Merkel cell carcinoma with partial B-cell blastic immunophenotype: a potential mimic of cutaneous richter transformation in a patient with chronic lymphocytic lymphoma.

Merkel cell polyomavirus (MCPyV) is a DNA virus whose pathogenic mechanisms in Merkel cell carcinoma (MCC) are still being unraveled. Emerging reports of an association between MCPyV and chronic lymphocytic lymphoma (CLL) have begun to broaden our understanding of the oncogenic mechanisms of this virus and the known association between these 2 malignancies. Herein, we report a case of MCC demonstrating a B-cell immunophenotype arising in a patient with CLL being treated with rituximab. In this context, we discuss the differential diagnostic considerations, especially with cutaneous Richter transformation (diffuse large B-cell lymphoma). We also assessed for the presence of MCPyV in both the patient's MCC and the CLL. Finally, we provide a large meta-analysis of patients with CLL and MCC. Patients with both MCC and CLL have a dismal prognosis, with greater than 50% overall mortality within the first year and a half after MCC diagnosis.

Vulvar inflammatory dermatoses: an update and review.

Currently, urogenital complaints are among the most common problems encountered by family practitioners, gynecologists, and dermatologists. In response to the intricacy of vulvar disorders, the International Society for the Study of Vulvovaginal Disease was created to facilitate the exchange between clinicians and pathologists involved in the care of these patients. Recent classifications for inflammatory disorders and intraepithelial neoplasm have been proposed. In addition, vulvar skin biopsies are the most common source of intradepartmental consultation during dermatopathology sign-out. The purpose of this article is to review the various inflammatory dermatoses of the vulva and to update readers with new advances regarding these entities.

Dermatopathology of the foreskin: an institutional experience of over 400 cases.

BACKGROUND: Diseases of the foreskin may manifest with an array of pathologic findings, including potentially under-recognized dermatologic conditions. Herein, we summarize an institutional experience in foreskin dermatopathology. METHODS: Diagnoses rendered on foreskin specimens between 1982 and April 2009 were obtained through a computer-based keyword search. Cases given normal, non-specific or descriptive diagnoses were reviewed by a dermatopathologist. RESULTS: Keyword search yielded 414 foreskin diagnoses. Interpretations included normal foreskin (n = 131), benign lesions (n = 262) and malignant/dysplastic entities (n = 21). Of 353 cases given normal, descriptive or non-specific diagnoses, 334 were reviewed. Of reviewed cases, 209 (63%) were given more specific diagnoses [e.g. spongiotic dermatitis (n = 115), lichen sclerosus et atrophicus (LSA; n = 41), interface/lichenoid dermatitis (n = 26), psoriasiform dermatitis (n = 7)]. Discrepancy between the clinical and pathologic impression was frequently noted (n = 77). CONCLUSIONS: This study shows benign inflammatory lesions represent the most frequent foreskin pathology. When possible, specific diagnoses should be rendered, as accurate classification may be of clinical importance. There is an abundance of recent literature on the role of circumcision in disease prevention, and this topic is explored. We discuss the theoretical possibility that foreskin inflammation compromises the mucosal/epithelial barrier, thus playing a role in disease transmission.

Anaplastic lymphoma kinase (ALK1) immunohistochemistry in diagnostic dermatopathology; an update.

The use of anaplastic lymphoma kinase antibodies (ALK1) as a diagnostic aid has expanded since becoming a routinely available immunohistochemical stain. Because the skin may be the site of a wide variety of hematolymphoid and fibroblastic proliferations, dermatopathologists commonly use ALK1 as part of a broader staining panel in diagnosing soft tissue and cutaneous hematolymphoid neoplasms. Furthermore, new entities and differential diagnostic contexts are emerging, which broaden the utility of ALK1 immunohistochemistry. We review the expanding role of ALK1 immunohistochemistry in contemporary dermatopathology.

Vulvar vascular tumors: a clinicopathologic study of 85 patients.

