Workload measurement in subspecialty dermatopathology.

AIM: To measure pathologist workload in subspecialty dermatopathology. METHODS: Three subspecialty dermatopathologists, working in a university-affiliated laboratory, participated in a time-motion study during which they reported 2891 consecutive skin cases received from community-based dermatologists. All pathology reports were retrospectively reviewed and workload measured using the Royal College of Pathologists (RCPath) guidelines and the level 4 equivalent (L4E) method. RESULTS: The majority of dermatopathology cases were scored as low (32%) or intermediate (52%) complexity using the RCPath matrix. Only 16% of cases were considered high or very high complexity. The mean RCPath score per case was 2.68 units. Using L4E complexity levels, 83% of specimens were level 3, 15% were level 4, and only 2% were higher complexity (levels 5 and 6). Mean values for specimens/case, blocks/case, and slides/case were 1.31, 1.52, and 2.92, respectively. Time-motion analysis demonstrated a mean workload per hour of 16.3 cases, 21.3 specimens, 45.1 slides, 43.0 RCPath units, and 12.2 L4E. All three dermatopathologists reported >35 RCPath units per hour. CONCLUSIONS: The RCPath histopathology workload guidelines underestimate the workload achievable by an experienced dermatopathologist, and thus are not directly applicable to subspecialty dermatopathology practice. Hourly work rates 3-4 times that recommended by the RCPath workload matrix are routinely achievable, but extrapolation to yearly workload estimates requires detailed knowledge of practice pattern and time required for non-clinical duties such as teaching, research and administration.

Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations.

BACKGROUND: Germ-line truncating mutations in the E-cadherin (CDH1) gene have been found in families with hereditary diffuse gastric cancer. These families are characterized by a highly penetrant susceptibility to diffuse gastric cancer with an autosomal dominant pattern of inheritance, predominantly in young persons. We describe genetic screening, surgical management, and pathological findings in young persons with truncating mutations in CDH1 from two unrelated families with hereditary diffuse gastric cancer. METHODS: Mutation-specific predictive genetic testing was performed by polymerase-chain-reaction amplification, followed by restriction-enzyme digestion and DNA sequencing in Family 1 and by heteroduplex analysis in Family 2. A total gastrectomy was performed prophylactically in five carriers of mutations who were between 22 and 40 years old. In each case, the entire mucosa of the stomach was extensively sampled for microscopical analysis. RESULTS: Superficial infiltrates of malignant signet-ring cells were identified in the surgical samples from all five persons who underwent gastrectomy. These early diffuse gastric cancers were multifocal in three of the five cases, and in one person infiltrates of malignant signet-ring cells were present in 65 of the 140 tissue blocks analyzed, representing in aggregate less than 2 percent of the gastric mucosa. CONCLUSIONS: We recommend genetic counseling and consideration of prophylactic gastrectomy in young, asymptomatic carriers of germ-line truncating CDH1 mutations who belong to families with highly penetrant hereditary diffuse gastric cancer.

Verrucous carcinoma of the genital tract: is it a distinct entity?

Between 1974 and 1985, 16 patients (7 men, 9 women) with a diagnosis of genital verrucous carcinoma were identified from the cancer registry of the Tom Baker Cancer Centre in Calgary. All the men had lesions on the penis. In the women, five lesions were on the vulva, four were on the cervix and two were on the vagina (two women each had two involved sites). The histologic slides from the surgically excised specimens were reviewed, and, by applying strict criteria, all cases could be reclassified as giant condyloma (five cases), intraepithelial neoplasia with or without condylomatous features (eight cases) or invasive squamous cell carcinoma (five cases). The authors believe that, in genital lesions associated with the human papillomavirus, a diagnosis of verrucous carcinoma is nonspecific and may lead to inappropriate clinical management.

Intestinal metaplasia and dysplasia of prostatic urethra secondary to stricture.

We report a case of intestinal metaplasia and dysplasia (villous adenoma) of the prostatic urethra secondary to stricture of the prostatic portion of the urethra and chronic inflammation. This sequence of events has previously been recognized in the urothelium of the bladder as a precursor of adenocarcinoma of intestinal type. Premalignant dysplasia of glandular type is rare in the urethra, as is adenocarcinoma, and this case suggests that the pathway to some adenocarcinomas of the urethra may be through intestinal metaplasia and dysplasia similar to the process recognized in the stomach, nose, and urinary bladder.

Mesenteric venous thrombosis due to antithrombin III deficiency.

