliferations (eg, nevi, seborrheic keratoses, and cysts), as did those from the abdomen, whereas many from the nipple (41%) and areola (60%) were of inflammatory dermatoses. A striking finding was eosinophilic spongiosis (ES) in most areola specimens with spongiotic dermatitis (78%); in contrast, ES was identified in 50% and 31% of spongiotic dermatitis specimens from nipple and breast skin, respectively. ES was associated with a clinical diagnosis of dermatitis in all patients except one (who had pemphigus). Metastatic breast cancer was identified in 28 of 767 specimens (4%), including 6 of 124 (5%) from the nipple. Five of 124 specimens from the nipple (4%) and 1 of 143 from the areola (1%) showed Paget disease. All but one patient with Paget disease showed acantholytic features and none had tissue eosinophils. Abnormalities categorized as complications of radiotherapy, including mild fibrosis and vascular ectasias, morphea, and angiosarcoma, constituted a minority of cases. Our data and the literature indicate that few disorders specifically affect breast skin, but the nipple-areola complex should be approached with a different set of diagnostic considerations.
  The American Journal of dermatopathology 05/2013; 35(3):289-307.
• Article: Expression of p75 Neurotrophin Receptor in Desmoplastic Trichoepithelioma, Infiltrative Basal Cell Carcinoma, and Microcystic Adnexal Carcinoma.

  Jaroslaw Jedrych, Jennifer M McNiff
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  ABSTRACT: : The histological discrimination between desmoplastic trichoepithelioma, infiltrative basal cell carcinoma, and microcystic adnexal carcinoma encountered in small biopsies is challenging when only morphological criteria are applied. The objective of this study is to test the use of p75 neurotrophin receptor (p75NTR) as an adjunct aid in classification of these tumors. Immunohistochemistry for p75NTR antigen was performed on routinely processed biopsies of 37 desmoplastic trichoepitheliomas, 11 infiltrative basal cell carcinomas, and 9 microcystic adnexal carcinomas diagnosed by morphological criteria in conjunction with results of CK20 immunostains. Cases were analyzed for the extent and intensity of p75NTR expression. Diffuse immunoreactivity was defined as involving >90% of tumor cells. Of the 37 desmoplastic trichoepitheliomas, 35 (94%) displayed strong diffuse immunoreactivity of tumor cells, proving high sensitivity of the marker to detect this tumor. However, despite the fact that diffuse p75NTR expression reached statistical significance in differentiating desmoplastic trichoepithelioma from infiltrative basal cell carcinoma (Fisher exact test P < 0.0001) and microcystic adnexal carcinoma (P < 0.0016), specificity of the stain is unsatisfactory because strong diffuse expression of p75NTR by neoplastic cells was observed in 4 (36%) cases of infiltrative basal cell carcinomas and 4 (44%) cases of microcystic adnexal carcinoma. This study demonstrates a significant difference in p75NTR expression in selected sclerosing neoplasms of the skin. Nevertheless, the practical value of p75NTR as an adjunct marker in the differential diagnosis of these tumors seems to be limited because of significant overlap in amount of p75NTR immunoreactivity.
  The American Journal of dermatopathology 05/2013; 35(3):308-315.
• Article: Febrile Ulceronecrotic Mucha-Habermann Disease (Pityriasis Lichenoides et Varioliformis Acuta Fulminans) Associated With Parvovirus Infection.

  Arti Nanda, Faisal Alshalfan, Mohammad Al-Otaibi, Humoud Al-Sabah, Jihan M Rajy
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  ABSTRACT: : Febrile ulceronecrotic Mucha-Habermann disease is a rare fulminant variant of pityriasis lichenoides et varioliformis acuta, characterized by a rapidly progressive course with predominant ulceronecrotic lesions associated with fever and systemic manifestations. It carries a great morbidity and is potentially fatal. The exact pathogenesis is not clear, and it has been proposed to be the result of hypersensitivity reaction to an infection. We report a patient with febrile ulceronecrotic Mucha-Habermann disease in a 12-year-old boy in whom the condition was most likely precipitated by parvovirus infection, and he showed a favorable response to a combination of prednisolone with narrow band ultraviolet B (NB-UVB) phototherapy.
  The American Journal of dermatopathology 04/2013;
• Article: Primary Cutaneous Mantle Cell Lymphoma of the Leg With Blastoid Morphology and Aberrant Immunophenotype: A Diagnostic Challenge.

