Observational Study Examining the Diagnostic Practice of Ki67 Staining for Melanocytic Lesions.

BACKGROUND: Dermatopathologists routinely use Ki67 immunostaining to assess atypical melanocytic lesions with a dermal component to determine whether an ambiguous tumor is melanoma. However, there is no universal standard of use for Ki67 in melanocytic neoplasms. We sought to observe the real-world use of Ki67 in the diagnosis of melanocytic lesions and establish a best practice recommendation. METHODS: We searched dermatopathology reports from 2 academic practices for melanocytic lesions in which Ki67 staining was used for diagnosis. The proliferation rate was compared between cases diagnosed as benign (not requiring re-excision), moderate to severely dysplastic or atypical Spitz nevi (requiring re-excision), and malignant melanoma. The use of other melanocytic markers and consensus review was also recorded and compared between institutions. RESULTS: Pathology reports for 106 cases were reviewed. A high Ki67 proliferation rate (n = 18) favored a diagnosis of melanoma or nevi requiring re-excision (15/18, 83.3%) versus a benign nevus (3/18, 16.67%). A high Ki67 rate was 71.4%-90.9% sensitive and 40%-56% specific for the diagnosis of nevus requiring re-excision or melanoma. Institutional practices differed in regard to reporting of Ki67 staining, the use of multiple markers in the workup of atypical melanocytic lesions (HMB45, Melan-A, Ki67 being most common), and consensus review. CONCLUSIONS: A negative or low Ki67 proliferation rate correlates well with rendering of a benign diagnosis. However, a low proliferation rate does not preclude the diagnosis of melanoma. Ki67 staining is most commonly used as an ancillary test to support a diagnosis after other factors have been considered, such as histopathologic morphology and results of additional concurrently used stains.

Distinguishing pustular psoriasis and acute generalized exanthematous pustulosis on the basis of plasmacytoid dendritic cells and MxA protein.

BACKGROUND: Distinguishing acute generalized exanthematous pustulosis (AGEP) and pustular psoriasis (PS) can be challenging. Staining for plasmacytoid dendritic cells, or PDCs (producer of IFN-α/ß), and MxA (an IFN-α/ß inducible protein) may help discriminate these entities. METHODS: Forty-three cases of AGEP and PS were compiled from two academic institutions. All cases were examined for CD123+ PDCs, eosinophils, acanthosis, papillomatosis, suprapapillary plate thinning, tortuous dilated capillaries, single necrotic keratinocytes, papillary dermal edema, vasculitis, eosinophil exocytosis, intraepidermal pustules, and subcorneal pustules. A subset of cases (n = 26) was stained for MxA. RESULTS: Perivascular and intraepidermal PDCs, dilated tortuous vessels, and MxA expression in the dermal inflammatory infiltrate were significantly (P < 0.05) in favor of a diagnosis of PS. The absence of PDCs and presence of eosinophils favored a diagnosis of AGEP (P < 0.05). CONCLUSIONS: We found compelling evidence for the use of CD123 to highlight PDCs in these cases. The presence of PDCs and expression of MxA in dermal inflammatory infiltrate, as well as absence of eosinophils and presence of tortuous dilated capillaries favored a diagnosis of PS. Expression of MxA in the dermal infiltrate corresponds with a Th1 pathway in PS and may indicate a Th1 component in the early initial phase of AGEP.

Cutaneous/subcutaneous mesenchymal proliferations of the breast.

Cutaneous mesenchymal "spindle cell" lesions arising in the vicinity of the breast represent a complex clinical and diagnostic scenario which may overlap histopathologically and immunohistochemically with mammary spindle cell proliferations, potentially impacting management and overall prognostication. In this review, we suggest a pattern-based approach to assist in the evaluation of these lesions. A comprehensive description of each entity is accompanied by a cutaneous and mammary differential diagnosis.

Giant benign intradermal melanocytic nevus of rapid onset.

Benign melanocytic nevi are slowly growing acquiredor congenital tumors with varied morphology,commonly encountered in dermatology clinics. Anytumor with rapid clinical growth must be assessedcarefully in order to exclude malignancy. We report awoman with a histopathologically benign intradermalnevus that presented as a rapidly evolving largecutaneous mass on the ear. Owing to the discrepancybetween the clinical and histopathological findings,an extensive histopathological work-up involvingmany deeper sections, immunohistochemical stains,and fluorescent in situ hybridization (FISH) analysiswas conducted in order to rule out malignancy.

Neighboring look-a-likes: distinguishing between breast and dermatologic lesions.