A 19-year-old woman developed gradually worsening abdominal pain, signs of peritonitis, and hematemesis. Laparotomy revealed peritonitis due to segmental small-bowel infarction, and the underlying pathologic condition was mesenteric vein thrombosis. A primary thrombotic disorder was suggested and antithrombin III deficiency was found. Before anticoagulant therapy could be initiated, she developed hemorrhagic cerebral infarction and died. Her history included three episodes of deep vein thrombosis while taking oral contraceptives. Her father died of spontaneous mesenteric and portal vein thrombosis at age 29 years. This report underlines the importance of careful interpretation of the vascular pathology in cases of intestinal ischemia.

PIP: Careful interpretation of the vascular pathology is important in cases of intestinal ischemia caused by primary mesenteric vein thrombosis because it suggests antithrombin III (AT III) deficiency. This deficiency, an autosomal dominant hereditary disorder, predisposes the patient to venous thrombosis. Similar or acquired deficiencies may also predispose the patient to thrombosis. In hereditary AT III deficiency, 90% of the cases have thrombosis of the leg or iliac veins; 8.3% of the cases, thrombosis of the mesenteric veins. Additionally, some families have a tendency to develop mesenteric vein thrombosis specifically. In this case report, a daughter with probable AT III deficiency had a history of 3 episodes of deep vein thrombosis in the previous 5 years while taking oral contraceptives. Her father, with the same deficiency, died from massive intestinal infarction resulting from portal and mesenteric vein thrombosis. The 19-year old woman developed gradually worsening abdominal pain, signs of peritonitis, and hematemesis. A laparotomy revealed peritonitis that was due to segmental small-bowel infarction; the underlying pathologic condition was mesenteric vein thrombosis. Coagulation study results revealed AT III activity by chromogenic assay, 0.48 u/mL; AT III antigen, 0.5 u/mL; and protein C antigen, 1.15 u/mL. 10 days after discharge, she developed a hemicranial headache with nausea, vomiting, neck tenderness, and photophobia; she was readmitted. A CT scan showed a left posterior parietal cerebral infarct. Repeat AT III activity by chromogenic assay was 0.51 u/mL and AT III antigen level was 0.50 u/mL. Before anticoagulant therapy could be initiated, the patient died 7 days after readmission. The combined lowering of AT III activity and antigen levels to half of normal suggests AT III deficiency. Earlier diagnosis of this deficiency could have been made in light of the patient's own history of thrombosis and the paternal history.

Differential immunohistochemical reactions of carcinoid tumors.

Neuron-specific enolase, S-100 protein, and Leu 7 are present in cells showing neuroendocrine differentiation. Leu 7 recognizes myelin-associated glycoprotein, and recent evidence suggests that it further recognizes a subset of neurosecretory granules. Forty-six primary and metastatic carcinoid tumors from various sites were evaluated immunohistochemically with antisera to neuron-specific enolase, S-100, and Leu 7. Only one tumor, a rectal carcinoid, failed to stain with neuron-specific enolase. The remaining cases showed four patterns of staining: nuclear, diffuse cytoplasmic, globular cytoplasmic, or mixed. The pattern of reaction did not correlate with either the embryonic origin or histologic pattern of the tumor. Two patterns of staining were obtained with anti-Leu 7: diffuse cytoplasmic, or dot or ring-like deposition of reaction product. The latter pattern was entirely confined to appendiceal carcinoids. Reactivity with S-100 was in the form of dense positivity in individual cells having a stellate outline. Less intense cytoplasmic positivity and, uncommonly, a mixture of both types of staining were also seen. These histochemical results may lend support to recent evidence suggesting the existence of identifiable subsets of neurosecretory granules in neuroendocrine tumors, including carcinoids.

Fibrous hamartoma of infancy.

Fibrous hamartoma of infancy is an uncommon fibroproliferative lesion that occurs only in infancy and childhood. The present case is unusual for the presence of two separate lesions, infiltration into the superficial muscle, infiltration and entrapment of nerves, and rapid recurrence after initial surgery. Despite these unusual and suspicious features, follow-up evaluations over the 15 months subsequent to the last resection showed no evidence of recurrence.

Metastatic renal carcinoma to larynx.

The larynx is a most unusual site for metastatic cancer. A case of metastatic renal cell carcinoma of the larynx is presented to illustrate the following features: its exceptional indolent course; the difficulty in arriving at a correct diagnosis, and the good result following local excision.

Development of ovarian carcinoma in a cyclosporin A immunosuppressed patient.

This is the first report of an ovarian carcinoma developing in a patient immunosuppressed by Cyclosporin A. Thirteen months before the diagnosis of malignancy, the patient received a living related donor kidney transplant whose rejection was controlled by Cyclosporin A and prednisone. The tumor was rapidly fatal five weeks from diagnosis. The literature on malignant transformation in the immunosuppressed patient is reviewed with emphasis on a gynecologic perspective.