Kong-Bing Tan

Subungual Melanoma: A Study of 124 Cases Highlighting Features of Early Lesions, Potential Pitfalls in Diagnosis, and Guidelines for Histologic Reporting

Subungual melanoma (SUM) is an uncommon variant of melanoma that is often difficult to diagnose, both clinically and pathologically. In an attempt to provide pathologic clues to diagnosis, especially in early lesions or small biopsies, and to provide practical advice to pathologists in reporting, the clinicopathologic features of 124 cases of SUM were reviewed, the largest series reported to date. The features of 28 cases of subungual melanoma in situ (MIS), comprising 4 cases of MIS and 24 cases where areas of MIS were present adjacent to dermal-invasive SUMs, were compared with those of a similar number of acral nevi to identify useful distinguishing features. The median age of the patients was 59 years and the most common site was the great toe (24%). Nine percent of cases were AJCC stage 0, 14% were stage I, 41% were stage II, 32% were stage III, and 4% were stage IV at initial diagnosis. The commonest histogenetic subtype was acral lentiginous (66%), followed by nodular (25%) and desmoplastic (7%). The majority of tumors were locally advanced at presentation with 79% being Clark level IV or V. The median Breslow thickness was 3.2 mm. The median mitotic rate was 3 per mm2 and 33% of cases demonstrated primary tumor ulceration. Seven of 29 patients (24%) who underwent a sentinel lymph node biopsy had nodal disease. Multivariate Cox-regression analysis showed higher disease stage to be the only significant predictor of shortened survival. In comparison to acral nevi, MIS more frequently showed lack of circumscription, a prominent lentiginous growth pattern, predominance of single cells over nests, moderate-to-severe cytologic atypia, a dense and haphazard pagetoid intraepidermal spread of melanocytes, and the presence of junctional/subjunctional lymphocytes (“tumor infiltrating lymphocytes”). Tumor infiltrating lymphocytes have not been highlighted previously as a feature of subungual MIS and represent a useful diagnostic clue. Guidelines for the reporting of SUMs are also presented. Knowledge and recognition of the pathologic features of SUMs and the important features that distinguish them from nevi should reduce the frequency of misdiagnosis.

Keratoacanthoma and Infundibulocystic Squamous Cell Carcinoma

One of the major controversies in dermatopathology is the relationship of keratoacanthoma to squamous cell carcinoma. Leaders in the field remain polarized in their views. Carcinomas with distinct follicular pattern of differentiation have been described in reference to the isthmus as trichilemmal carcinomas, to the follicular bulb as pilomatricomal carcinomas, and to the stem cell or rapidly amplifying cell compartment as basal cell carcinomas (trichoblastic carcinomas). We have employed the term infundibulocystic or infundibular squamous cell carcinoma to identify a subset of squamous cell carcinomas that demonstrate this pattern of differentiation. The recognition of infundibular squamous cell carcinoma is important in that well-differentiated examples are likely to have been diagnosed as keratoacanthoma, whereas moderately or poorly differentiated tumors would be more often reported as squamous cell carcinomas, leading to underrecognition of these infundibular variants of squamous cell carcinoma. The descriptive term infundibulocystic or infundibular squamous cell carcinoma may help to better define an alternative follicular-based pathway to squamous cell carcinoma distinct from the more common evolution from solar keratoses and also refine the classification of keratoacanthoma.

Cyclooxygenase-2 expression: a potential prognostic and predictive marker for high-grade ductal carcinoma in situ of the breast.

Aims : To study cyclooxygenase‐2 (COX‐2) expression in ductal carcinoma in situ (DCIS) of the breast and its association with histological features. COX‐2, an inducible prostaglandin synthase, has been shown to be important in mammary carcinogenesis, being associated with increased tumour size and unfavourable outcome in breast cancer. Animal studies indicate that COX‐2 inhibition is effective in the prevention and treatment of mammary cancers.

