Aleodor A. Andea

Merkel cell carcinoma: correlation of KIT expression with survival and evaluation of KIT gene mutational status

Merkel cell carcinoma is one of the most aggressive primary cutaneous malignancies. Because some Merkel cell carcinomas express the receptor tyrosine kinase KIT, we aimed to evaluate the correlation of KIT expression with the outcome and the presence of activating mutations in the KIT gene in Merkel cell carcinoma. A total of 49 tumors from 40 patients with a diagnosis of Merkel cell carcinoma were identified, of which 30 cases from 21 patients were used in the study. KIT expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded material. Cases were divided into low expressors (0-1+ staining intensity) and high expressors (2-3+ staining intensity). Direct sequencing of exons 9, 11, 13, 17, and 18 of the KIT gene spanning the extracellular, juxtamembrane, and tyrosine kinase domains was performed for cases with high KIT expression. Thirty tumors from 21 patients were analyzed for KIT expression. High KIT expression was seen in 67% of the patients. Five-year survival rates in tumors expressing high versus low levels of KIT were 0% versus 57.8%, respectively; however, this dramatic difference did not reach statistical significance (P = .07). A total of 4 point mutations were identified in 18 tumors analyzed. Two of these were silent mutations involving exons 17 and 18, and 2 involved intron 16-17. Two of the identified mutations may represent novel polymorphisms. Our work suggests a correlation between KIT expression and a worse prognosis in Merkel cell carcinoma patients, raising the possibility of an active role of this receptor in tumor progression and metastasis. However, we did not identify KIT activating mutations in any of the tumors analyzed.

Pigmented extramammary Paget’s disease of the axilla mimicking melanoma: case report and review of the literature

Pigmented Pagets disease is a rare variant that is often confused clinically and histologically with melanoma in situ. Herein, we describe a case of pigmented extramammary Pagets disease involving the axilla of a 79‐year‐old white male thought initially to represent malignant melanoma clinically and histologically. Review of the literature reveals that pigmented variant of Pagets disease, either mammary or extramammary, could be initially misdiagnosed as melanoma unless this entity is considered in the differential diagnosis, and additional confirmatory studies are performed.

Mitotically active proliferative nodule arising in a giant congenital melanocytic nevus: A diagnostic pitfall

Proliferative (cellular) nodules (PN) which mimic malignant melanoma clinically and histologically are described in congenital melanocytic nevi (CMN) and may pose significant diagnostic challenges. We report the case of a 10-day-old male with a giant congenital nevus involving the neck, upper chest, back, and left shoulder containing several nodular lesions, some crusted. Biopsy of a nodule revealed densely packed nevus cells with hyperchromatic round to oval and occasionally irregularly shaped nuclei. There was no necrosis or pushing border, and the nodule blended with the adjacent nevus; however, the lesion demonstrated a significant number of mitoses (27 per mm2) and a 60% labeling index with Ki-67. Further analysis by fluorescence in situ hybridization (FISH) with a 4-color probe set targeting 6p25, 6q23, 11q13, and centromere 6 revealed increased chromosomal copy numbers of all 4 probes, which was interpreted as evidence of polyploidy. In addition, analysis of DNA copy number changes using a single nucleotide polymorphism microarray (Affymetrix, Santa Clara, CA) showed no chromosomal aberrations. The diagnosis of PN in a giant congenital nevus was eventually rendered. At 13-month follow-up, the nodules showed no evidence of growth. Our case illustrates that PNs in the neonatal period might demonstrate extreme mitotic activity. This feature is worrisome when encountered in melanocytic lesions; however, it should not trigger by itself a diagnosis of melanoma in the absence of other histologic criteria of malignancy. In addition, we document polyploidy by FISH in PN, which can potentially be misinterpreted as a FISH-positive result.

Fulminant myocarditis as a late sequela of DRESS: Two cases

Greg P. Bourgeois, MD1, Jennifer A. Cafardi, MD1, Vlada Groysman, MD1, Salpy V. Pamboukian, MD MSPH3, James K. Kirklin, MD4, Aleodor A. Andea, MD2, and Lauren C. Hughey, MD1 1Department of Dermatology, University of Alabama at Birmingham, EFH 414, 1530 3rd Ave S., Birmingham, AL 35294, USA 2Department of Pathology, University of Alabama at Birmingham, PD6A 149, 619 19th St S., Birmingham, AL35294 USA 3Department of Cardiology, University of Alabama at Birmingham, THT 321, 1530 3rd Ave S., Birmingham, AL 35294, USA 4Department of Cardiothoracic Surgery, University of Alabama at Birmingham, THT 760, 1530 3rd Ave S., Birmingham, AL 35294, USA

Keratocystic odontogenic tumor associated with nevoid basal cell carcinoma syndrome: Similar behavior to sporadic type?

