[Show abstract][Hide abstract] ABSTRACT: Cellular neurothekeoma is a benign lesion most commonly found on the face and upper extremities in the first two decades of life.
Retrospective clinicopathologic review of 12 examples of cellular neurothekeoma typified by prominent stromal sclerosis, a distinctive variant that we refer to as desmoplastic cellular neurothekeoma.
The mean age was 30 years (range, 3-55 years, 3 males, 9 females). The site was the head and neck in 3 cases, upper extremity in 4, lower extremity in 2, and trunk/abdomen in 3. All cases showed fascicles of slightly spindled and polygonal cells arrayed haphazardly in a prominent sclerotic background in the dermis and superficial subcutis. The cells displayed pale cytoplasm with indistinct membranes and vesicular nuclei with a single nucleolus. Lesional cells expressed NKI/C3, laminin, CD68, and CD10 and lacked expression of S-100 protein, EMA, and CD34. Clinical follow up was available on 10 cases with a mean duration of 24 months (range, 11-42 months) with no local recurrences or metastases.
The immunohistochemical staining pattern, clinical findings, and benign nature are similar to "conventional" cellular neurothekeomas. The differential diagnosis includes desmoplastic melanocytic lesions, desmoplastic spindle cell carcinoma, dermatofibroma, "immature" scar, plexiform fibrohistiocytic tumor, perineurioma, and piloleiomyoma.
[Show abstract][Hide abstract] ABSTRACT: Many complications have been reported after orf infection, including lymphadenopathy, secondary bacterial infection, and erythema multiforme. Rare associations with papulovesicular eruptions, including a bullous pemphigoid-like eruption, have also been described.
Our purpose was to clinically, histologically, and immunologically characterize two cases of orf-induced blistering disease, and to determine whether this condition represented a novel disease entity distinct from known immunobullous diseases.
Two patients were clinically described and skin biopsy specimens were collected for routine histology, direct immunofluorescence studies, and polymerase chain reaction analysis to detect orf viral DNA. Patients' sera were assessed for autoantibodies by indirect immunofluorescence studies using normal-appearing human salt-split skin, by Western blot analysis using keratinocyte extracts, dermal extracts, and recombinant type VII collagen, and immunoprecipitation studies of extracts from biosynthetically radiolabeled human keratinocytes.
Two distinctive cases of severe, diffuse blistering eruptions after orf infection are described. In one patient, orf virus DNA was detected in the inciting orf lesion, but not in blistered skin, ruling out disseminated orf infection as a cause of the blisters. In both cases, histology revealed subepidermal blisters with mixed inflammatory cell infiltrates containing neutrophils and eosinophils, direct immunofluorescence microscopy studies demonstrated IgG and C3 deposited at the dermoepidermal junctions of perilesional skin, and indirect immunofluorescence studies demonstrated circulating antibasement membrane IgG that bound the dermal side of salt-split skin. Extensive immunoblot and immunoprecipitation studies failed to reveal a consistent, identifiable autoantigen.
We describe only two cases. The autoantigen recognized by circulating autoantibodies was not identified.
Orf-induced immunobullous disease is a unique disease entity that is clinically and immunologically distinct from bullous pemphigoid, epidermolysis bullosa acquisita, and other known immunobullous conditions.
Full-text · Article · Feb 2008 · Journal of the American Academy of Dermatology
[Show abstract][Hide abstract] ABSTRACT: Clear-cell acanthoma (CCA) has been reported to be a benign epidermal neoplasm; however, several authors have suggested alternative differentiation as well as other nosologic categories, including a reactive dermatosis. Fourteen CCAs, ten tricholemmomas, and seven cases of psoriasis were reviewed with conventional microscopy, periodic acid-Schiff stains, and immunohistochemical stains. Twelve of fourteen (86%) CCAs were associated with underlying or adjacent conditions. The CCAs stained immunohistochemically in a pattern similar to normal epidermis and psoriasis. Tricholemmomas stained in a distinctly different pattern with MNF116 and NGFR/p75. These cases demonstrate CCA in settings that reflect chronic inflammation, primarily scars and stasis dermatitis, and with an immunophenotype that parallels psoriasis. These findings support the contention that CCA does not show outer follicular sheath (tricholemmal) differentiation. Furthermore, these cases lend additional support to the contention that CCA represents a psoriasiform reaction pattern, which, in appropriately taken biopsies, usually has a demonstrable associated condition. Nonetheless, the precise nosology of this phenomenon has yet to be elucidated completely.