Cyclooxygenase 2 expression in nasopharyngeal carcinoma : immunohistochemical findings and potential implications

Background: Cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase, participates in inflammatory and neoplastic processes. It is expressed by various tumours and contributes to carcinogenesis. Notably, COX-2 inhibitors appear to have tumour suppressor effects and are being evaluated in clinical trials. Aims: To investigate COX-2 expression in nasopharyngeal carcinoma (NPC), a common tumour in parts of Asia, and to discuss potential implications. Methods: Eighty five cases of NPC were reviewed. COX-2 immunohistochemistry and semiquantitative assessment of expression in nasopharyngeal biopsies were performed. Because COX-2 is proangiogenic, tumour microvessel density was also assessed with the use of CD31 immunohistochemistry. Results: Histologically, 78 NPCs were undifferentiated, six were non-keratinising, and one was keratinising. Thirty nine NPCs had adjacent dysplastic epithelium. COX-2 expression was noted in 60 NPCs, 14 of 39 samples of dysplastic epithelium, and only one of 25 samples of normal epithelium (p < 0.01). Microvessel density was not significantly different between COX-2 positive and COX-2 negative tumours (p  =  0.774). Tumour COX-2 positivity was not associated with higher tumour stage (p  =  0.423). Conclusion: COX-2 expression is more frequently seen as nasopharyngeal epithelium progresses from normal to dysplastic to carcinoma. This suggests that COX-2 contributes to the multistep process of NPC carcinogenesis. COX-2 represents a therapeutic target for COX-2 inhibitors, and there is thus a basis for the further investigation of this adjuvant treatment modality for NPC. COX-2 inhibitors are known to potentiate the antitumour effects of radiotherapy, which is the primary treatment for NPC.

Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation.

Squamous cell carcinoma (SCC) is a common and important primary cutaneous malignancy. On skin biopsies, SCC is characterized by significant squamous cell atypia, abnormal keratinization, and invasive features. Diagnostic challenges may occasionally arise, especially in the setting of small punch biopsies or superficial shave biopsies, where only part of the lesion may be assessable by the pathologist. Benign mimics of SCC include pseudoepitheliomatous hyperplasia, eccrine squamous syringometaplasia, inverted follicular keratosis, and keratoacanthoma, while malignant mimics of SCC include basal cell carcinoma, melanoma, and metastatic carcinoma. The careful application of time-honored diagnostic criteria, close clinicopathological correlation and a selective request for a further, deeper, or wider biopsy remain the most useful strategies to clinch the correct diagnosis. This review aims to present the key differential diagnoses of SCC, to discuss common diagnostic pitfalls, and to recommend ways to deal with diagnostically challenging cases.

Quality indices in a cervicovaginal cytology service: before and after laboratory accreditation.

CONTEXT Quality assurance practices contribute to the effectiveness of cervical screening and are formalized by participation in a laboratory accreditation program. OBJECTIVE To identify changes in the quality indices of our cervicovaginal cytology service preceding and following laboratory accreditation by the College of American Pathologists in 2000. DESIGN Cervicovaginal cytology quality indices for 2001 (postaccreditation) were compared with those of 1997 (preaccreditation). Performances in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP) for the years 1999-2002 were analyzed. RESULTS A comparison between data for 1997 and 2001 shows the following: (a) a higher inadequacy rate (1.3% vs 0.7%; P <.001) in 2001; (b) maintenance of a low atypical squamous cells of undetermined significance-squamous intraepithelial lesion ratio (0.79 and 0.76, respectively); (c) overall positive predictive values of positive cytology of 82% and 87%, respectively; (d) relatively few changes to the original cytologic diagnoses following review of significant cytohistologic discrepancies (4 cases and 2 cases, respectively); and (e) a higher subsequent positive yield of squamous intraepithelial lesions following atypical squamous cells of undetermined significance diagnoses in 2001 (41% vs 19%; P =.02). The performance of the laboratory and cytotechnologists in the PAP program showed maintenance of a high standard with almost no major discrepancies recorded. CONCLUSIONS An increased awareness of quality-related issues and participation in intradepartmental consultation/diagnostic seminars, all part of the accreditation process, have very likely contributed to the modest improvements identified in the cytology service. Future challenges include increases in workload with the anticipated launch of Singapores national cervical screening program and adaptation to the emerging cervical screening technologies.