The subepidermal hormonally sensitive tissue of the vulva is anatomically unique and may give rise to a wide variety of vascular tumors. As a consequence, classifying vulvar vascular lesions has been challenging due both to the wide variety of lesions that may be encountered and the heterogeneity in reporting across several disciplines. The purpose of this study is to present an institutional experience of vulvar vascular lesions. Overall, 85 patients were identified over a 26-year period. Vascular lesions belonging to the following classes included (n, %total) benign vascular tumors (32, 38%), dilatations of preexisting vessels (31, 36%), hyperplasia/reactive (7, 8%), tumors with significant vascular component (11, 13%), malformations (3, 4%), and malignant vascular tumors (1, 1%). Two reaction patterns based on vulvar lymphatic pathology were identified: one is a stromal dominant pattern and the other is a vascular dominant pattern. Vulvar vascular malformations and true vascular malignancies, although rare, may have associated high morbidity. To accurately classify vulvar lymphatic lesions, the pathologist must carefully consider the patient's clinical history taking into account features such as preexisting lymphedema.

Signet ring cell primary cutaneous CD30+ lymphoproliferative disorder presenting as a monomorphic T-cell posttransplant lymphoproliferative disease.

T-cell posttransplant lymphoproliferative disorders are rare, with peripheral T-cell lymphoma not otherwise specified being the most common type. Although cases of the signet ring cell variant of primary cutaneous CD30+ lymphoproliferative disorder have been reported, such cases have not been described in the posttransplant setting. We describe a case with emphasis on the special contextual differential diagnostic considerations.

Primary cutaneous, composite, Epstein-Barr virus-associated, diffuse large B-cell lymphoma and peripheral T-cell lymphoma.

T-cell lymphomas have a broad spectrum of cutaneous involvement. Several subtypes of T-cell lymphomas are associated with Epstein-Barr virus (EBV)-driven lymphoproliferative processes. We present a case of a composite, primary, cutaneous, EBV-associated, diffuse, large B-cell lymphoma and mature T-cell lymphoma occurring in a patient with Klinefelter karyotype (47, XXY). The patient had a characteristic clinical course of a systemic mature T-cell lymphoma before the presentation of the composite, primary, EBV-associated, diffuse, large B-cell lymphoma. Although similar cases have been described in extracutaneous locations, we believe that this is the first description with a primary cutaneous presentation.

Vulvar manifestations of Crohn's disease.

Crohn's disease is an inflammatory bowel disorder with several well-known extraintestinal manifestations, such as erythema nodosum, uveitis, and arthritis. Less commonly observed are vulvar manifestations, which have primarily been discussed in case reports or small case series. These cases generally highlight patients with histopathology limited to noncaseating granulomas. As these histological findings are identified in bowel biopsies from only approximately 50% of patients with gastrointestinal Crohn's disease, there is likely an under-recognition and underdiagnosis of vulvar lesions as Crohn's disease manifestations. We describe the largest case series to date involving patients with vulvar Crohn's disease, discuss the varied clinical presentations, and describe the histopathological findings, which include noncaseating granulomas, ulcerations, lymphatic lesions, and even dysplasia and carcinoma. Our findings underscore the importance of keeping vulvar Crohn's disease on the differential diagnosis when faced with a range of vulvar symptoms and suggest that regular gynecological surveillance in patients with Crohn's disease may be of benefit.

Metastatic vs primary malignant neoplasms affecting the umbilicus: clinicopathologic features of 77 tumors.

