Samih Salama

Interobserver and Intraobserver Variability Using the Fuhrman Grading System for Renal Cell Carcinoma

CONTEXT Histologic grading of renal cell carcinoma has been shown to be second to staging in prognostic significance. A 4-tier grading scheme proposed by Fuhrman et al and based on nuclear features is the system used most frequently in North America. There are, however, very few studies in the literature assessing the interobserver variability for this system, and to our knowledge, none addressing intraobserver variability. OBJECTIVE To assess the interobserver and intraobserver agreement among 4 pathologists using the Fuhrman nuclear grading scheme for renal cell carcinoma. DESIGN Representative hematoxylin-eosin-stained slides of 99 consecutive primary renal cell carcinoma cases diagnosed between 1994 and 1999 at St Josephs Hospital, Hamilton, Ontario, were independently graded by 4 pathologists on 2 occasions with a minimum period of 3 months separating the 2 readings. RESULTS Intraobserver kappa values ranged from 0.29 to 0.62 (mean = 0.45), and interobserver kappa values ranged from 0.19 to 0.38 and from 0.09 to 0.44 for the first and second rounds, respectively (combined mean kappa value = 0.29). When combining Fuhrman grades 1 and 2 as low-grade tumors and grades 3 and 4 as high-grade tumors, the intraobserver kappa values ranged from 0.4 to 0.64 (mean = 0.53) and interobserver kappa values ranged from 0.28 to 0.59 and from 0.26 to 0.58 for the first and second rounds, respectively (combined mean kappa value = 0.45). The admixture of 2 grades in the same tumor was observed in 53% of cases. CONCLUSIONS We found only moderate intraobserver and interobserver agreement using the 4-grade Fuhrman scheme. After collapsing the diagnostic grades to 2, the intraobserver agreement changed from moderate to substantial. The collapsing of the 4-category Fuhrman grades into 2 categories is useful in improving intraobserver agreement.

Sebaceous carcinoma of the face following irradiation

Malignant neoplasms of sebaceous glands are uncommon but generally occur about the head and neck, where these glands are concentrated. The sites of most frequent occurrence are the ocular adnexae, where sebaceous carcinoma presents as an infiltrating malignancy with a poor prognosis. Cutaneous sebaceous carcinoma is rare at other sites but has a better prognosis. We have located eight cases in the literature of sebaceous carcinoma arising in a previously irradiated field: five in the ocular adnexae and three elsewhere on the face. We here report a fourth case of recurrent sebaceous carcinoma with metastases that occurred on the face of an 82-year-old woman who had received radiation to the area for cosmetic epilation 35 years previously.

Malignant melanoma with osteoclast-like giant cells: an unusual host response: immunohistochemical and ultrastructural study of three cases and literature review.

Melanomas with unusual histologic features are very rarely reported in the literature and demonstrate the diversity of melanocytic expression. Three cases of malignant melanoma with osteoclast-like giant cells are reported. Two cases showed undifferentiated malignant cells without melanin pigment and one showed spindled cell morphology. Immunohistochemistry showed that the osteoclast- like giant cells expressed CD68, but not melanocytic markers (HMB45, Melan-A, and S100). Ultrastructural analysis further supports that these cells are reactive histiocytes rather than transformed malignant cells. This suggests they represent an unusual host response, similar to those rarely observed in other neoplasms. Awareness of this entity is important to avoid misdiagnosis of melanoma as a histiocytic tumor. Since only few cases have been reported, greater recognition and documentation may help to evaluate the prognosis of such cases with unusual morphology.

Telepathology for routine light microscopic and frozen section diagnosis.

Telepathology (TP) uses telecommunication linkages to electronically capture, store, retrieve, and transmit images to distant sites. We assessed the feasibility of a dynamic real-time TP system for light microscopic (LM) diagnosis of anatomic pathology specimens, including frozen sections. Six pathologists, in 2 separate periods, read a set of 160 retrospectively retrieved slides (80 of which were frozen sections) by TP and LM. Reading times were recorded. Diagnoses were compared with the reference diagnosis (established by a group of 5 independent pathologists) and graded on a scale of 0 to 2 (2, correct; 1, incorrect but no clinical impact; 0, incorrect with clinical impact). Overall, LM was more accurate than TP compared with the reference diagnosis (score, 1.68 vs 1.54). There was no difference in accuracy between frozen section and paraffin-embedded tissue. Intraobserver agreement ranged from 82.5% to 88.2%. The average reading time was 6.0 minutes for TP and 1.4 minutes for LM. During the study, reading time decreased for TP but not for LM. These results show that despite marginally lower accuracy and longer reading times, TP isfeasible for routine light microscopic diagnosis, including frozen sections.

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.

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

Abstract: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.

Primitive nonneural granular cell tumor (so-called atypical polypoid granular cell tumor). Report of 2 cases with immunohistochemical and ultrastructural correlation.

Primitive nonneural granular cell tumors (so-called atypical cutaneous granular cell tumors) were first described in 1991, followed by few case reports, and 2 recent larger series. We report here 2 additional cases in 2 women aged 73 and 74, who presented with 0.6- and 0.4-cm skin nodules on the right side of the jaw and the forearm, respectively. Biopsies showed cutaneous granular cell neoplasms with epithelioid morphology. The cells exhibited nuclear pleomorphism and brisk mitotic activity with atypical mitoses. Immunohistochemically, the tumor cells expressed vimentin and PGP 9.5 but lacked S-100 and CD34 expression. Ultrastructurally, both cases showed primitive cells packed with large secondary lysosomes. Primitive nonneural granular cell tumors seem to consist of neoplastic proliferating cells that fail to break down uncharacterized cellular material within the lysosomes. They are, however, different from classic granular cell tumor by lacking neural differentiation. Despite reported worrisome cellular atypia, these rare tumors seem to pursue a favorable outcome.

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

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.

Miliarial Gout (A New Entity)

Background: Tophaceous gout typically presents as a subcutaneous, nodular collection of monosodium urate crystals sharply circumscribed from surrounding tissues. Although intradermal cutaneous manifestations of gout have been described, no reported cases of miliarial gout remain. Objective: We describe the first known presentation of miliarial gout and list other uncommon cutaneous manifestations of gouty tophi. The treatment of miliarial gout is discussed, as well as risk factors predisposing an individual to the development of intradermal tophi. Results: Miliarial gout is an intradermal phenomenon consisting of multiple tiny papules containing material of a white to cream color scattered on an erythematous base that responds to allopurinol administration. Risk factors predisposing an individual to the development of intradermal gout include renal insufficiency, hypertension, chronic diuretic therapy, long duration of disease, and lack of consistent use of urate-lowering therapy. Conclusion: Miliarial gout is a unique intradermal manifestation of tophaceous gout.

Sebaceoma of the external ear canal: an unusual location. Case report and review of the literature

Sebaceous neoplasms of the external ear canal are extremely rare. Only two cases of sebaceous neoplasms have been reported in the English literature, a sebaceous carcinoma and a sebaceous adenoma. We report a case of sebaceoma of the external ear canal. To the best of our knowledge, sebaceoma of the auditory canal has not been reported previously. We highlight the differential diagnosis, particularly sebaceous carcinoma and basal cell carcinoma with sebaceous differentiation. Awareness of the possible occurrence of sebaceoma in the auditory canal may prevent the diagnostic pitfall of misidentifying this tumor.