Tien Anh Tran

Cellular blue nevus with atypia (atypical cellular blue nevus): a clinicopathologic study of nine cases

Atypical cellular blue nevus (ACBN) has clinicopathologic features intermediate between typical cellular blue nevus (CBN) and the rare malignant blue nevus (MBN)/malignant melanoma (MM) arising in a CBN. Herein we report 9 cases of ACBN. The patients were caucasian (6 females and 3 males) with a mean and median age of 47/51 years. Two patients complained of recent changes and about half of these tumors were located on the buttocks or scalp, averaging 1.5 cm in diameter. Histologically, they were characterized by architectural atypia (infiltrative margin and/or asymmetry) and/or cytologic atypia (hypercellularity, nuclear pleomorphism, hyperchromasia, mitotic figures, and/or necrosis). Assessment of the expression of 3 tissue markers demonstrated rare solitary cell staining with oncogene product bcl‐2, and a proliferative index of 23±19 and 39±30 cells/10 high power field with antibodies to PCNA and Mib‐1, respectively. No significant differences were detected comparing the above levels of expression to a control group of 15 CBN; however, ACBNs tended to show a higher proliferative index by PCNA and Mib‐1 as well as a significantly higher mitotic rate (1/10 HPF vs. 0; p=0.001). Analysis of DNA content showed DNA anetiploidy in both groups. Follow‐up data on 9 of 9 patients showed 1 patient dead without disease and 8 alive without disease (mean/median follow‐up 42/32 months, range 15‐96 months). No patient during this follow‐up time has experienced either a local recurrence or lymph node or visceral metastasis. These findings highlight the close resemblance of ACBN to the natural history of CBN. Nevertheless, many of the distinguishing histologic features of ACBN are also those of MBN. Because of these intermediate clinicopathologic features, ACBN warrant close scrutiny and long‐term follow‐up.

Cutaneous carcinosarcoma: adnexal vs. epidermal types define high‐ and low‐risk tumors. Results of a meta‐analysis

Objective:  We report four cases of cutaneous carcinosarcoma (CS) and perform a meta‐analysis of the cutaneous CS literature.

Localized lymphedema (elephantiasis): a case series and review of the literature

Background:  Lymphedema typically affects a whole limb. Rarely, lymphedema can present as a circumscribed plaque or an isolated skin tumor.

Otophyma: a case report and review of the literature of lymphedema (elephantiasis) of the ear.

Phymas (swellings, masses, or bulbs) are considered the end-stage of rosacea and mostly affect the nose (rhinophyma), and rarely involve the chin (gnatophyma), the cheek (metophyma), eyelids (blepharophyma), or ears (otophyma). Herein, we report the case of a 57-year-old man who developed unilateral enlargement of his left ear over 2 years. Biopsy revealed changes of rosaceous lymphedema associated with Demodex infestation. Corticosteroid and minocycline therapies resulted in partial reduction of the ear enlargement. Literature review examining for cases of lymphedema (elephantiasis) of the ear revealed that chronic inflammatory disorders (rosacea (most frequent), psoriasis, eczema), bacterial cellulitis (erysipelas), pediculosis, trauma, and primary (congenital) lymphedema can all lead to localized, lymphedematous enlargement of the ear. Depending on the severity, medical treatment directed at the inflammatory condition for mild, diffuse enlargement to surgical debulking for extensive diffuse enlargement or tumor formation can improve the signs and symptoms of otophyma. Decreased immune surveillance secondary to rosaceous lymphedema may explain why Demodex infestation is common in rosacea and support the suspicion that phymatous skin is predisposed to skin cancer development.

Chromosome 17 Aneusomy Detected by Fluorescence in Situ Hybridization in Vulvar Squamous Cell Carcinomas and Synchronous Vulvar Skin