Objective: The objective of this study was to analyze the expression of proliferative markers and p53 in keratocystic odontogenic tumor (KCOT) sporadic type and KCOT associated with nevoid basal cell carcinoma syndrome (NBCCS). Study Design and Setting: We performed a cross-sectional study. A total of 19 patients with KCOT were selected from the Oral Pathology Laboratory archives, Central University of Venezuela, from 1995 to 2005. Subjects and Methods: Twelve cases corresponded to sporadic KCOT, and seven cases were associated with NBCCS. Immunohistochemical analysis for p53, proliferating cell nuclear antigen (PCNA), and Ki-67 was performed in all 19 cases. Results: Of the seven cases associated with NBCCS, six (86%) were positive for PCNA. From the 12 sporadic cases, nine (75%) were positive for PCNA. Only one case of sporadic KCOT showed Ki-67 positivity. Five of 12 (42%) cases of sporadic KCOT were positive for p53, and only one (14%) case associated with NBCCS was positive for p53. Conclusion: On the basis of the analysis of the expression of PCNA, Ki-67, and p53, there appears to be no evidence to indicate higher aggressiveness in growth and infiltrative behavior in syndromic KCOT compared with the sporadic type. Therefore, surgical treatment may be approached in the same manner in KCOT sporadic and syndromic with the goal of minimizing recurrence.

Large duct type invasive adenocarcinoma of the pancreas with microcystic and papillary patterns: a potential microscopic mimic of non-invasive ductal neoplasia.

A morphological variant of pancreatic ductal adenocarcinoma forming large ductal elements, large duct type ductal adenocarcinoma, is documented and its clinicopathological features are studied. These tumors may have microcystic and papillary growth patterns that closely mimic the non-invasive cystic and papillary pancreatic tumors such as: intraductal papillary-mucinous neoplasia, including the oncocytic variant, mucinous cystic neoplasms, and ducts involved by pancreatic intraepithelial neoplasia. In a review of 230 pancreatectomy specimens with ductal adenocarcinoma, 28 (8%) cases of large duct type ductal adenocarcinomas were identified according to following criteria: more than 50% of the tumor sections available for examination contained infiltrative ducts with a diameter larger than 0.5 mm or had a macroscopically identifiable microcystic pattern. Overall characteristics of large duct type ductal adenocarcinomas were not too different than those of conventional ductal adenocarcinomas, except that there was a slight female predominance in the former (F/M=2.3). The mean age was 67 (vs 63 in conventional ductal adenocarcinomas; P=0.015), and occurrence in the tail was slightly more common (40% vs 18% in conventional ductal adenocarcinomas; P=0.006). Grossly, cysts measuring up to 1 cm was noted in 10 cases. Microscopically, large duct type adenocarcinomas were characterized by irregularly distributed large ducts with jagged edges, lined by columnar mucinous cells often having deceptively bland cytological features and variable degrees of papillomatosis. Stromal desmoplasia had a hypercellular quality (morphologically distinct from ovarian-like stroma) in four cases, and had a myxoid quality in others. KRAS oncogene mutation was identified in 9 out of 11 cases. Median, 1-year and 2-year survival rates were 16 months, 77% and 30%, respectively, as opposed to 12 months, 52% and 30%, respectively, in conventional ductal adenocarcinoma. In conclusion, it should be recognized that, some (8%) pancreatic ductal adenocarcinomas exhibit a large duct pattern that may microscopically mimic non-invasive pancreatic tumors characterized by cystic and papillary patterns. They may be distinguished by the relatively smaller size of the cysts, irregularity of the duct contours, clustering of the ducts, presence of intraluminal neutrophils and granular debris, degree of cytological pleomorphism, and myxoid quality of the stroma. Clinical behavior appears to be slightly better than that of conventional ductal adenocarcinoma, which may be accounted by the well-differentiated nature of these tumors.