No preview · Article · Sep 2007 · American Journal of Dermatopathology
[Show abstract][Hide abstract] ABSTRACT: The clinical distribution and character of cutaneous lupus erythematosus lesions can simulate squamous neoplasms, leading physicians to submit a shave biopsy specimen with a differential diagnosis of squamous neoplasm.
Our aim was to describe histologic features of interface dermatitis that cause difficulty in distinguishing between cutaneous lupus erythematosus and squamous neoplasia in shave biopsy specimens and to identify distinguishing criteria.
Twenty-six biopsy specimens from 10 patients initially diagnosed with squamous neoplasia that ultimately proved to be cutaneous lupus erythematosus were identified. Comparisons were made of these to 38 control biopsies of chronic cutaneous lupus erythematosus and 34 control biopsies of keratoses/carcinomas without lupus. All biopsies were scored (0 or 1: absent or present) with respect to 11 histologic criteria.
The criteria of perifollicular inflammation, follicular plugging, vacuolar interface change, compact orthokeratosis, and acrosyringeal inflammation were significantly more common in the lupus cases than in the keratoses/carcinomas controls. The mean lupus case score was 6.88, lupus control score 6.55, and keratoses/carcinomas control score 5.08.
A limited number of patients were studied. Microscopic observations and assumptions with inherent subjectivity were used in establishing the histologic scores.
Use of the criteria presented, although not absolute, should alert one to the possibility of lupus in an atypical squamous proliferation, especially in suspected squamous neoplasms that worsen or recur after therapy.
No preview · Article · Jul 2007 · Journal of the American Academy of Dermatology
[Show abstract][Hide abstract] ABSTRACT: Granular cell tumors (GCTs) are neoplasms showing nerve sheath differentiation that can arise in the skin but, to our knowledge, have not been associated with significant clear-cell morphology.
Two patients developed four separate GCTs with distinctive, diffuse clear-cell change, which completely camouflaged the primary differentiation. The morphology, histochemistry and immunohistochemistry of the lesions are described and are compared with the presence and extent of clear-cell change in 14 other cases of GCTs.
The index cases were relatively broad proliferations with uniform diffuse clear-cell change and only minimal overlying epidermal hyperplasia. Prominent lymphoid nodules were present at the periphery. These clear-cell granular tumors were positive for S-100 protein, p75, CD68, NKI/C3 and neuron-specific enolase and were negative for epithelial mucin, periodic acid-Schiff, carcinoembryonic antigen, HMB-45, Melan-A, smooth muscle actin, Leu7, synaptophysin, CD34, factor XIIIa, epithelial membrane antigen and cytokeratin. Three of the fourteen comparison cases were found to have no clear-cell change, eight showed focal clear-cell change and three showed moderate clear-cell change.
The distinctive morphology and the immunohistochemical results are discussed in the context of the differential diagnosis of clear-cell cutaneous tumors.
No preview · Article · Jun 2007 · Journal of Cutaneous Pathology
[Show abstract][Hide abstract] ABSTRACT: Self-healing juvenile cutaneous mucinosis is a rare disease affecting young people characterized by transient cutaneous lesions and sometimes mild inflammatory symptoms. The deep dermal and subcutaneous features of this disorder have not yet been well described.
The purpose of our study was to present 3 cases of self-healing juvenile cutaneous mucinosis in which the histopathologic features caused diagnostic confusion between this disorder and proliferative fasciitis.
