Quantitative assessment of dermal cellularity in nephrogenic systemic fibrosis: a diagnostic aid.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) affects patients with impaired renal function who have received gadolinium-containing contrast agents (GCCAs). Increased dermal cellularity is a key diagnostic feature of NSF, however, the histologic findings can be subtle. OBJECTIVE: We sought to determine whether dermal cellularity in skin biopsy specimens from NSF cases: (1) differs significantly from that of controls; and (2) correlates with duration of the skin lesions, level of plasma creatinine, GCCA dose, or a combination of these. METHODS: Seventeen NSF skin biopsy specimens and age-, sex-, and site-matched controls were retrieved from the dermatopathology files of the Massachusetts General Hospital in Boston. Dermal cellularity was manually quantified on hematoxylin-eosin-stained sections and patient medical records were reviewed for demographic and clinical data. RESULTS: NSF cases showed a mean dermal cellularity of 70.8/high-power field (control mean: 14.4/high-power field, P < .001) and a cut-off range of 19 to 26/high-power field was established. No significant correlation was identified between dermal cellularity and demographic and clinical data. LIMITATIONS: In this retrospective analysis, duration of skin lesion was defined as the interval from most recent prior GCCA study, rather than the actual clinical onset, to time of skin biopsy, and the cumulative GCCA dose may reflect a minimum if GCCA was received at an outside institution. CONCLUSION: Enumeration of dermal cellularity on hematoxylin-eosin-stained sections can aid in the histologic diagnosis of NSF in the setting of chronic kidney disease and GCCA exposure and is independent of patient age, sex, plasma creatinine, time from last GCCA exposure, and GCCA dose.

Erythema dyschromicum perstans.

A 39-year-old Hispanic man presented with widespread, symmetric, hyperpigmented, brown-gray-blue, oval-to-circular, discrete and coalescing patches on the upper extremities, trunk, neck and face, many with an associated annular erythematous border. Histopathologic features showed an interface dermatitis, thin lichenoid and superficial perivascular infiltrates, and dermal melanophages. These changes were consistent with a diagnosis of erythema dyschromicum perstans (EDP). The etiology of EDP is unknown, but many associations have been described. The rim of erythema that appears during the inflammatory phase of the disorder distinguishes it from other disorders of hyperpigmentation. There is no consistently effective treatment for EDP. We highlight the use of narrow-band UV B phototherapy in the treatment of this disorder, which has shown good success in our patient thus far.

Infiltrating intramuscular spindle cell lipoma of the face.

Spindle cell lipoma is a benign lipomatous tumor, which usually arises on the back of the neck, shoulder or upper back of males in the third to seventh decade of life. We report herein an unusual infiltrating intramuscular spindle cell lipoma arising in the nose of a 53-year-old man. The patient presented with a 0.5-cm 'cyst' of the nose, just above the right alar crease, which was removed. Four years later, the lesion recurred and was re-excised. Histologically, a proliferation of mature adipocytes, ropey collagen fibers and spindle cells within a myxoid stroma was present in the subcutaneous tissue and infiltrated between skeletal muscle fibers. Nine cases of intramuscular spindle cell lipoma with histological examination have previously been reported and have involved the oral cavity and muscles of the extremities. To our knowledge, this is the first report of an infiltrating intramuscular spindle cell lipoma arising on the face.

Collagenous vasculopathy: a report of three cases.

Cutaneous collagenous vasculopathy (CCV) is an idiopathic microangiopathy involving the superficial blood vessels that was initially reported in a 54-year-old male. We recently have identified this rarely reported entity in three Caucasian males. The first patient was a 59-year-old male with diabetes, hypertension and hypercholesterolemia who presented with multiple, red, blanchable, asymptomatic telangiectasias covering the extensor surface of the forearms, the lower abdomen and parts of the chest. The second patient was a 62-year-old male with psoriasis and extensive arthritis who presented with prominent telangiectasias on the left lateral distal thigh with mild overlying epidermal atrophy. The third patient was an 80-year-old male with atrial fibrillation who presented with blanching, telangiectatic areas on the abdomen, thighs and back. Histologically, the skin lesions showed ectatic superficial small blood vessels with laminated, hyalinized concretions around vessels that were highlighted with periodic acid-Schiff staining following diastase digestion and reactive by immunohistochemical staining with an antibody to collagen type IV. CCV is a rare and poorly understood entity with distinct histopathological features that may clinically resemble generalized essential telangiectasia (GET), yet which may affect a different demographic population than GET. Awareness of this uncommon entity may further help to elucidate its etiology.