Periumbilical skin is unique due to its proximity to intra-abdominal and pelvic structures. In addition to primary skin malignancies, it is a site often involved with metastatic disease. We reviewed the clinical and pathologic features of 77 umbilical malignancies occurring at our institution since 1988. Seventy-seven patients were identified (female/male ratio, 4.1:1.0) with the average age for women being 63 years and 55 years for men. Eighty-eight percent of malignancies originated outside the umbilicus and 12% were primary skin tumors. Fifty-eight (85%) patients with metastatic tumors had umbilical involvement from a known primary vs 10 (15%) with unknown primaries. Nine patients with metastatic tumors to the umbilicus would present with solitary umbilical involvement. Of these patients, 56% would not have a primary site assigned to their metastatic disease. In women, the 3 most common primary sites were the ovary, endometrium, and pancreatobiliary tree, whereas for men, it was the genitourinary tract, pancreatobiliary tree, and the gastrointestinal tract. Of the primary umbilical malignancies, 44% of patients were male and 56% female. Malignant melanoma was the most common primary umbilical malignancy. In summary, women are more likely than men to have malignant tumors affecting the umbilicus. Overall, the most likely primary site of a metastatic tumor to the umbilicus is the genitourinary tract. Rarely, patients present with metastatic tumors to the umbilicus, and most of these patients will not have a primary site of tumor origin assigned.

Hematolymphoid malignancies with intraocular intravascular involvement: report of 2 cases.

The interaction between the endothelium and malignant hematolymphoid cells within vessels of the eye can result in focal or diffuse intravascular pathology. As a result, correlation of these findings with specific clinical and ophthalmologic features can vary. We review the ophthalmic findings in two cases of hematolymphoid malignancies limited to the intravascular space and review published literature on this topic. In cases of intravascular large B-cell lymphoma, underexpression of ß1-integrin and intercellular adhesion molecule-1 by the cells of intravascular large B-cell lymphoma results in diffuse ocular vascular involvement. The widespread degree of intravascular involvement correlates with clinical ophthalmologic findings and may lead to retinal and choroidal detachment that is observed postmortem. Conversely, in the context of acute leukemia, induced overexpression of certain adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) in the endothelium of certain vascular beds may result in leukostasis with only selective (choroidal) ocular vessel involvement. As a result of only focal vascular activation and adhesion in the orbit, the gross findings in these cases are minimal and may not correlate with clinical ophthalmologic findings.

Osteosarcoma after radiotherapy for prostate cancer.

Postradiation sarcomas are long-term complications of radiation treatment of various forms of cancer. Osteosarcoma, specifically, occurring in patients with a history of prostate cancer is rare; but with high-dose radiotherapy now an accepted standard of care for localized prostate adenocarcinoma, it should be considered in the clinical setting of patients presenting with potential remote disease relapse. We describe an osteosarcoma of the pubic ramus in a patient previously treated 10 years prior with radiation therapy for prostate cancer. Because of the long latency period, the appearance of lytic bone lesions with soft tissue components in pelvic bony structures may mimic recurrent/metastatic prostate adenocarcinoma. The prognosis of patients developing osteosarcoma after radiotherapy for prostate cancer is similar to other radiation-induced osteosarcomas occurring in the axial skeleton, with a 50% overall mortality within the first year after diagnosis.

Cutaneous lupus erythematosus of the eyelid as a mimic of squamous epithelial malignancies: a clinicopathologic study of 9 cases.

PURPOSE: To describe 9 cases of chronic cutaneous lupus of the eyelid, its potential similarities with squamous epithelial malignancies, and clinical and histopathologic features that assist in distinguishing lupus from epidermal neoplasia. METHODS: The authors identified and reviewed 9 cases of cutaneous lupus involving the eyelid at their institutions since 1991. Published cases of cutaneous lupus involving the eyelid were identified using Ovid MEDLINE and PubMed and references within the articles. RESULTS: The average patient age at presentation was 52 years old (range 33-89) with a female-to-male ratio of 8:1. The right lower eyelid was the most commonly affected location, with 44% of the cases occurring at this site. Lesions had been present on average for 2.5 years prior to presentation (range 2-60 months). Lesions were clinically heterogeneous, ranging from macules to crusted shallow ulcers. In 44% of cases, the preoperative clinical diagnosis was that of either squamous cell carcinoma or basal cell carcinoma. The patients thought to have a skin malignancy were 10 years older at presentation, more likely to be male, and more likely to have ulcerative lesions with rapid onset when compared with the other lupus patients. CONCLUSIONS: A subset of patients with lupus (particularly discoid lupus) involving the eyelid have clinical features mimicking patients with squamous epithelial malignancy. In cases such as these, biopsies are critical for establishing the diagnosis and pursuing appropriate therapeutic approaches.