The study includes clinical and histologic findings of 3 patients, complemented by a literature review.
The histologic descriptions of nodular lesions in self-healing juvenile cutaneous mucinosis reveal features of proliferative fasciitis, including a myxoid stroma and gangliocyte-like giant cells.
Self-healing juvenile cutaneous mucinosis is a rare condition and has not been frequently reported in medical literature. Our findings are based on the pathologic features of 3 patients.
Our findings further elucidate the histologic features of self-healing juvenile cutaneous mucinosis and expand the differential diagnosis for entities in which gangliocyte-like giant cells are noted.
Preview · Article · Jan 2007 · Journal of the American Academy of Dermatology
[Show abstract][Hide abstract] ABSTRACT: A 75-year-old woman was referred for treatment of multiple keratoacanthomas and hypertrophic lichen planus. Surgical excision was considered but was not possible given the multiplicity of the lesions. Etretinate, potent topical corticosteroids and gradient support stockings were initiated. Complete resolution was achieved in four months and oral and topical therapy was discontinued. Four months after discontinuation of all therapy there has been no recurrence.
No preview · Article · Jul 2006 · Journal of the European Academy of Dermatology and Venereology
[Show abstract][Hide abstract] ABSTRACT: The rapid evolution of digital imaging has facilitated the ability to include photomicrographs in pathology reports. Although these pictures may seem to be an informative accompaniment to the written report, there are many problems raised by the images, which are not generally recognized. These include lack of quality standards, selection of representative images, and liability implications, which are addressed by well-established legal precedent. For dermatologists there is no such thing as a casual interest in a photomicrograph on a report, for it acts to distribute a share of liability by obligating the clinician to interpret the image properly. The risk management ramifications of these unintended consequences should be strongly considered by clinicians who favor the receipt of photomicrographic images in their pathology reports.
No preview · Article · Mar 2006 · Journal of the American Academy of Dermatology
[Show abstract][Hide abstract] ABSTRACT: It is well documented that nevus cells can be found within the fibrous capsule and trabeculae of lymph nodes; however, it is less well known that nevus cells can also be found in the lymph node parenchyma. We report the findings in 13 cases of nevus cell aggregates located within the cortical and/or medullary parenchyma of lymph nodes. Seven of the 13 patients had a primary diagnosis of melanoma, three had no known malignancy, one had breast carcinoma, one had adnexal carcinoma of the skin, and one had squamous cell carcinoma of the tonsil. Of the seven patients with melanoma, four had axillary lymph node dissections and three had inguinal lymph node dissections. The patient with adnexal carcinoma had metastatic carcinoma in 14 of 20 lymph nodes that had been dissected; one of them also had intraparenchymal nevus cells. The patient with squamous cell carcinoma of the tonsil had an intraparenchymal nevus cell aggregate in one of the 21 dissected lymph nodes; all 21 were negative for carcinoma. Nests of intraparenchymal nevus cells ranged from clusters of only a few cells up to 2.1-mm aggregates. No mitotic figures, prominent nucleoli, or lymphatic-vascular invasion were detected in any of the melanocytic aggregates. The melanocytic cells of the nevus cell aggregates expressed S-100 protein and/or MART-1 but not gp100 protein (HMB-45). Less than 1% of the nevus cells expressed Ki-67. The purpose of this study was to draw attention to the finding of nevus cells in the parenchyma of lymph nodes and to alert pathologists to this as a potential diagnostic pitfall, especially in patients with concurrent melanoma or carcinoma. Awareness that nevus cells can be present in nodal parenchyma, analysis of their morphologic features (including comparison with any previous or existing melanoma or carcinoma), and immunophenotyping will help pathologists to establish the correct diagnosis in most instances.