Due to the proximity of the skin, subcutis, and axilla to the breast, the possibility of a "breast mass" actually representing a dermatologic lesion should be considered, particularly if the proliferation does not look characteristically "mammary" in appearance. Even more underappreciated is the scenario of a dermatologic proliferation morphologically masquerading as a breast tumor. The pathologist can fall prey to this pitfall if he/she is led to believe that the location of the tumor is the breast proper. The aim of this review is to provide an overview of dermatologic mimickers of breast lesions and helpful ways to discern between them when possible.

Agminated syringocystadenoma papilliferum: a new clinical presentation of a rare benign adnexal neoplasm.

Syringocystadenoma papilliferum is a rare adnexal tumor that often occurs as a solitary tumor in the head and neck region, although occurrences on other anatomical locations have been described. Linear configurations have been described, but an agminated form is a more rare and underreported variant of this tumor. We describe a case of a healthy 10-year old female with agminated syringocystadenoma papilliferum occurring on her left supraclavicular region, with the clinical appearance of grouped molluscum contagiosum papules.Case synopsis A healthy 10-year-old girl was referred for the treatment of a "collection of molluscum contagiosum" of the left supra clavicular region of several years duration. The lesions were asymptomatic and refractory to cryotherapy. The patient was a healthy girl with no significant systemic findings. Cutaneous exam revealed a clustered group of pink, dome shaped, umbilicated papules over a 1.5 x 1 cm area within the left supraclavicular fossa (Figure 1a). An excisional biopsy was performed. Routine H&E stained sections revealed cystic epidermal invaginations with papillary projections. The superficial portions of the cyst were lined by stratified keratinizing epithelium, whereas the deeper papillated portion exhibited a double layer of basal-like cells and luminal eosinophilic columnar cells with focal decapitation secretion. The papillary structures contained fibrovascular cores and lymphoplasmacytic infiltrates. A component of hamartomatous follicular growth was not identified (Figure 1b-d.). A diagnosis was made of agminated syringocystadenoma papilliferum.

Renal transplant patient with polyoma virus bladder infection and subsequent polyoma virus nephropathy.

Polyoma virus nephropathy (PVN) is a significant cause of renal allograft dysfunction in transplant patients. A 58-year-old male received a cadaveric renal transplant and 12 weeks later presented with fever, diarrhea, and dysuria. He was diagnosed with a polyoma virus infection of the bladder by a transurethral bladder biopsy. One year post-transplant, he presented with renal allograft dysfunction and was diagnosed by biopsy with PVN of the non-native kidney. The diagnosis of a polyoma virus infection was confirmed by immunoreactivity to the polyoma T-antigen. We suggest that polyoma virus infection of the bladder be included in the differential diagnosis of urinary dysfunction in post-transplant patients, as such infections might be an under-recognized comorbidity in individuals with PVN.

Expression of p53 in virally infected tubular cells in renal transplant patients with polyomavirus nephropathy.

Polyomavirus (PV) infection is associated with ureteral stenosis, hemorrhagic cystitis, and interstitial nephritis in renal transplant patients. The 3 PVs detected in human beings-BK virus, JC virus, and simian virus 40-each encode highly homologous forms of a large T antigen, a transcriptional and replicational regulatory protein. We describe immunohistochemical findings in 5 renal transplant patients who developed PV nephropathy (PVN) and a sixth patient with both PVN and PV infection of the bladder mucosa. Polyomavirus infection was confirmed by immunohistochemical detection of T antigen in kidney and bladder biopsies. We report on the expression of p53 specific to virally infected cells in all biopsies positive for T antigen. Examination of posttransplant biopsies obtained from these 6 patients before they were diagnosed with PVN revealed no expression of T antigen or p53. Accumulation of p53 in PV-infected cells may occur in response to binding of p53 by T antigen, resulting in stabilization of p53. These results provide the first evidence for intracellular actions of PV T antigen in the context of nonneoplastic diseases.

Polyoma virus infection is a prominent risk factor for bladder carcinoma in immunocompetent individuals.

Despite various reports of BK viral (BKV) DNA sequences or proteins in tumors of the urogenital tract, there has been no study statistically linking infection by this polyoma virus (PV) to tumor development. All PV are potential transforming viruses, the large T-antigen of which interacts with tumor suppressor proteins. Here, we have performed a cross-sectional study of 3,782 patients having had urine cytologic analyses, comparing those diagnosed with PV infection with those not so diagnosed. In order to focus on immunocompetent individuals, renal transplant patients, for whom a diagnosis of PV infection followed immunosuppressive therapy, were excluded. Among the 133 immunocompetent patients diagnosed with PV infection, the most frequently occurring neoplasms were bladder carcinoma (15.8%) and prostate carcinoma (3.8%). The incidence of bladder carcinoma was sufficient to statistically establish temporality in a two-sided test, linking a prior diagnosis of PV infection to a subsequent diagnosis of bladder carcinoma (odds ratio = 3.419, P < 0.001).