  Anna Maria Cesinaro, Stefania Bettelli, Livia Maccio, Marina Milani
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  ABSTRACT: : Mantle cell lymphoma rarely affects the skin and is usually a secondary involvement. The present case illustrates a primary cutaneous mantle cell lymphoma of the leg, with blastoid morphology and aberrant expression of CD10 and bcl-6, which was misinterpreted at the beginning as diffuse large B-cell lymphoma. A larger panel of immunohistochemical markers, including cyclin-D1, and molecular investigation showing the typical translocation (t11;14), pointed toward the correct diagnosis. Cutaneous diffuse B-cell lymphomas with unusual morphology should be interpreted cautiously, and the diagnosis made on the basis of an appropriate panel of antibodies and molecular studies.
  The American Journal of dermatopathology 04/2013;
• Article: PAX-8 Expression in Primary and Metastatic Merkel Cell Carcinoma: An Immunohistochemical Analysis.

  Ankur R Sangoi, David S Cassarino
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  ABSTRACT: : PAX-8, a nephric cell lineage transcription factor initially characterized in renal cell carcinomas, is also well recognized as a marker of Müllerian tract and thyroid tumors. From a previous tissue microarray study of nonrenal neoplasms including a variety of skin tumors, we identified PAX-8 staining in a small set of Merkel cell carcinomas, a finding not previously described. Herein, we explore PAX-8 immunoreactivity in 34 whole-section Merkel cell carcinomas (24 primary, 10 metastatic) using polyclonal PAX-8 (prediluted) and 2 varieties of monoclonal PAX-8 (prediluted clone MRQ-50 and 1:100 dilution clone BC12). Nuclear staining intensity and extent was semiquantitatively analyzed with a comparison of staining thresholds required for a "positive" result (≥2+ vs. 1+). Thirty-three of 34 (97%) cases showed positive Cell Marque polyclonal PAX-8 staining, whereas 31 of 34 (91%) cases showed positive Cell Marque monoclonal PAX-8 staining. There was no significant difference in staining between primary versus metastatic tumors. The Cell Marque polyclonal PAX-8 was superior to their monoclonal PAX-8, maintaining strong sensitivity using a ≥2+ versus 1+ staining cut point for positive results (79% vs. 18%, respectively), which may be important in cases with scant tissue or background staining. The Biocare monoclonal PAX-8 was negative in all cases. PAX-8 staining in Merkel cell carcinoma expands the spectrum of tumors showing immunoreactivity and may prove to be a useful addition to a diagnostic panel. Awareness of this immunoreactivity and recognition of the antibody source and clone are important to preclude diagnostic pitfalls with tumors in the differential diagnosis.
  The American Journal of dermatopathology 04/2013;
• Article: Acquisition of CD30 and CD15 Accompanied With Simultaneous Loss of All Pan-T-Cell Antigens in a Case of Histological Transformation of Mycosis Fungoides With Involvement of Regional Lymph Node: An Immunophenotypic Alteration Resembling Classical Hodgkin Lymphoma.

  Deepti M Reddi, Siby Sebastian, Endi Wang
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  ABSTRACT: : Acquired expression of CD30 is frequently noted in histological transformation of mycosis fungoides (MF), but simultaneous gain of CD15 accompanied with loss of pan-T-cell antigens are extremely rare. We report an unusual case of transformed MF with such an immunophenotypic alteration resembling classical Hodgkin lymphoma. The patient was an 81-year-old male with MF, who was initially treated with topical steroids and phototherapy. Despite the initial response, the patient developed a tumor-like skin lesion that was confirmed to be CD30-positive large T-cell lymphoma and was subsequently found to have a regional lymph node involvement by pleomorphic large cell lymphoma. Besides CD30, pleomorphic large cells were positive for CD15 but negative for all B cell- and T cell-specific antigens. Epstein-Barr virus was negative. Polymerase chain reaction-based assays demonstrated a clonal rearrangement of T-cell receptor gamma gene but detected no B-cell clone. The mechanism and clinical significance of this phenotypic conversion remains to be elucidated.
  The American Journal of dermatopathology 04/2013;
• Article: Perforating Folliculitis in a Patient Treated With Nilotinib: A Further Evidence of C-kit Involvement.

  Mar Llamas-Velasco, Juan Luis Steegmann, Raquel Carrascosa, Javier Fraga, Amaro García Diez, Luis Requena
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  ABSTRACT: : We present a case of perforating folliculitis in a patient treated with nilotinib, a kinase inhibitor. A 48-year-old man presented with a severely pruritic follicular rash for several months that started after reaching a complete molecular response of his myeloid chronic while treated with nilotinib. Clinical examination showed predominantly follicular pinpoint papules on trunk and proximal extremities and a biopsy showed a slightly dilated hair follicle with a focal disruption of the infundibular follicular epithelium. Other diseases related with perforating folliculitis were ruled out. The temporary relationship between the treatment and the appearance of the lesions suggests some pathogenic role of nilotinib. Relationship with nilotinib is also supported by previous similar cases related with sorafenib therapy. Both drugs inhibit c-kit and PDGF-R. PDGF-R has been previously involved in murine and human in vitro models of hair follicle cycle. So, our case supports in vivo the previous evidence of the importance of PDGF-R, a kinase, in the normal hair follicle development.
  The American Journal of dermatopathology 04/2013;
• Article: Scleroderma and IgG4-Related Disease.