No preview · Article · Jun 2003 · American Journal of Surgical Pathology
[Show abstract][Hide abstract] ABSTRACT: Microtubule associated protein 2 (MAP-2) is one of a group of polypeptides that are an integral component of the microtubular cytoskeletal structure of the central and peripheral nervous system. During the course of another investigation that utilized immunohistochemistry, MAP-2 expression was observed in the hair follicle, almost exclusively in the innermost layer of the outer root sheath of the anagen follicle. This innermost layer, the so-called companion layer, has unique properties that clearly distinguish it from the rest of the outer root sheath. Among these are diminished glycogenation and an intimate association with the Henle's layer, which it directly apposes. Numerous intercellular connections exist between the companion layer and Henle's layer and, in fact, the companion layer accompanies Henle's layer during its vertical ascent in the follicle. Circumferentially oriented keratin filaments have also been demonstrated between the companion layer and Henle's layer, apparently providing structural support to the inner root sheath. Experimentally, disturbances in the keratin filaments of the companion layer in animals ultimately results in destruction of the hair follicle and an alopecia.
Immunohistochemical studies for MAP-2 were performed on 25 additional paraffin-embedded scalp specimens using standard techniques. Because of the parallels between the follicle and nail, MAP-2 expression in the nail unit was also investigated in three specimens.
The presence of MAP-2 in the companion layer was confirmed in all cases. Intense MAP-2 expression in the companion layer begins at the B-fringe (the start of the keratogenous zone with cornification of the Henle's layer of the inner sheath) and extends to the level of the isthmus where the inner root sheath exfoliates. MAP-2 is also expressed in the upper layers of the nail matrix.
The expression of MAP-2 almost exclusively in the companion layer is probably related to the unique cytoskeletal structure of this microanatomic layer. Since experimental evidence has shown that the cell cytoskeleton is important to the integrity of the hair follicle, it is probable that MAP-2 expression is also important and disturbances in its expression could play a role in the pathogenesis of some alopecias. MAP-2 may play a similar role in the nail matrix.
No preview · Article · Nov 2002 · Journal of Cutaneous Pathology
[Show abstract][Hide abstract] ABSTRACT: Primary signet ring cell carcinoma of the eyelid is a rare neoplasm with less than ten cases described. This report details another case, which shows further parallels to lobular carcinoma of the breast, and reviews the literature on this subject. A 73-year-old white female presented with diffuse induration of her left eyelids. Histopathology revealed a delicate infiltrate of epithelial cells scattered throughout the lid stroma in a non-destructive pattern. The cells were relatively monomorphous and showed only mild atypia and rare mitotic figures. Many had slightly granular amphophilic cytoplasms, others showed distinct signet ring cell morphology, and all were strongly positive for epithelial mucin. Immunomicroscopy showed strong reactivity for estrogen receptor (ER), progesterone receptor (PR) and gross cystic disease fluid protein-15 (GCDFP-15), and was negative for Her-2/neu (erb-2) and cytokeratin 20. An extensive workup for other primary sites was negative. Orbital exenteration showed extensive involvement of both lids and soft tissue, including diffuse muscle and lacrimal gland infiltration. In the breast, signet ring cell carcinoma is considered a variant of lobular carcinoma. The delicate infiltrating pattern in our case and the ER+, PR+, GCDFP-15+, Her-2/neu-phenotype further strengthen this analogy. Together, these data also support apocrine differentiation of primary eyelid signet ring cell carcinoma.
