Assessing Oral Epithelial Dysplasia Risk for Transformation to Cancer: Comparison Between Histologic Grading Systems Versus S100A7 Immunohistochemical Signature-based Grading.

While a 3-tier oral epithelial dysplasia grading system has been utilized for decades, it is widely recognized as a suboptimal risk indicator for transformation to cancer. A 2-tier grading system has been proposed, although not yet validated. In this study, the 3-tier and 2-tier dysplasia grading systems, and an S100A7 immunohistochemical signature-based grading system were compared to assess prediction of risk of transformation to oral cancer. Formalin-fixed, paraffin-embedded biopsy specimens with known clinical outcomes were obtained retrospectively from a cohort of 48 patients. Hematoxylin and eosin-stained slides were used for the 2- and 3-tier dysplasia grading, while S100A7 for biomarker signature-based assessment was based on immunohistochemistry. Inter-observer variability was determined using Cohen's kappa ( K ) statistic with Cox regression disease free survival analysis used to determine if any of the methods were a predictor of transformation to oral squamous cell carcinoma. Both the 2- and 3-tier dysplasia grading systems ranged from slight to substantial inter-observer agreement ( Kw between 0.093 to 0.624), with neither system a good predictor of transformation to cancer (at least P =0.231; ( P >>>0.05). In contrast, the S100A7 immunohistochemical signature-based grading system showed almost perfect inter-observer agreement ( Kw =0.892) and was a good indicator of transformation to cancer ( P =0.047 and 0.030). The inherent grading challenges with oral epithelial dysplasia grading systems and the lack of meaningful prediction of transformation to carcinoma highlights the significant need for a more objective, quantitative, and reproducible risk assessment tool such as the S100A7 immunohistochemical signature-based system.

Evolution of anatomic pathology workload from 2011 to 2019 assessed in a regional hospital laboratory via 574,093 pathology reports.

OBJECTIVE: Quantify changes in workload in relation to the anatomic pathologist workforce. METHODS: In house pathology reports for cytology and surgical specimens from a regional hospital laboratory over a nine- year period (2011-2019) were analyzed, using custom computer code. Report length for the diagnosis+microscopic+synoptic report, number of blocks, billing classification (L86x codes), billings, national workload model (L4E 2018), regional workload model (W2Q), case count, and pathologist workforce in full-time equivalents (FTEs) were quantified. Randomly selected cases (n = 1,100) were audited to assess accuracy. RESULTS: The study period had 574,093 pathology reports that could be analyzed. The coding accuracy was estimated at 95%. From 2011 to 2019: cases/year decreased 6% (66,056 to 61,962), blocks/year increased 20% (236,197 to 283,751), L4E workload units increased 23% (165,276 to 203,894), W2Q workload units increased 21% (149,841 to 181,321), report lines increased 19% (606,862 to 723,175), workforce increased 1% (30.42 to 30.77 FTEs), billings increased 13% ($6,766,927 to $7,677,109). W2Q in relation to L4E underweights work in practices with large specimens by up to a factor of 2x. CONCLUSIONS: Work by L4E for large specimens is underrated by W2Q. Reporting requirements and pathology work-up have increased workload per pathology case. Work overall has increased significantly without a commensurate workforce increase. The significant practice changes in the pathology work environment should prompt local investment in the anatomic pathology workforce.

Immunohistochemistry Use by Diagnostic Category and Pathologist in 4477 Prostate Core Biopsy Sets Assessed at Two Hospitals.