  Deepti M Reddi, Diana M Cardona, James L Burchette, Puja K Puri
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  ABSTRACT: : IgG4-related disease is a syndrome which involves lymphoplasmacytic infiltrates and soft tissue sclerosis, elevated serum IgG4 titer, and increased IgG4-positive plasma cells in a variety of tissues. Scleroderma is also characterized by fibrosis and lymphoplasmacytic infiltrates. To our knowledge, the presence of IgG4-positive cells has not been well characterized in scleroderma. A retrospective review of scleroderma and related disorders (calcinosis, raynaud's syndrome, esophageal dysmotility, sclerodactyly, telangiectasia (CREST) syndrome, progressive systemic sclerosis, morphea) was performed. Thirty-four cases of scleroderma and related disorders were identified; IgG4-positive and IgG-positive plasma cells were counted in 10 HPF and an IgG4:IgG ratio determined. A cutoff ratio of 0.3 was used to define significant elevation. Three of the scleroderma cases had IgG4:IgG greater than 0. Only 1 case had a significant elevation. Of the 3 cases with elevated ratio, IgG4-positive cells ranged from 2 to 64 (median = 14), with an IgG4:IgG ranging from 0.06 to 0.34 (median = 0.22). Similar results were produced with the other sclerosing disorders. These results suggest that scleroderma is not part of the IgG4-related disease spectrum.
  The American Journal of dermatopathology 04/2013;
• Article: Herpes Folliculitis Masquerading as Cutaneous Lymphoma.

  Yoon-Soo C Bae-Harboe, Jag Bhawan, Marie-France Demierre, Lynne J Goldberg
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  ABSTRACT: : Herpes virus infections presenting as folliculitis are uncommon. We describe a 48-year-old white man with a distant history of a childhood gastric lymphoma and renal cell carcinoma presenting with an itchy eruption. He was concerned about recurrence. A punch biopsy revealed interface dermatitis with a dense atypical superficial and deep perivascular and periadnexal lymphohistiocytic infiltrate with occasional eosinophils extending to the subcutis, with destruction of vessel walls. It was composed of predominantly CD3-positive lymphocytes with scattered CD56-positive cells and CD20-positive cells, concerning for lymphoma. A T-cell gene rearrangement study was negative. Deeper sections uncovered multinucleated giant keratinocytes in the follicular epithelium of 1 hair follicle, consistent with herpes folliculitis. Cutaneous herpes infections can exhibit several variable clinical and histopathological features. Knowledge of alternative presentations of herpes infections, histological clues to the presence of herpes infections, and careful clinicopathological correlation are necessary to differentiate herpes infections from cutaneous lymphomas and other inflammatory dermatoses.
  The American Journal of dermatopathology 04/2013;
• Article: Circumscribed Palmar or Plantar Hypokeratosis: First Report on a Nonacral Site With Unique Histologic Features.

  Tatyana Groysman, Jeremy Rothfleisch, Marisa F Baldassano
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  ABSTRACT: : Circumscribed palmar or plantar hypokeratosis was first described by Pérez et al in 2002 as a unique entity of the skin in which they reported 10 patients who presented with well-circumscribed areas of erythematous depressed or eroded skin mostly over the thenar or hypothenar eminences of the palms and less commonly on the soles. Histologically, the lesions demonstrated an abrupt drop-off in the cornified layer resulting in a broad area of hypokeratosis. Pérez et al hypothesized that these lesions were a distinctive epidermal malformation. There have been several reports since, some of which implicate trauma as an etiologic agent; however, the exact etiology remains unclear. The authors present the first case of circumscribed palmar or plantar hypokeratosis on a nonacral site (chest of a 63-year-old man) with novel histological features, including granular parakeratosis and evidence of trauma (subepidermal fibrin and ulcerations).
  The American Journal of dermatopathology 04/2013;
• Article: Multiple Scattered Violaceous Papules and Nodules.

  Lyndsay R Shipp, Darya P Shlapak, Michael Toscano, Loretta S Davis
  The American Journal of dermatopathology 04/2013;
• Article: Superficial Soft Tissue Biphasic Synovial Sarcoma With Apocrine Differentiation in the Glandular Component: A Report of Two Cases.