Melanocytic lesions of the conjunctiva.

CONTEXT: Melanocytic proliferations are among the most common neoplasms of the conjunctiva. They often represent challenging lesions for pathologists unfamiliar with unique histologic features of melanocytic proliferations in this location and with nomenclature used by ophthalmologists. OBJECTIVE: To comprehensively review clinical aspects, pathologic features, and management of melanocytic proliferations of the conjunctiva. DATA SOURCES: Review of the literature and personal experience of the authors. CONCLUSIONS: Classification, state of the art, and practical aspects of pathology of melanocytic proliferations of the conjunctiva are discussed.

Effect of tumor characteristics and duplication of the muscularis mucosae on the endoscopic staging of superficial Barrett esophagus-related neoplasia.

Endoscopic mucosal resection (EMR) is being advocated as a diagnostic, staging, and therapeutic technique for the management of Barrett esophagus (BE)-related neoplasia. With the emergence of new endoluminal therapy including EMR for the treatment of BE-related superficial adenocarcinomas, accurate staging has become crucial to select patients for different treatment arms. Intramucosal adenocarcinomas can be successfully treated by endoluminal techniques, whereas submucosal invasive tumors with a greater risk of lymph node metastasis are likely candidates for esophagectomy. Endoscopic ultrasound (EUS) is used to stage superficial BE-related neoplasms, yet endoscopic staging can be incongruent to that obtained after pathologic examination. In this study, we sought to determine morphologic factors, which may influence EUS staging in 35 cases with intramucosal adenocarcinoma diagnosed by subsequent EMR, focusing on tumor characteristics and structural changes associated with BE. Among the latter duplication of the muscularis mucosae, either fragmented or well-organized, was seen in 64% of 11 cases that were overstaged as having submucosal invasion by EUS, compared with 38% of those accurately staged. A greater vertical thickness of the tumor was also associated with overstaging by EUS (1.61+/-0.75 mm in the discordant vs. 1.16+/-0.67 mm in the concordant groups, P=0.028). The results illustrate how morphologic factors may affect EUS staging of superficial esophageal adenocarcinomas. EUS alone is not sufficient for staging these neoplasms precisely, and to accurately stratify patients into different treatment arms, EMR should play a role as a complementary staging modality.

Pigmented epithelioid melanocytoma: favorable outcome after 5-year follow-up.

Pigmented epithelioid melanocytoma (PEM) is a recently described entity encompassing epithelioid blue nevus (of Carney complex) and most tumors earlier considered as so-called "animal-type melanoma". Loss of expression of a Carney complex gene, cyclic adenosine 3',5' monophosphate-dependent protein kinase regulatory subunit 1alpha, is observed in the majority of PEMs. Initial reports with short-term follow-up have suggested that although PEMs frequently metastasize to lymph nodes, they have a more favorable outcome than conventional melanomas. In this report, we present the results of long-term follow-up in 26 patients with PEMs from North America and Australia. There were 9 males and 17 females, with a median age of 20 years. The tumors involved the trunk (6 cases), extremities (12 cases), genitalia (1 case), and the head and neck region (7 cases) had a median Breslow thickness of 2.2 mm (range 0.80 to 10.0 mm) and a median Clark level of 4. Eight of the patients developed lymph node metastases. After a median follow-up period of 67 months (range 39 to 216 mo), all patients are alive and free of disease. These findings provide further evidence that PEM is a unique low-grade melanocytic tumor with limited metastatic potential (to lymph nodes), but a favorable long-term clinical course.

Nephrogenic systemic fibrosis: a pathologic study of autopsy cases.