BACKGROUND: Immunohistochemistry (IHC) use in prostate cores is not routinely determined and its value assessed. METHODS: Pathology reports for cases accessioned 2011 to 2017 at two hospitals were retrieved. IHC orders by pathologist and hospital were extracted with a custom program and tabulated. The diagnostic category (and highest grade cancer if applicable) was obtained by a hierarchical (free text) string matching algorithm. RESULTS: The study period contained 4477 biopsy sets. Categorized by worst pathology (% stained), the cohort was: benign: 1184 cases (42%); prostatic intraepithelial neoplasia: 168 (68%); suspicious: 323 (93%); grade group 1 cancer (WHO1): 900 (78%); grade group two (WHO2): 840 (60%); WHO3 cancer: 451 (54%); WHO4 cancer: 363 (46%); WHO5 cancer: 215 (56%); cancer grade not specified: 33 (52%). The hospital was a predictor; site A(2716 biopsies) and site B(1761) accounted for 10,183 and 14,852 IHC, respectively. The cases with IHC decreased in the last 4 years (site A: 57->45%, site B: 79->73%). Thirty-five pathologists read >20 cases each and together interpreted 4418 (range, 21 to 415; median, 88). In total 24,766 IHCs were done on the 4,418 cases (5.6/case). The mean/median/SD/max/min IHCs/case for the 35 pathologists was 5.6/4.1/3.9/15.2/0.9. High IHC users (1st and 2nd quintile pathologists) called more suspicious for malignancy but not significantly more WHO1 than low IHC users. CONCLUSIONS: IHC use is most frequent at the benign/malignant interface, and dependent on the pathologist and hospital; however, it is independent of WHO1 cancer rate. Diagnostic rate information can inform and define appropriate and rational IHC use. We plan to follow IHC utilization retrospectively in relation to the diagnostic category going forward.

A Challenging Case of Mammary Analogue Secretory Carcinoma: Case Study with Ultrastructural and Cytogenetic Correlation.

Mammary analogue secretory carcinoma (MASC) is a rare salivary gland tumor analogous to secretory carcinoma of the breast. The diagnosis of MASC can be challenging due to substantial morphologic and immunohistochemical similarities with other salivary gland tumors. The differential diagnosis of MASC is broad and includes intraductal carcinoma, acinic cell carcinoma, and adenocarcinoma, not otherwise specified. Although molecular testing for ETV6 gene rearrangement is characteristic of MASC and has not been shown in any other salivary gland tumor, a particular challenge arises when such testing is unavailable, or when molecular testing for ETV6 gene rearrangement is negative in a suspected case of MASC. Our study presents the diagnostic workup of a challenging case of MASC with immunohistochemistry, electron microscopy, and cytogenetic studies performed to resolve the diagnosis.

Next Generation Quality: Assessing the Physician in Clinical History Completeness and Diagnostic Interpretations Using Funnel Plots and Normalized Deviations Plots in 3,854 Prostate Biopsies.

BACKGROUND: Observational data and funnel plots are routinely used outside of pathology to understand trends and improve performance. OBJECTIVE: Extract diagnostic rate (DR) information from free text surgical pathology reports with synoptic elements and assess whether inter-rater variation and clinical history completeness information useful for continuous quality improvement (CQI) can be obtained. METHODS: All in-house prostate biopsies in a 6-year period at two large teaching hospitals were extracted and then diagnostically categorized using string matching, fuzzy string matching, and hierarchical pruning. DRs were then stratified by the submitting physicians and pathologists. Funnel plots were created to assess for diagnostic bias. RESULTS: 3,854 prostate biopsies were found and all could be diagnostically classified. Two audits involving the review of 700 reports and a comparison of the synoptic elements with the free text interpretations suggest a categorization error rate of <1%. Twenty-seven pathologists each read >40 cases and together assessed 3,690 biopsies. There was considerable inter-rater variability and a trend toward more World Health Organization/International Society of Urologic Pathology Grade 1 cancers in older pathologists. Normalized deviations plots, constructed using the median DR, and standard error can elucidate associated over- and under-calls for an individual pathologist in relation to their practice group. Clinical history completeness by submitting medical doctor varied significantly (100% to 22%). CONCLUSION: Free text data analyses have some limitations; however, they could be used for data-driven CQI in anatomical pathology, and could lead to the next generation in quality of care.

Endocrine Mucin-Producing Sweat Gland Carcinoma, a Histological Challenge.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare adnexal tumor of the skin with low-grade cytological features and neuroendocrine differentiation. It has a predilection for the skin of the eyelid, but has also been reported in the face and rarely extra-facial locations. The tumor is seen more frequently in women and on average affects the elderly. It is histologically and immunohistochemically analogous to solid papillary carcinoma of the breast/endocrine ductal carcinoma in situ with a nodular, solid, papillary, and/or cribriforming architecture, neuroendocrine differentiation, and mucin production. Since it was first described by Flieder et al. in 1997, less than 60 cases have been reported in literature. We describe the morphological and immunohistochemical features of another case with a review of the common histological differential diagnoses and emphasize the salient features that help distinguish this rare neoplasm.