No preview · Article · Nov 2001 · American Journal of Dermatopathology
[Show abstract][Hide abstract] ABSTRACT: Cutaneous melanocytic neoplasms are known to acquire variable characteristics of neural crest differentiation. Melanocytic nevus cells in the dermis and desmoplastic melanomas often display characteristics of nerve sheath differentiation. The extent and nature of neuronal differentiation characteristics displayed by primary and metastatic melanoma cells are not well understood. Here, we describe induction of a juvenile isoform of microtubule-associated protein 2 (MAP-2c) in cultured metastatic melanoma cells by the differentiation inducer hexamethylene bisacetamide. Up-regulation of this MAP-2 isoform, a marker for immature neurons, is accompanied by extended dendritic morphology and down-regulation of tyrosinase-related protein 1 (TYRP1/gp75), a melanocyte differentiation marker. In a panel of cell lines that represent melanoma tumor progression, MAP-2c mRNA and the corresponding approximately 70-kd protein could be detected predominantly in primary melanomas. Immunohistochemical analysis of 61 benign and malignant melanocytic lesions showed abundant expression of MAP-2 protein in melanocytic nevi and in the in situ and invasive components of primary melanoma, but only focal heterogeneous expression in a few metastatic melanomas. In contrast, MAP-2-positive dermal nevus cells and the invasive cells of primary melanomas were TYRP1-negative. This reciprocal staining pattern in vivo is similar to the in vitro observation that induction of the neuronal marker MAP-2 in metastatic melanoma cells is accompanied by selective extinction of the melanocytic marker TYRP1. Our data show that neoplastic melanocytes, particularly at early stages, retain the plasticity to express the neuron-specific marker MAP-2. These observations are consistent with the premise that both benign and malignant melanocytes in the dermis can express markers of neuronal differentiation.
Full-text · Article · Jul 2001 · American Journal Of Pathology
[Show abstract][Hide abstract] ABSTRACT: The following case report details a 53-year-old man with a 6-year history of the benign cutaneous or skin-limited form of Degos' disease. Clinically, the patient demonstrated a diffuse eruption of papules on the upper trunk and arms. Many papules demonstrated the classic porcelain-white centers characteristic of Degos' disease, but others exhibited different clinical morphologies that corresponded to the evolutionary stages of papules originally described by Degos. Over the course of several clinic visits, the patient underwent a total of 5 punch biopsies, the histologies of which were correlated with their clinical morphologies. Early papules were skin-colored and demonstrated a superficial and deep perivascular, periadnexal, and perineural chronic inflammatory cell infiltrate associated with interstitial mucin deposition. The overlying epidermis showed a mild vacuolar interface reaction and the histologic appearances at this early stage resembled tumid lupus erythematosus. Fully developed papules were raised with umbilicated porcelain-white centers and a surrounding erythematous rim. Histologically these exhibited a prominent interface reaction with squamatization of the dermo-epidermal junction, melanin incontinence, epidermal atrophy, and a developing zone of papillary dermal sclerosis that resembled the early stages of lichen sclerosus et atrophicus in miniature. These interface reactions were invariably confined to the central portion of the punch biopsy specimen, corresponding to the central porcelain-white area seen clinically. Additional features of fully developed papules included a prominent lymphocytic vasculitis affecting venules, a mild periadnexal infiltrate of neutrophils and/or eosinophils, and interstitial mucin deposition. In late-stage papules, the porcelain-white areas were better developed and the lesion flattened. Histologically, the degree of inflammation was generally sparse and the overall picture mirrored the classic histologic description of Degos' disease with a central roughly wedge-shaped zone of sclerosis surmounted by an atrophic epidermis and hyperkeratotic compact stratum corneum. These late-stage papules closely resembled a miniaturized version of fully developed lichen sclerosus et atrophicus confined to the center of the punch biopsy specimen.
No preview · Article · Apr 2001 · American Journal of Dermatopathology
[Show abstract][Hide abstract] ABSTRACT: Rudimentary meningocele, a malformation in which meningothelial elements are present in the skin and subcutaneous tissue, has been described in the past under a variety of different terms and has also been referred to as cutaneous meningioma. There has been debate as to whether rudimentary meningocele is an atretic form of meningocele or results from growth of meningeal cells displaced along cutaneous nerves
We reviewed the clinical, histological, and immunohistochemical characteristics of rudimentary meningocele in an attempt to assess the most likely pathologic mechanism for it.
Thirteen children with rudimentary meningocele.
Medical records were reviewed and histopathologic examination as well as immunohistochemistry studies were performed for each case. A panel of immunoperoxidase reagents (EMA, CD31, CD34, CD57, S-100, and CAM 5.2) was used to assess lineage and to confirm the meningothelial nature of these lesions.