  Ksenya V Shelekhova, Eduardo Calonje, Petr Grossmann, Denisa Kacerovska, Karel Koudela, Hynek Mirka, Michal Michal, Dmitry V Kazakov
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  ABSTRACT: : The authors present 2 cases of a subcutaneous biphasic synovial sarcoma with marked apocrine differentiation that potentially may be confused with cutaneous epithelial neoplasms, including malignant apocrine mixed tumor or metaplastic carcinoma with an apocrine glandular component. Microscopically, both neoplasms had a biphasic architecture with the epithelial and spindle cell components. The epithelial component was prominent and consisted of simple glands with round lumina and complex glandular structures with intraluminal bridges forming cribriform areas. The glands were lined by cuboidal to columnar cells with eosinophilic or clear cytoplasm manifesting apical apocrine-like and intraluminal eosinophilic secretions. The spindle cell component was less prominent and was composed of relatively uniform or slightly atypical spindle sells surrounding and merging focally with the glandular structures. Immunohistochemically, the tumor cells in both components were positive for vimentin, AE1/AE3, CK7, and epithelial membrane antigen. Desmin, smooth muscle actin, muscle-specific actin, CD34, and S-100 protein were all negative. SYT-SSX1 gene fusion using fluorescence in situ hybridization and RT-PCR methods was detected in both cases.
  The American Journal of dermatopathology 04/2013;
• Article: Syndrome of birt-hogg-dubé, a histopathological pitfall with similarities to tuberous sclerosis: a report of three cases.

  Philipp Spring, Florence Fellmann, Sophie Giraud, Helena Clayton, Daniel Hohl
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  ABSTRACT: : Birt-Hogg-Dubé Syndrome (BHD) is a rare condition, transmitted as an autosomal-dominant trait. The etiology is due to a mutation in the BHD gene, which encodes folliculin (FLCN), located on chromosome 17p. The skin changes observed are benign skin tumors consisting of hamartomas of the hair follicle with dermal changes. Patients with BHD have an increased risk of spontaneous pneumothorax due to rupture of lung cysts and an increased risk of kidney tumors. We report 3 new cases of BHD and discuss their clinical features, histopathological findings, and molecular diagnostics. We highlight the importance of genetic analysis to confirm the diagnosis because of the clinical pitfalls involved in establishing a diagnosis. Finally, we discuss the histopathological features in BHD and tuberous sclerosis complex and focus on their overlapping criterias. A correct diagnosis is essential as it can be life saving for patients.
  The American Journal of dermatopathology 04/2013; 35(2):241-5.
• Article: Cutaneous metastases can be the initial presenting sign of a cardiac sarcoma.

  José Fernando Val-Bernal, María Francisca Garijo
  The American Journal of dermatopathology 04/2013; 35(2):286-7.
• Article: Benign Atypical Intravascular CD30+ T-cell Proliferation: A Reactive Condition Mimicking Intravascular Lymphoma.

  Erica Riveiro-Falkenbach, María Teresa Fernández-Figueras, José Luis Rodríguez-Peralto
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  ABSTRACT: : CD30 is a transmembrane glycoprotein molecule usually expressed in activated B and T cells. Although it has been considered a reliable marker for CD30 lymphomas, reactive inflammatory disorders may contain a significant number of CD30 cells mimicking lymphoproliferative disorders clinically or histologically. Intravascular lymphoma is a rare variant of non-Hodgkin lymphoma that can involve the skin in 40% of the patients. The majority of cases show a B-cell phenotype, and only a minority of cases are of T-cell or NK-cell origin. Moreover, 2 aggressive cases of intravascular large T-cell lymphoma have been described with a CD30 phenotype. Herein, we report 2 patients with skin lesions showing an atypical intravascular CD30 T-cell proliferation. Both the patients did not present systemic disease and therefore exhibit a favorable outcome. To the best of our knowledge, this is the second report in the literature of a benign intravascular CD30 T-cell proliferation that represents an intriguing differential diagnosis for intravascular lymphoma.
  The American Journal of dermatopathology 04/2013; 35(2):143-50.
• Article: Essential thrombocythemia presenting as localized livedo reticularis.

  Ursula Pielasinski, Rosario Haro, Carlos Santonja, Heinz Kutzner, Luis Requena
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  ABSTRACT: : Essential thrombocythemia is a chronic myeloproliferative disorder characterized by a persistent and absolute increase in the peripheral platelet count (>600,000/mm) in the absence of another underlying disorder. From a clinical point of view, it is characterized by thrombotic manifestations that primarily involve the central nervous system as strokes and transient ischemic attacks and also affects other systems, causing gastrointestinal hemorrhages and arterial or venous thrombosis. Cutaneous manifestations may complicate essential thrombocythemia, but they may be a helpful guide to the diagnosis. These manifestations appear up to 22% of patients and may even be the presenting sign of the disease in up to 10% of them. We present a case of a previously healthy woman who was diagnosed with essential thrombocythemia after the onset of localized livedo reticularis. The case was immunohistochemically studied, supporting the role of the increased platelet number in the pathogenesis of the livedo reticularis lesions.
  The American Journal of dermatopathology 04/2013; 35(2):e22-5.