MUC1 and MUC2 in pancreatic neoplasia

MUCs are glycoproteins with various roles in homeostasis and carcinogenesis. Among other actions, MUC1 may inhibit cell-cell and cell-stroma interactions and function as a signal transducer, participating in cancer progression. In contrast, MUC2 is normally found only in goblet cells, where it contributes to the protective barrier function of these cells. Recently, a tumour suppressor role has been demonstrated for MUC2, and both MUC1 and MUC2 appear to have important roles in pancreatic neoplasia. MUC1 appears to be a marker of aggressive phenotype and may facilitate the vascular spread of carcinoma cells. In contrast, MUC2 is rarely detectable in aggressive pancreatic tumours, but is commonly expressed in intraductal papillary mucinous neoplasms (IPMNs), which are rare, indolent tumours, in intestinal IPMNs, and in indolent colloid carcinomas. MUC2 appears to be not only a marker of this indolent pathway, but also partly responsible for its less aggressive nature. Thus, in pancreatic neoplasia, MUC1 and MUC2 have potential diagnostic and prognostic value as markers of aggressive and indolent phenotypes, respectively, and have potential as therapeutic targets.     

Melanoma developing in a nevoid melanocytoma with myxoid changes: a case report

Nevoid and myxoid melanoma are rare variants of melanoma; association of the two is a unique finding. Nevoid melanoma is characterized by morphologic resemblance to a nevus, whereas myxoid melanoma demonstrates a basophilic mucinous matrix. We present an atypical case of a melanoma progressing from a nevoid melanocytoma with myxoid changes. A 78-year-old female presented with a pigmented growth on her right thigh. Biopsy demonstrated a biphenotypic melanocytic proliferation composed of a nodule showing epithelioid melanocytes with enlarged nuclei, prominent nucleoli, lack of maturation, and abundant amphophilic cytoplasm with a rare mitotic figure. These findings were suggestive of melanoma along with a nevoid dermal component and myxoid stroma. FISH testing revealed a homozygous loss of 9p21 in the atypical component. SNP-microarray from the nevoid component demonstrated three abnormalities including a gain of whole chromosome 8, as well as loss of a copy of nearly an entire chromosome 9 and 16q most consistent with a melanocytoma.     

Intraductal and papillary variants of acinar cell carcinomas: a new addition to the challenging differential diagnosis of intraductal neoplasms

The recognition and differential diagnosis of pancreatic intraductal neoplasms (IN) have gained importance in the past few years, as the incidence of these tumors (especially intraductal papillary mucinous neoplasms-IPMNs) have risen to >10% of pancreatic resections, and their significance as precursors of invasive cancer is better appreciated. Acinar cell carcinomas (ACCs) are typically solid tumors; however, we have recently encountered 7 ACCs with either intraductal growth and/or a papillary/papillocystic pattern that could be mistaken for IN. The clinicopathologic features of these cases were studied. Four patients were male and 3 female, with a mean age of 59 and mean tumor size of 4.9 cm (as compared with 10 cm in conventional ACCs). Only 1 patient had metastasis at the time of diagnosis (as opposed to 50% in usual ACCs). In 5 cases, the tumors had nodular growth of sheet-forming acinar cells, some of which were within ducts, as evidenced by the polypoid nature of the process, partial ductal lining, and presence of small tributary ducts in the walls. In 3 cases, the tumor had papillary and/or papillocystic growth, at least focally. All cases had cystic areas. No mucin was identified. All expressed trypsin. Markers of ductal differentiation were either absent or focal. A minor endocrine component was present in 3. The main histologic findings that distinguished these tumors from IPMNs were the more sheetlike nature of the nodules (rather than villous or arborizing papillae), cuboidal cells, overall basophilia of the cytoplasm, prominent nucleoli, apical granules, intraluminal crystals or pale, acidophilic secretions (enzymatic condensations), and lack of mucin. In conclusion, some ACCs show intraductal growth or exhibit papillary patterns, which can mimic IN, especially IPMNs. In such cases, attention to morphologic details described above, and immunohistochemistry are helpful. The clinical significance of this variant is difficult to determine; however, it appears that the tumors are relatively small and metastasis at presentation is less common than typically seen in ACCs (1/7 vs. 50%).     

Evaluation of dual immunohistochemistry and chromogenic in situ hybridization for HER2 on a single section

The evaluation of HER2 status in invasive breast carcinoma can be performed by multiple methods. We assessed the feasibility of performing 2 of these, chromogenic in situ hybridization (CISH) and immunohistochemical staining, on single tissue sections of breast carcinoma. During assay development, sequential performance of immunohistochemical staining after CISH resulted in weaker HER2 expression than that obtained when immunohistochemical staining was performed alone; this was ameliorated by increased antibody incubation time. Performance of both techniques in a combined/hybrid protocol resulted in HER2 protein expression and gene signals identical to those produced by the individual techniques performed alone. Prospective validation of these dual staining protocols in 31 cases of breast carcinoma resulted in 100% concordance with results of CISH when performed alone, but was still associated with a reduced immunohistochemical signal in some cases. Although further testing is needed, we conclude that performance of both immunohistochemical staining and CISH on a single section is possible and could allow for direct "cell-by-cell" comparison of HER2 signals and potentially offer a more economical and real-time method for ongoing validation of HER2 testing.     

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.     

Acute Inpatient Presentation of Kwashiorkor: Not Just a Diagnosis of the Developing World

Abstract: We present the case of an infant with presumed Stevens–Johnson syndrome. Through a history, physical, and histopathology, we were able to diagnose the patient with kwashiorkor. Physicians should be aware of this disorder, which is commonly thought of as a developing world problem, because it is increasing in incidence in industrialized nations because of changing dietary habits.     

Molecular testing for melanocytic tumors: a practical update

The work-up of melanocytic tumors has undergone significant changes in the last years following the exponential growth of molecular assays. For the practicing pathologist it is often difficult to sort through the myriad of different tests available currently for clinical use. The molecular tests used in melanocytic pathology can be broadly divided into 4 categories: (i) Tests useful in the differential diagnosis of nevus versus melanoma (primarily used as an aid in the diagnosis of histologically ambiguous melanocytic tumors), (ii) Tests that predict prognosis in melanoma, (iii) Tests useful in the classification of melanocytic tumors and (iv) Tests that predict response to systemic therapy in melanoma. This review will present an updated overview of major ancillary tests used in clinical practice.     

Lymphedematous fibroepithelial polyps of the penis associated with long-term condom catheter use: case report and review of the literature

Lymphedematous fibroepithelial polyps of the penis are lesions that have only recently been described and are frequently associated with condom catheter use. We report an additional case of lymphedematous fibroepithelial polyps of the penis in association with long-term condom catheter use in a 36-year-old man. Local excision showed large polypoid nodules with compact orthohyperkeratosis and mild acanthosis. The stroma was hypercellular with spindled to stellate fibroblasts and occasional multinucleated cells. Proliferation of small linear to slightly arcuate vessels with some superficial dilatation was a prominent feature. Focal expression of smooth muscle actin and desmin was present in the stroma. Lymphedematous fibroepithelial polyps of the penis are rare lesions with only 11 cases previously reported. We present here an additional example of this entity to highlight the differential diagnosis, the association with condom catheter use and to raise awareness for this unusual diagnosis.