Recent evidence indicating a multisite closure of the neural tube in humans suggests that classic meningocele and rudimentary meningocele are on a continuous spectrum.
Rudimentary meningocele seems to be a remnant of a neural tube defect in which abnormal attachment of the developing neural tube to skin (comparable to that in classic meningocele) could explain the presence of ectopic meningeal tissue. In the majority of cases, no underlying bony defect or communication to the meninges could be detected. However, in light of the probable pathogenesis, imaging studies to exclude any communication to the central nervous system should precede any invasive evaluation or intervention.
No preview · Article · Feb 2001 · Archives of Dermatology
[Show abstract][Hide abstract] ABSTRACT: Current recommendations for biopsy of a pigmented skin lesion suspected of being melanoma include complete excision when possible. Because benign pigmented lesions do not warrant excisional biopsy, especially when they are large and/or on cosmetically sensitive sites, incisional biopsy is desirable. For such lesions we recommend a fusiform incisional biopsy. This tissue sampling technique not only yields an excellent cosmetic outcome, but also provides the pathologist with an optimal biopsy specimen in which he/she can assess the symmetry, circumscription, breadth, and depth of the lesion.
No preview · Article · Aug 2000 · Dermatologic Surgery
[Show abstract][Hide abstract] ABSTRACT: Mohs micrographic surgery (MMS) modified by the use of tangential, formalin-fixed, paraffin-embedded histologic specimens is advantageous in treating selected skin neoplasms.
To review the use of our experience with a modification of MMS to treat lentigo maligna melanoma (LMM), lentigo maligna (LM) and other melanoma in situ (MIS) lesions, dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and angiosarcoma.
Our experience utilizing a modification of MMS in the treatment of 77 patients with LM or other MIS, 23 patients with LMM, 11 patients with DFSP, 1 patient with AFX, and 1 patient with angiosarcoma was reviewed. Length of follow-up and rate of recurrence were examined. A literature review of this pertinent modification of the Mohs technique was performed.
One hundred fourteen patients underwent MMS for melanocytic (LM, MIS, LMM), spindle cell (DFSP, AFX), and vascular malignant neoplasms. One patient developed locally recurrent LM and one patient with LMM developed satellite metastasis. Regional lymph node metastasis occurred in one patient with LMM and in a patient with angiosarcoma.
The use of Mohs micrographic surgery in conjunction with rush formalin-fixed, paraffin-embedded tangential histologic sections provides the accuracy and tissue conservation of the Mohs procedure while ensuring more confident interpretation of histology in cases of lentigo maligna, lentigo maligna melanoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, and angiosarcoma.
No preview · Article · Aug 2000 · Dermatologic Surgery
[Show abstract][Hide abstract] ABSTRACT: Telomerase is an essential enzyme for maintaining the telomeres of chromosomes and thereby enhancing the sustained replication of cells. Because atherosclerosis and restenosis are characterized by cellular proliferation, we determined whether telomerase enzyme activity was present in coronary artery tissue from 23 patients undergoing directional coronary atherectomy. Telomerase activity was determined from detergent lysates of the atherectomy tissue using an enzyme-linked immunoadsorbent assay (ELISA)-based modification of the Telomere Repeat Amplification Protocol. The presence of telomerase activity was correlated with the occurrence of coronary artery restenosis. Eight of the 23 samples (35%) were positive for telomerase. Seventeen of the 23 patients had adequate clinical follow-up to judge restenosis status. Of these, 7 had restenosis and 5 of these 7 had detectable telomerase. Of the 10 patients without restenosis, 8 were telomerase negative (p ≤ 0.05). We have shown, for the first time, that telomerase is found in 35% of atherosclerotic tissues. There was a strong trend toward an association between telomerase presence and restenosis in patients for whom follow-up data were available. The presence of telomerase in atherosclerotic tissue may enable a robust, sustained cellular proliferation in response to vascular injury that culminates in restenosis.
No preview · Article · Mar 2000 · Journal of Anti-Aging Medicine