Patterns of GRP78 and MTJ1 expression in primary cutaneous malignant melanoma.

Cell surface expression of glucose-regulated protein 78 (GRP78) occurs in several types of cancer; however, its role in the behavior of primary cutaneous melanoma is not well studied. The association of cell surface GRP78 with other proteins such as MTJ1 stimulates cell proliferation. In this study, we characterized the pattern of expression of GRP78 and MTJ1 in invasive primary cutaneous melanomas and analyzed the relationships between the pattern of expression and various clinicopathological parameters. We found two patterns of GRP78 expression in invasive primary cutaneous melanoma. One pattern showed a gradual fading of protein expression from superficial to deeper levels within the same tumor. The second pattern of expression showed a similar fading with an abrupt regaining of expression at the deep invasive edge of the melanoma. These two distinct patterns of GRP78 expression correlated with both patient survival and depth of tumor invasion. A moderate MTJ1 expression was found to be associated with decreased patient survival; however, no significant associations were observed between patterns of GRP78 and MTJ1 expression. Our study (1) describes two distinct patterns of GRP78 in invasive primary cutaneous melanoma, (2) inversely correlates regain of GRP78 expression with patient survival, and (3) suggests a modifying effect of MTJ1 on GRP78 in enhancing tumor aggressiveness.

Isolated and synchronous vulvar granular cell tumors: a clinicopathologic study of 17 cases in 13 patients.

Granular cell tumors (GCTs) are benign Schwann cell-derived neoplasms occurring throughout the body. Vulvar GCTs are usually isolated, but occasionally multifocal. On account of their anatomic location, surgical interventions aiming for negative resection margins can result in significant morbidity. We describe the clinicopathologic features of 17 vulvar GCTs in 13 patients followed for an average of 7 years. The average age at presentation was 46 years, and 84% of the patients were black. The tumors were multifocal in 3 (23%) patients, and all, either at presentation or subsequently also developed extravulvar foci. Patients with multifocal vulvar GCTs were nearly 10 years younger at presentation than patients in whom the disease was isolated. The most common complaint was a slow-enlarging mass occasionally associated with pruritus or overlying hyperpigmentation. Clinically, the tumors were subcutaneous, mobile, and nodular (2.1 cm on average), without overlying ulceration, and most often were found in the labia majora (6/17). The neoplasms were histologically heterogeneous, but exhibited either a predominantly nodular (3/17) or infiltrative (13/17) pattern of invasion. Cytologically, the tumors displayed round to polygonal cells with a granular cytoplasm, small hyperchromatic nuclei with minimal pleomorphism, and less than 2 mitoses per 10 high power fields. One tumor (1/17) consisted of cells with predominantly vesicular nuclei and prominent nucleoli and was classified as an atypical vulvar GCT. All tumors so examined were reactive for S-100 protein. Eight of 17 tumor excision specimens had positive margins. Of these, 5 tumors remained stable whereas the other 2 with follow-up progressed to require reexcisions after periods of 14 and 8.0 years, respectively. All patients with excisions with negative margins remained stable. Patients with multifocal tumors did not have a higher risk of recurrence per tumor, compared with patients with isolated disease, regardless of the margin status. No patient died from her disease. As granular cell neoplasms have such a low risk or recurrence and behave generally in an indolent manner, aggressive therapy is usually unwarranted.

Paget disease of the vulva: a histologic study of 56 cases correlating pathologic features and disease course.