CONTEXT: -Nephrogenic systemic fibrosis (NSF) is a rare but serious disorder initially described as a purely dermatologic process. Isolated autopsy reports have described multiorgan involvement by this disease. OBJECTIVE: -To further illustrate the varied and systemic involvement of NSF by describing the autopsy experience at the Massachusetts General Hospital. DESIGN: -We describe the findings in a series of 4 autopsy cases of patients diagnosed with NSF. This report describes the history of renal dysfunction, exposure to gadolinium-containing contrast agents, specific laboratory parameters, and the extent of systemic involvement identified by postmortem examination. RESULTS: -Causes of death included systemic thromboembolic disease (n = 3) and pneumonia (n = 1). Laboratory parameters and type, dose, or timing of gadolinium-containing contrast-agent exposure did not correlate with clinical findings and outcomes. All patients demonstrated cutaneous manifestations of the disease and nephrocalcinosis, with some exhibiting calcification and fibrosis of the dura, thyroid, and heart including the cardiac conduction system, on postmortem examination. Soft tissue calcification was associated with concurrent hyperparathyroidism or high serum parathyroid hormone levels. CONCLUSIONS: -Thromboembolic disease can be a significant clinical complication of NSF. Patients with NSF may also develop characteristic histologic features of fibrosis and calcification in multiple organs, with significant morbidity and mortality. This autopsy series highlights the variability of systemic manifestations of NSF.

Organizing pneumonia and pulmonary lymphatic architecture in diffuse alveolar damage.

Diffuse alveolar damage represents the pathologic basis of most cases of the acute respiratory distress syndrome. Diffuse alveolar damage reflects injury to the pulmonary alveolar wall and microvasculature, leading to the exudation of water and plasma proteins that can overwhelm the local lymphatic drainage. Organizing pneumonia is a prominent histopathologic feature in some cases of diffuse alveolar damage. We examined whether diffuse alveolar damage-organizing pneumonia and changes in lymphatic architecture might be indicators of clinical outcome in acute respiratory distress syndrome. Formalin-fixed lung sections (n = 26) from thoracoscopic lung biopsies of patients with diffuse alveolar damage in the fibroproliferative phase, with or without organizing pneumonia, were immunostained with anti-CD31 and anti-D240, markers of vascular and lymphatic endothelium, respectively, and examined by morphometric analysis. Positively staining vessels were enumerated and maximal luminal diameters recorded in randomly selected low-power fields. Patients with diffuse alveolar damage-organizing pneumonia showed greater survival than those with diffuse alveolar damage (67% versus 33%, P = .03). The maximal luminal diameter of D240+ lymphatic vessels was larger for diffuse alveolar damage-organizing pneumonia than diffuse alveolar damage (28 +/- 4 versus 59 +/- 16 microm, P = .02). In addition, larger lymphatic luminal diameters (28 +/- 4 versus 47 +/- 11 microm) were associated with increased survival (P = .12). We conclude that lung biopsy histopathology and pulmonary lymphatic morphology may predict survival in acute respiratory distress syndrome.

Megakaryocytes and platelet homeostasis in diffuse alveolar damage.

Platelet homeostasis reflects a balance between the production of platelets via cytoplasmic fragmentation of megakaryocytes in the pulmonary microvasculature and their catabolism. Increased numbers of megakaryocytes are entrapped in the injured lung, potentially affecting circulating platelet counts. We enumerated pulmonary megakaryocytes and blood platelets in patients with diffuse alveolar damage (DAD) in order to determine their association with clinical outcome. Lung biopsies were examined from 21 patients with histologically documented DAD in its proliferative phase and secondary to a variety of causes. Blood platelet counts were determined within 24 h prior to lung biopsy, and CD61+ pulmonary megakaryocytes were localized in in situ immunohistochemical stains. The overall mortality in this series was 67%. Patients with DAD attributable to drug toxicity (DAD-D) had higher mortality (80%) and greater number of intrapulmonary CD61+ megakaryocytes than those with DAD due to other causes (23+/-7, 10+/-2, p<0.05). Patients with blood platelet counts =350 th/cm(3) showed increased survival (p<0.05). The findings support the hypothesis that abnormal platelet homeostasis is associated with increased mortality in acute lung injury and indicate that thrombocytosis in ARDS is associated with improved survival. The mechanisms of altered platelet homeostasis in DAD merit further investigation.