Ultrastructural and molecular confirmation of the trichodysplasia spinulosa-associated polyomavirus in biopsies of patients with trichodysplasia spinulosa.

Trichodysplasia spinulosa (TS) is a rare and only recently characterized cutaneous disease occurring in immunocompromised patients. The disease is characterized by spiny follicular papules on clinical examination and by the presence of viral inclusions at ultrastructural examination. In the last year, this virus has been identified as a new member of the polyomavirus family and designated as TS‐associated polyomavirus (TSPyV). We report two organ transplant patients with this disease in which we were able to identify the TSPyV at ultrastructural and molecular level from formalin‐fixed paraffin‐embedded biopsies of lesional skin. Similar to prior described cases, the patients presented with follicular papules which were concentrated on the central face and associated with alopecia. Histopathology of both cases showed dilated follicular infundibula plugged with cornified eosinophilic cells containing large trichohyaline granules. Transmission electron microscopy on paraffin‐embedded tissue in case 1 showed 28‐nm intracellular viral particles morphologically consistent with polyoma virus. For both cases the presence of TSPyV was confirmed by polymerase chain reaction with virus‐specific primers followed by identification by direct sequencing. These two cases show the presence of the newly described TSPyV in TS further establishing its association with this distinctive disease.

Primary cutaneous peripheral t-cell lymphoma with aberrant coexpression of CD20: Case report and review of the literature

We report an unusual case of primary cutaneous T-cell lymphoma in a 45-year-old male showing expression of the B-cell marker CD20. The lesion presented as a large plaque on the right shin and rapidly developed into additional lesions on the right lower leg and right anterior chest. Despite therapy, bone involvement was discovered at 1 year after initial presentation. Punch biopsy of the right leg revealed a diffuse, atypical dermal lymphocytic infiltrate with papillary edema and no epidermotropism. The atypical cells strongly expressed the T-cell markers CD3, CD2, and CD43, with additional expression of cytotoxic T-cell markers CD8, cytotoxic granule-associated RNA binding protein (TIA-1), and granzyme B and loss of CD7 by immunohistochemistry (IHC). In addition, the atypical cells with the above phenotype exhibited moderate expression of CD20 by IHC. Coexpression of CD8 and CD20 in the atypical cells was confirmed by a dual-labeled IHC stain. Clonal rearrangements of the T-cell receptor γ- and β-chain genes were detected by polymerase chain reaction; however, there was no expression of T-cell receptor β-chain identified by IHC. In conclusion, we present a case a of CD8-positive primary cutaneous T-cell lymphoma with CD20 expression, exhibiting aggressive behavior.

The evolution of histopathologic findings in adult Still disease.

Adult Still disease is an inflammatory arthritis classically associated with daily spiking fevers, evanescent rash, organomegaly, lymphadenopathy, and laboratory anomalies. The typical cutaneous lesions are thin pink papules in a morbilliform distribution, of short duration. Histologically, these lesions are characterized by a superficial perivascular and interstitial mixed dermatitis with lymphocytes and variable neutrophils. A variant clinical presentation is increasingly recognized, which demonstrates persistent hyperpigmented plaques, often with a rippled or linear appearance. The histologic findings consist of upper epidermal dyskeratotic keratinocytes, increased dermal mucin, and a superficial perivascular infiltrate of lymphocytes and possibly neutrophils or eosinophils. We encountered 2 patients who presented with the characteristic rash of adult Still disease, both of whom progressed to develop the pigmented cutaneous plaques. We propose that this variant clinical and histologic appearance is the outcome of persistent disease activity.

Acrokeratosis paraneoplastica (Bazex syndrome): Report of a case associated with small cell lung carcinoma and review of the literature

Acrokeratosis paraneoplastic (Bazex syndrome) is a rare, but distinctive paraneoplastic dermatosis characterized by erythematosquamous lesions located at the acral sites and is most commonly associated with carcinomas of the upper aerodigestive tract. We report a 58-year-old female with a history of a pigmented rash on her extremities, thick keratotic plaques on her hands, and brittle nails. Chest imaging revealed a right upper lobe mass that was proven to be small cell lung carcinoma. While Bazex syndrome has been described in the dermatology literature, it is also important for the radiologist to be aware of this entity and its common presentations.