Vulvar squamous cell carcinoma (SCC) affects a spectrum of women with granulomatous vulvar diseases, human papillomavirus (HPV) infections, and chronic inflammatory vulvar dermatoses. To determine whether there is evidence of chromosomal instability occurring in synchronous skin surrounding vulvar SCCs, we investigated abnormalities in chromosome 17 copy number. Samples of SCC, vulvar intraepithelial neoplasia (VIN), and surrounding vulvar skin were obtained from all vulvar excisions performed for squamous neoplasia at Albany Medical College from 1996 to 1997. Histological categorization, fluorescent in situ hybridization (FISH) for the alpha satellite region of chromosome 17, DNA content by image analysis, and Ki-67 labeling were evaluated. Controls of normal vulvar skin not associated with cancer were used for comparison. One hundred ten specimens were obtained from 33 patients with either SCC or VIN 3 and consisted of 49 neoplastic, 52 nonneoplastic, and 9 histologically normal vulvar skin samples. The majority of SCCs (88%) and a minority (18%) of VIN 3 excisions were associated with lichen sclerosus. Normal vulvar skin controls did not exhibit chromosome 17 polysomy (cells with more than four FISH signals), whereas 56% of normal vulvar skin associated with cancer did. Moreover, the frequency of polysomy significantly increased as the histological classification progressed from normal to inflammatory to neoplastic lesions. The largest mean value and variance for chromosome 17 copy number was identified in SCCs (2.4 +/- 1.0) with intermediate values identified, in decreasing order, for SCC in situ (2.1 +/- 1.0), VIN 2 (2.1 +/- 0.8), lichen sclerosus (2.0 +/- 0.5), lichen simplex chronicus (1.9 +/- 0.4), and normal skin associated with SCC (1.8 +/- 0.4) compared with control vulvar skin (1.5 +/- 0. 05). Concordance of chromosome 17 aneusomy between cancers and synchronous skin lesions was found in 48% of patients. Loss of chromosome 17 was identified 5% of all samples and was significantly associated with women with SCC in situ (HPV-related). Both DNA content and Ki-67 labeling positively and significantly correlated with mean chromosome 17 copy number (r = 0.1, P: = 0.007). A high degree of genetic instability (aneuploidy) occurs in the skin surrounding vulvar carcinomas. As these events could be detected in histologically normal skin and inflammatory lesions (lichen sclerosus), chromosomal abnormalities may be a driving force in the early stages of carcinogenesis. Differences in chromosomal patterns (loss or gain) support the concept of at least two pathways in vulvar carcinogenesis.

Paraffin section immunophenotype of cutaneous and extracutaneous mast cell disease: comparison to other hematopoietic neoplasms.

Mast cell disease (MCD) is a rare proliferation that may be easily confused with other hematopoietic tumors. Several paraffin section antibodies immunoreact with mast cells but most are not specific. Tryptase, a specific marker of mast cells, may not be cost-effective to maintain in a laboratory because of the rarity of these lesions. This study was undertaken to assess the immunoreactivity of MCD and attempt to select a limited antibody panel for diagnosing MCD among hematopoietic tumors that morphologically mimic MCD. Immunophenotyping of cutaneous ( 10 cases) and extracutaneous (18 cases) MCD, as well as 94 other hematopoietic neoplasms, was performed on paraffin sections. All cases of MCD showed strong and diffuse positivity for CD68 and tryptase. In the vast majority of the cases, the mast cells were also positive for CD117 (27 of 28) and CD43 (25 of 27). Four cases (40%) of cutaneous MCD demonstrated a subpopulation of mast cells expressing myeloperoxidase (MPX), whereas all extracutaneous MCD were negative for MPX. Two (40%) extramedullary myeloid tumors (EMT) expressed CD43, CD68, CD 117, and MPX, but none expressed tryptase. CD43, CD68, CD117, and tryptase were expressed by 25%, 1%, 15%, and 1%, respectively, of all B-cell lymphoid neoplasms, and none expressed more than one of these four antigens. We conclude that (1) cutaneous MCDs may demonstrate a subpopulation of MPX antigen expressing tumor cells and may be confused with cutaneous involvement by myeloid leukemia if other antibodies are not used; (2) tryptase is the most specific mast cell marker among the antibodies studied; and, (3) the detection of tryptase, together with CD68, CD117, and usually CD43, is unique to MCD among hematopoietic tumors.

Topoisomerase II-alpha expression in melanocytic nevi and malignant melanoma.

Malignant melanoma (MM) is considered to be a chemotherapy‐refractory tumor. New anti‐cancer drugs (e.g. etoposide) that target DNA topoisomerases (e.g. topoisomerase II‐alpha (topo IIα)) show activity against a wide variety of solid tumors. In this study, we investigated the frequency and rate of labeling for topo IIα in 163 MMs (primary and metastatic) and 67 melanocytic nevi to determine whether topo IIα expression is elevated in MM. Primary MM exhibited significantly more frequent topo IIα expression compared to benign nevi (86% vs. 56%, p=0.0001). The rate of topo IIα labeling in dysplastic melanocytic nevi, radial growth phase MM, vertical growth phase MM and metastatic MM revealed significant differences amongst groups and a positive covariance with advancing stage (means: 0.3, 0.5, 5, and 8 ‘+’ cells/hpf, respectively; r=0.3, all p≤0.02). Topo IIα labeling significantly correlated with increasing mitotic activity, depth of invasion and Clarks level, diminishing tumor infiltrating lymphocytes, and poor outcome (all p≤0.01) in primary MM. For metastatic MM, a minority (30%) exhibited marked elevation of topo IIα expression. These findings indicate topo IIα as a potential therapeutic target and marker for MM. Immunohistochemical analysis of disseminated MM may allow for correlation with clinical response and enable selection of candidates sensitive for specific chemotherapy ( Note ).