High-Resolution Magnetic Resonance Imaging of Scalp Arteries for the Diagnosis of Giant Cell Arteritis: Results of a Prospective Cohort Study.

OBJECTIVE: To examine the concordance between high-resolution magnetic resonance imaging (MRI) of the scalp arteries and temporal artery biopsy for the diagnosis of giant cell arteritis (GCA). METHODS: We conducted a prospective cohort study of patients with suspected GCA. Participants underwent high-field 3T MRI of the scalp arteries followed by temporal artery biopsy. Arterial wall thickness and enhancement on multiplanar postcontrast T1-weighted spin-echo images were graded according to a published severity scale (range 0-3). MRI findings were compared with temporal artery biopsy results and the American College of Rheumatology (ACR) criteria for GCA. RESULTS: One hundred seventy-one patients were included in the study. Temporal artery biopsy findings were positive in 31 patients (18.1%), and MRI findings were abnormal in 60 patients (35.1%). ACR criteria were met in 137 patients (80.1%). With temporal artery biopsy as the reference test, MRI had a sensitivity of 93.6% (95% confidence interval [95% CI] 78.6-99.2) and a specificity of 77.9% (95% CI 70.1-84.4). The corresponding negative predictive value of MRI was 98.2% (95% CI 93.6-99.8) and positive predictive value was 48.3% (95% CI 35.2-61.6). CONCLUSION: In patients with suspected GCA, normal findings on scalp artery MRI are very strongly associated with negative temporal artery biopsy findings. This suggests that MRI could be used as the initial diagnostic procedure in GCA, with temporal artery biopsy being reserved for patients with abnormal MRI findings.

A Case of Patch Stage of Kaposi's Sarcoma and Discussion of the Differential Diagnosis.

A 55 year old HIV positive male had a skin lesion biopsy which showed atypical vascular proliferation within the superficial and deep dermis with mild atypia of lining endothelial cells. A sparse lymphoplasmacytic infiltrate surrounding the irregular vascular channels was noted. Immunohistochemistry highlighted the atypical blood vessels with the vascular markers CD31, CD34 and Factor VIII. The differential diagnosis included unusual vascular or lymphatic proliferations, stasis dermatitis, kaposiform hemangioendothelioma, progressive lymphangioma and angiosarcoma with focal Kaposi's sarcoma features. Characteristic human herpes virus-8 positive staining helped support the diagnosis of patch stage of Kaposi's sarcoma. Herein, we discuss the case findings, differential diagnosis and characteristic histological findings associated with the patch stage of Kaposi's sarcoma which can be an elusive diagnosis.

Amelanotic Melanoma Presenting with Plasmacytoid Morphology and BRAF V600 Mutation.

Plasmacytoid melanoma is an unusual variant of malignant melanoma. The plasmacytoid morphology can be found in a variety of other malignancies including carcinomas, plasma cell neoplasms, lymphoproliferative disorders, and sarcomas. The authors report a rare case of plasmacytoid amelanotic malignant melanoma in a 78-year-old man presenting with an enlarging palpable, erythematous mass on his left posterior shoulder. A fine needle aspirate showed atypical findings with single amelanotic cells with high nuclear to cytoplasmic ratio, mono- and multi-nucleation with prominent nucleoli and intranuclear inclusions. Review of the excision and immunohistochemical analysis revealed the malignant plasmacytoid cells stained with vimentin, S-100, HMB-45, and other staining patterns consistent with melanoma. Initial evaluation was negative for other sites of disease. However, 4 months later, the patient was noted to have metastatic disease to his lungs and liver. Given that the tumor was noted to be BRAF V600R mutated, the patient was started on single agent dabrafenib. The plasmacytoid morphology can be found in a variety of malignancies. Melanoma should be considered in the differential diagnosis of any malignancy presenting with plasmacytoid features.

Cutaneous collagenous vasculopathy: a new case series with clinicopathologic and ultrastructural correlation, literature review, and insight into the pathogenesis.