Xanthomatous pseudotumor. An unusual postchemotherapy phenomenon in breast cancer.

Neoadjuvant chemotherapy has become an integral part of the treatment for locally advanced breast cancer. It facilitates tumor resectability and also provides an opportunity for the assessment of therapeutic response and prognosis. We report a case in which a large primary breast carcinoma was significantly reduced in size clinically and replaced by a mass lesion that was composed almost entirely of foamy histiocytes. This peculiar phenomenon is described in detail, together with a brief review of the other known postchemotherapy histologic features that include tumor necrosis, tumor cell cytoplasmic vacuolation and marked nuclear atypia, accompanying chronic inflammatory cellular infiltrate, fibrosis, and ductal-lobular atrophy.

Eosinophilic pustular folliculitis.

Classical eosinophilic pustular folliculitis, or Ofujis disease, is a chronic and relapsing dermatosis that is predominantly reported in East Asian populations. Clinically, the disease typically begins as small papules, which enlarge and coalesce into a large plaque, usually on the face. The histopathology is characterized by a prominent eosinophilic infiltrate in the dermis with concentration around pilosebaceous units, often with eosinophilic microabscess formation. The differentiation of eosinophilic pustular folliculitis from other eosinophilic dermatoses is practically challenging and requires close clinicopathologic correlation. Eosinophilic pustular folliculitis may also be associated with human immunodeficiency virus infection, various drugs, and some lymphomas and could also be thought of as a nonspecific dermatopathologic pattern in such settings. The cause of classical eosinophilic pustular folliculitis is unknown, although immune processes are almost certain to play a key role in its pathogenesis.

Extensive hyperpigmented plaques in a chinese singaporean woman: a case of cutaneous plasmacytosis.

Cutaneous plasmacytosis is a rare disease entity presenting with multiple extensive red-brown plaques, histopathology showing marked hyperplasia of mature polyclonal plasma cells, and polyclonal hypergammaglobulinemia on serum protein electrophoresis, in the absence of an underlying secondary cause. We report in this article the first case of cutaneous plasmacytosis from Singapore. A 33-year-old Chinese woman presented with mildly pruritic reddish brown papules and plaques over her trunk and arms for 2 years. Physical examination, laboratory investigations, and radiographic examination were negative for systemic involvement and lymphadenopathy. Serum immunoelectrophoresis showed polyclonal hypergammaglobulinemia with immunoglobulin G and immunoglobulin A. Two sets of skin biopsies performed 2 years apart essentially showed similar histopathological findings of a superficial and deep perivascular infiltrate with numerous mature plasma cells and small typical lymphocytes. There were lymphoid follicles with well-formed germinal centers and mantle zones, surrounded by mature lymphocytes. No light chain restriction was present on immunohistochemistry, and polymerase chain reaction for heavy chain gene rearrangement was negative for monoclonality. Despite potent topical corticosteroids and 8 months of phototherapy with narrow band ultraviolet light, there was no improvement. Intralesional triamcinolone injections to a few lesions afforded temporary relief of itch and flattening of lesions.

Reticular and Myxoid Non-keratinizing Nasopharyngeal Carcinoma: An Unusual Case Mimicking a Salivary Gland Carcinoma

Abstract We present a case of non-keratinizing carcinoma of the nasopharynx (NK-NPC) with an unusual histopathological pattern. The neoplastic cells were arranged in anastomosing cords embedded in a stroma which contained a significant component of alcian blue-positive myxoid substance forming a reticular pattern. These histopathological features gave an initial impression of a salivary gland-type carcinoma. On immunohistochemistry the tumor cells were strongly and diffusely positive for cytokeratins (AE1-3 and 5/6) and p63 and there was strong and diffuse nuclear positivity for Epstein–Barr virus-encoded small RNA on in situ hybridization. This case highlights the histomorphological variability of NK-NPC. Awareness of the histological spectrum of NK-NPC is important in clinical practice and this is not always adequately highlighted in currently used standard textbooks of Head and Neck Pathology.