The Duke experience with 56 vulvar Paget disease patients was analyzed emphasizing pathologic features and controversial issues. Nearly all patients were Caucasian, and their mean age was 69 years. The average length of follow-up was 5.6 years. For each case, the following histologic features were evaluated and their association with disease course was examined: pseudo-invasion, adnexal involvement, signet-ring cells, cytologic atypia, glands formation, epidermal acantholysis, parakeratosis, hyperkeratosis, and chronic inflammation. The recurrence rate after surgical management was 32%, with epidermal acantholysis being the only statistically significant risk factor. Stromal invasion occurred in 10 patients (18%), and was not a statistically significant adverse prognostic indicator, although the single patient who died of the disease had the deepest stromal invasion. Recurrence was more common after resections with positive surgical margins, but this correlation was not statistically significant. Intraoperative frozen section analysis of the margins did not reduce recurrence rate, nor was it useful in attaining permanent free margins. The Paget cells were consistently reactive with cytokeratin-7 and carcinoembryonic antigen and unreactive with S-100 protein, HMB-45, and Mart-1. In addition, the tumor cells were usually positive for mucin stains. This profile helps distinguish vulvar Paget disease from its mimics, Pagetoid squamous cell carcinoma and malignant melanoma.

Acquired vulvar lymphangioma circumscriptum: a comparison of 12 cases with Crohn's associated lesions or radiation therapy induced tumors.

BACKGROUND: Lymphangioma circumscriptum (LC) is a benign lesion of lymphatic origin. Vulvar involvement occurs in various clinical settings. METHODS: We present 12 cases, and compare lesions in patients with Crohn's disease and those associated with pelvic radiation. RESULTS: The average age at presentation was 49 years. Thirty-three percent of the patients had Crohn's disease, 58% had radiation therapy and 9% had no significant medical history. Sixty-seven percent of the patients had multifocal lesions in anatomically distinct regions. Patients presented on average 16 years after onset of predisposing factors. Presenting complaints were pruritus, wetness and vulvar edema. Lesions were clinically heterogeneous, often found on the labia majora. Lesions consisted of dilated lymphatic channels at the junction of the reticular and papillary dermis. The cells lining these spaces lacked cytologic atypicality or mitotic activity. All lesions so examined were immunoreactive for D240. Patients were most often treated with surgical excision followed by laser ablation. Four of twelve patients, all with radiation-associated lesions, experienced disease progression necessitating additional surgery. CONCLUSIONS: Patients with LC secondary to radiation, when compared to those with Crohn's disease, were 10 years younger, more likely to have associated co-morbidities, and frequently experienced disease progression needing additional surgeries. Acquired vulvar LC has multiple causes with differing prognosis.

Pyogenic variant of primary cutaneous anaplastic large-cell lymphoma: a lymphoproliferative disorder with a predilection for the immunocompromized and the young.

Cutaneous anaplastic large-cell lymphoma belongs to the class of primary cutaneous CD30-positive lymphoproliferative disorders. The pyogenic variant is marked by a neutrophil rich inflammatory background. We describe 2 cases (one which clinically presented as cellulitis, and another arising in a patient with Hodgkin lymphoma) and review the clinicopathologic features of cases reported in the literature. In all cases, the male to female ratio is 1.2:1. The average age at presentation for patients with this variant is 47 years old with 15% of patients being 25 years old or younger. Thirteen percent of patients are immunocompromized. Ten percent of patients experience extracutaneous disease progression and 18% of patients are dead at 10 months. Immunophenotypically, the anaplastic large cells demonstrate loss of pan-T cell antigens, CD2, CD3, CD5, and CD7, with 65% of cases expressing CD4 and 29% of cases expressing CD8. Epithelial membrane antigen expression is reported in over half of the cases. In the clinical context of a progressive ulcerating lesion in younger or immunocompromized patients, it is important for the pathologist when presented with a skin specimen demonstrating a neutrophil-rich inflammatory background to include the pyogenic variant of anaplastic large-cell lymphoma. We hope to increase awareness of this rare CD30-positive lymphoproliferative disorder subtype by better defining the clinical spectrum in which this entity can present.