The Evolution of Osseous Metaplasia in Localized Cutaneous Nephrogenic Systemic Fibrosis: A Case Report

Gadolinium (Gd) is associated with nephrogenic systemic fibrosis (NSF), a severe disorder mimicking scleroderma with involvement of the skin, lungs, heart, liver, and muscles. There is strong evidence that specific Gd-containing contrast agents (GCCAs) used in magnetic resonance imaging can cause NSF when administered to patients with chronic kidney disease. We present the 8-year history of cutaneous NSF with osseous metaplasia that occurred in a 56-year-old man with dialysis-dependent renal failure who was exposed to GCCA [gadopentate dimeglumine (Magnevist; Bayer Schering Pharma AG, Pittsburgh, PA)]. Three months after exposure to GCCA, he developed pruritic, pigmented patches that slowly coalesced and darkened over 8 years. Although not recognized at onset, skin biopsy showed typical histology of NSF affecting the entire dermis: CD34+/procollagen I+ spindle cells associated with fibrosis. Biopsy performed 6 years later showed superficial scar-like fibrosis that was CD34/procollagen I− and had numerous elastocollagenous balls (refractile elastic fibers surrounded by coarse collagen). Biopsy 7 years later showed the superimposition of osseous metaplasia on elastocollagenous balls. Both of these later biopsies had typical NSF histology affecting the deep dermis and subcutis. Over time, there was progressive diminishment of CD34+ and procollagen I+ cells and an increase in FXIIIa+ and CD68+ cells. Scanning electron microscopy and energy-dispersive x-ray spectroscopy showed Gd deposits in all areas of typical NSF histology but not in the regions of scar-like fibrosis, elastocollagenous balls, or osseous metaplasia. We suspect that the later changes may represent a late, involuting stage of NSF.

Plasmacytoid squamous cell carcinoma of the vulva.

Although neoplastic cells with a plasmacytoid appearance have been reported in a variety of tumors, to the best of our knowledge, a plasmacytoid squamous cell carcinoma (SCC) of the vulva or skin has heretofore not been described. We document the case of a 92-year-old female patient with a history of multiple excisions for vulvar verrucous and SCCs, who presented with a 3-cm, symptomatic, polypoid mass of the left upper vulva. Histologically, sheets of dyscohesive relatively monotonous plasmacytoid and spindle cells were found dispersed throughout the dermis. The neoplastic cells expressed cytokeratins AE3, 5/6, and 903, p63, and the plasma cell markers CD138 (syndecan-1) and VS38. The neoplastic cells did not label with S-100 protein, Melan-A, smooth muscle actin, desmin, Kappa and Lambda light chains, epithelial membrane antigen, MOC-31, uroplakin III, thrombomodulin, and E-cadherin. Based on the tumor location, morphology, and immunohistochemical results, the diagnosis of plasmacytoid SCC of the vulva was rendered. Six months after complete excision, she developed regional inguinal lymph node and pulmonary metastases and died. Like other plasmacytoid malignancies, vulvar plasmacytoid SCC is a rare and likely aggressive variant of SCC, which can pose significant diagnostic challenges. Squamous cell carcinoma should also be considered in the differential diagnosis of neoplasms with plasmacytoid cytology. To correctly classify plasmacytoid malignancies, a wide panel of immunohistochemical markers must be used.

Ileostomy-associated chronic papillomatous dermatitis showing nevus sebaceous-like hyperplasia, HPV 16 infection, and lymphedema: a case report and literature review of ostomy-associated reactive epidermal hyperplasias.

Abstract:Chronic papillomatous dermatitis (CPD) is a stoma site complication due to chronic irritant contact dermatitis. Papillomatosis can also arise in the setting of Human Papillomavirus (HPV) infection or chronic lymphedema (elephantiasis). Herein, we report the case of a 57-year-old female who presented with a papillomatous growth surrounding a loop ileostomy suspected to be recurrent ovarian serous carcinoma. Excisional biopsy demonstrated nevus sebaceous (NS)–like organoid hyperplasia with koilocytes overlying a dermal scar that exhibited lymphangiectases. Polymerase chain reaction and sequencing for HPV DNA detected HPV 16. In situ hybridization for high-risk HPV DNA showed punctate nuclear pattern in the keratinocytes populating the NS-like hyperplasia indicating integrated HPV 16 DNA. No recurrence has been observed 11 months postexcision. Reports of CPD have documented a spectrum of reactive epidermal hyperplasias including pseudoepitheliomatous, verrucous, papillomatous, syringofibroadenomatous, and rudimentary follicular hyperplasias. HPV DNA has been detected in 3 of 4 CDP cases tested to date and in authentic NS. We postulate that localized lymphedema secondary to scarring coupled with chronic epidermal irritation and inflammation allowed for latent HPV infection to manifest as CPD with NS-like cutaneous hyperplasia.