Cutaneous collagenous vasculopathy (CCV) is a rare distinct idiopathic microangiopathy of the superficial cutaneous vasculature. Seven new cases are reported (6 females and 1 male) ranging in age from 42 to 85 years, with some showing unusual clinical and histopathological findings. All presented with macular telangiectases starting on the lower extremities and spreading progressively in 5 cases and were suspected to have generalized essential telangiectasia. Two cases had a history of over 20 years. One case had lesions in the abdominal striae, and 1 was markedly ecchymotic. All skin biopsies showed the characteristic features of CCV with dilatation and marked thickening of the walls of superficial dermal blood vessels displaying reduplication of the basement membrane on periodic acid-Schiff-diastase stain and deposition of hyaline collagenous material immunostaining as collagen type IV, and showing decreased or absent actin staining. However, the changes were subtle and only seen focally in some biopsies. Few lymphoid cells were present around occasional vessels. Electron microscopy showed increased basement membrane lamellae with marked deposition of normal and some abnormal collagen (Luse-like bodies) and focal endothelial damage, suggesting reparative perivascular fibrosis resulting from repeated endothelial injury. These cases (and all 18 previously reported ones) are of a wide age range and no gender predilection. This disorder is underdiagnosed, and it is likely that some cases clinically suspected to be generalized essential telangiectasia may actually represent CCV. Better recognition by dermatologists may lead to more biopsies from patients with generalized telangiectasia and a further understanding of the pathogenesis of CCV and its relationship to other cutaneous vascular disorders.

Primary cutaneous versus salivary gland origin mucoepidermoid carcinoma.

Mucoepidermoid carcinoma (MEC) is a malignant glandular epithelial neoplasm that most commonly arises in the major salivary glands. Primary cutaneous MEC is very rare. There is a particular diagnostic challenge in determining the primary site of MEC when it is found in skin overlying the parotid gland. Attention to a combination of morphologic findings may be helpful. However, differentiation of primary cutaneous MEC from secondary cutaneous involvement by a parotid MEC may be unnecessary once the parotid gland is infiltrated. We report the case of a 54-year-old male with a 2-cm asymptomatic mass overlying the right parotid gland, which was managed by excision of the affected skin, right total parotidectomy, and right neck dissection. Histopathologic and immunohistochemical findings were consistent with a cutaneous intermediate-grade MEC. Postoperative radiotherapy was deferred. The patient showed no evidence of recurrence or metastasis at 2 months before self-discontinuing follow-up. To our knowledge, this is only the second reported case of MEC involving the parotid gland, but of overlying primary cutaneous origin.

Cutaneous lymphadenoma: a rare case and brief review of a diagnostic pitfall.

We report a case of cutaneous lymphadenoma on the posterior left ear of a 67-year-old woman. Although it is benign, recognition of cutaneous lymphadenoma is important as it presents a diagnostic pitfall to the unsuspecting dermatologist and general surgical pathologist, who may readily misdiagnose the lesion because it is not only very rare, but also clinically and histologically resembles the far more common and locally destructive basal cell carcinoma.

Cutaneous collagenous vasculopathy associated with intravascular occlusive fibrin thrombi.

Cutaneous collagenous vasculopathy (CCV) is a rare cutaneous microangiopathy that clinically resembles generalized essential telangiectasia with only 12 cases reported to date. The perivascular fibrosis is thought to be due to production of abnormal collagen by veil cells in the outer vessel walls as a result of unknown factors. This report is of an 84-year-old male with progressive telangiectasia. Biopsies showed characteristic features of CCV. In addition, there were multiple intravascular fibrin thrombi, some organizing and associated with endothelial cell hyperplasia with recanalization reminiscent of glomeruloid bodies and simulating reactive angioendotheliomatosis (RAE). Histochemically and ultrastructurally fibrin was noted within the vessel walls integrating into the fibrous tissue around the vessels; however, the patient had no evidence of coagulation disorder, cryoglobulinemia or cold agglutinemia. Immunofluorescence showed fibrinogen within the vessel walls but no immunoglobulins or C3. As well, there were minimal inflammatory cells. This suggests pauci-inflammatory injury to the endothelial cells by unknown angiogenic factors causing local intravascular fibrin thrombi with fibrin leaking and incorporating into the vessel walls, eventually leading to reparative perivascular fibrosis. This case suggests that some cases of CCV are related to a primary local intravascular occlusive thrombotic microangiopathy. However, the primary triggering factor causing the endothelial cell damage has yet to be elucidated.

Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical pathology sign out.

Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare and poorly differentiated variant of squamous cell carcinoma. The lesion is histologically identical to undifferentiated nasopharyngeal carcinoma (lymphoepithelioma), but with Epstein-Barr virus involvement documented rarely. The first case of LELCS was described in 1988 by Swanson et al. and since there has been less than a total of 60 cases documented. This case review discusses a 87 year old man who presented to his primary care physician with a 2.5 cm solitary ulcerated nodular lesion on his right chest for two weeks. The patient ultimately had the lesion excised and sent for histological examination. The microscopic examination, ancillary studies used and differential diagnosis considered are discussed in detail in the following report. This case review aims to provide insight and approach to a rare cutaneous neoplasm, with the conclusions supporting a theory that LELCS is a separate entity from lymphoepithelioma.

Radiology-pathology conference: neutrophilic fasciitis and panniculitis of the feet (Sweet's syndrome).

Sweet's syndrome is characterised by pyrexia, cutaneous lesions, neutrophilia and an infiltrate of mature neutrophils in the dermis. While extracutaneous disease is not uncommon, neutrophilic fasciitis has rarely been described. We report the imaging appearances with clinical and histological correlation of a case of drug-induced neutrophilic fasciitis in a 56-year-old man.

CD99 expression in Merkel cell carcinoma: a case series with an unusual paranuclear dot-like staining pattern.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine cancer of the skin. The utility of CD99 (MIC-2) in the diagnosis of MCC has been previously studied, with reported rates of expression ranging from 13 to 55%. When specified, a membranous or cytoplasmic staining pattern was considered significant. Recent studies of CD99 have identified a paranuclear dot-like expression pattern in certain non-neuroendocrine pancreatic and colonic lesions. We recently noted paranuclear dot-like staining in several cases of MCC, including cases lacking cytokeratin 20 (CK20) expression. METHODS: Fourteen cases of MCC were stained with CK20 and CD99 antibody, and the pattern and intensity of staining were recorded. Seven cases of pulmonary small cell carcinoma (PSCC) and one case of primitive neuroectodermal tumor (PNET) were used for comparison. RESULTS: All 14 cases of MCC showed at least focal CD99 staining, with both membranous and paranuclear dot-like staining patterns identified. CK20 staining was present in 12/14 cases, with the characteristic dot-like pattern identified. Four of seven cases of PSCC showed CD99 staining, with two showing a finely granular dot-like staining pattern. CONCLUSIONS: We report an unusual pattern of paranuclear dot-like expression of CD99 in 14 cases of MCC, two of which did not express CK20. This previously unrecognized expression pattern may be of use in differentiating MCC from other cutaneous malignancies, especially when CK20 expression is limited or absent.

Cutaneous presentation of post-renal transplant lymphoproliferative disorder: a series of four cases.

We report detailed histological and molecular characteristics of four post transplant lymphoproliferative disorders (PTLD) presenting in the skin of renal transplant patients, and their clinical outcome. Three had B-cell lymphomas (cases 1-3), and one had a T-cell lymphoma (case 4). All B-cell lymphomas showed Epstein-Barr virus (EBV) by immunohistochemistry (IHC) or in situ hybridization (ISH). Cases 1 and 2 were large cell lymphomas, and case 3 a plasmacytoma. Case 1 showed light chain restriction and heavy chain gene rearrangement by polymerase chain reaction (PCR). The patient was then diagnosed with an abdominal lymphoma and died of sepsis. Case 2 had no recoverable DNA. Case 3 had a plasmacytoma that showed monoclonal light chain restriction on IHC and an oligoclonal heavy chain rearrangement by PCR. In cases 2 and 3, the lesions regressed following reduction of immunosuppression, and died 1.5 and 8 years later from unrelated medical causes. Case 4 was a CD 30+ anaplastic large T-cell lymphoma with no EBV detected by IHC, ISH and PCR, and died of heart failure 2 years later. Cutaneous manifestations of PTLD are rare, show wide array of clinical and pathological features, and generally have a favorable prognosis. EBV appears to be associated only with B-cell cutaneous lymphomas.