Acral Papulovesicular Eruption in a Soldier Following Smallpox Vaccination.

Smallpox vaccination is associated with several potential cutaneous adverse reactions, ranging from benign self-limited hypersensitivity reactions to life-threatening eczema vaccinatum and progressive vaccinia. Acral papulovesicular eruption is a distinct presentation that has been described in US Military service members following vaccination with the second-generation smallpox vaccine (ACAM2000, Sanofi Pasteur Biologics Co). We describe a case of this unique cutaneous eruption and review previously described cutaneous adverse events associated with smallpox vaccination.

Cutaneous Leishmaniasis in a Saudi Arabian Soldier Stationed in the United States.

BACKGROUND: Leishmaniasis is a common parasitic disease seen in many parts of the world, especially in areas where current U.S. and international forces are deployed. Approximately 350 million people are thought to be at risk of cutaneous leishmaniasis (CL) with an annual incidence of 1.5 million cases. Over 90% of cutaneous infections with Leishmania occur in the Middle East, Brazil, and Peru. Outbreaks of CL may occur in military personnel deployed to endemic areas. Since the incubation period for symptomatic CL ranges from weeks to months, symptoms may not appear until well after returning to the United States. As operations continue to expand globally, the exposure and concern for leishmaniasis persists for military physicians. We describe localized CL in a previously healthy male in an effort to help medical personnel identify leishmaniasis on the basis of cutaneous lesions alone, as well as increase diagnostic suspicion when treating patients in nonendemic areas. RESULTS: A previously healthy 30-year-old Saudi Arabian male presented to the emergency department with a 1-month history of four well-demarcated nonhealing, painless ulcers on his left ear, hand, and foot. Symptoms began shortly after arriving in the United States. He had been treated with trimethoprim/sulfamethoxazole, oral clindamycin, mupirocin ointment, and vancomycin for suspected infection without improvement of lesions. Upon presentation to dermatology, physical examination revealed a firm erythematous plaque with central ulceration on his left ear. Two shallow indurated ulcers were also found on his left fourth dorsal finger and left dorsal foot. Biopsy of the foot revealed granulomatous inflammation with predominantly lymphoplasmacytic infiltrate and multinucleated giant cells. Parasitized histiocytes were identified on hematoxylin and eosin stain and focally on Giemsa stain. Polymerase chain was consistent with a diagnosis of leishmaniasis and outpatient treatment was initiated with fluconazole 200 mg daily for 6 weeks. At 2-week follow-up, lesions were noted to be stabilized. DISCUSSION: CL has a wide variety of presentations. The classic lesion appears as a papule that will enlarge, often developing into a nodule or plaque-like lesion with central ulceration. The lesion may be covered with an eschar or by fibrinous material. This presentation can mimic many disease processes resulting in an extensive differential diagnosis that includes bacterial, fungal, and viral infections, cutaneous malignancy, and insect bites. The clinical course, treatment options, response to therapy, and prognosis are all highly variable and dependent on the causative species. Local therapy options, oral systemic agents, and parenteral agents have all shown varying results in the treatment of leishmaniasis. The difficulty with standardizing treatment options for CL stems from the lack of well-controlled studies and the lack of standardized outcome measures. This deficiency in comparative studies of treatment hinders consensual recommendations. However, the choice of the correct therapy often depends on the experience of the clinician, burden of disease, preferences of patients, and cost-effectiveness considerations for the patient and/or the health care system.

Aleukemic Myeloid Leukemia Cutis with a Kikuchi Disease-Like Inflammatory Pattern in Myelodysplastic Syndrome.

Myeloid leukemia cutis (MLC) is a rare disease characterized by the infiltration of neoplastic myeloid, myelomonocytic, or monocytic precursors into the skin, producing clinically nonspecific-appearing papules, nodules, plaques, or purpura that necessitate biopsy for definitive diagnosis. In general, it is considered an extramedullary manifestation of acute myeloid leukemia (AML) similar to myeloid sarcoma, also known as a chloroma. MLC often develops in patients with an established diagnosis of AML and is only rarely seen before the onset of systemic disease. Even more rarely, some patients are found to have an underlying nonleukemic bone marrow disease, such as a myelodysplastic syndrome (MDS). It is in these latter settings that the somewhat perplexing terminology aleukemic leukemia cutis (ALC) has been used widely. As may be imagined, establishing a diagnosis of ALC can be problematic and typically requires a high index of suspicion with careful integration of clinical, histopathological, and laboratory data. Once a diagnosis of ALC is made, a complete hematologic workup, including assessment of the patient's bone marrow, is essential because a diagnosis of MLC (with or without systemic leukemia) generally indicates a poor prognosis. When discovered in a patient with MDS, MLC has been suggested to herald progression toward more advanced disease. We present a rare case of so-called aleukemic myeloid leukemia cutis in an 82-year-old man subsequently diagnosed as having MDS without progression to overt AML. This case also illustrates a seemingly rare Kikuchi disease-like inflammatory pattern that obscured the underlying leukemic infiltrate in the skin, delaying its recognition.

Primary intra-renal desmoplastic small round cell tumor: expanding the histologic spectrum, with special emphasis on the differential diagnostic considerations.

Intra-abdominal desmoplastic small round cell tumor (DSRCT) is a rare, aggressive tumor affecting adolescent and young males. DSRCT presenting as a primary renal mass in the absence of visceral or serosal involvement is extremely rare. Herein, we present the pathologic and molecular findings in the case of a young man who presented with a large renal mass without any visceral or serosal involvement. Noticeably, the tumor lacked prominent desmoplastic stroma and only focally expressed cytokeratin, both of which are considered characteristic histologic features for this tumor. Fluorescence in situ hybridization studies using an EWSR1 break-apart probe confirmed the presence of a rearrangement involving the EWSR1 locus and RT-PCR demonstrated the presence of an EWSR1-WT1 fusion transcript associated with the t(11;22) rearrangement, which supported a diagnosis of DSRCT. We also discuss the differential diagnostic considerations faced by the pathologist in the workup of small round cell neoplasms of the kidney.

Re-examination of features to distinguish polyarteritis nodosa from superficial thrombophlebitis.

The correct identification of vessel type is crucial in distinguishing cutaneous polyarteritis nodosa from superficial thrombophlebitis. As the treatment and prognosis of these conditions are very different, correct diagnosis is critical, but they have overlapping clinical and histopathologic features, which can sometimes make the distinction difficult. Features commonly used to distinguish an artery from vein include vessel shape and diameter, the presence or absence of an internal elastic lamina, smooth muscle pattern, and the presence or absence of valves. Recently, it has been proposed that the amount and distribution of elastic fibers in the medial muscular layer are the most reliable features to make this distinction. The first part of this study used prosector-identified vessels to determine which of these features is most sensitive and specific for identifying an artery and vein. A total of 19 arteries and 16 veins were dissected from autopsy and amputation specimens. For each specimen, the smooth muscle pattern, elastic fiber pattern, the presence of valves, and the presence or absence of an internal elastic membrane were determined. The quantity of elastic fibers in the muscular wall of each sample was also determined. Although the elastic fiber pattern was the most specific feature in identifying a vein, it suffered from low sensitivity (43.8%). The smooth muscle pattern had the highest combined sensitivity and specificity. In the second part of this study, the histologic features listed above were examined in previously diagnosed cases of superficial thrombophlebitis and arteritis. When inflammation is present within and around the wall of the vessel, all of the studied histologic features become less reliable, and the interobserver reliability of distinguishing arteritis from thrombophlebitis was low. Our findings suggest that no single histopathologic feature is completely reliable and combining the histopathologic features with clinicopathologic correlation is essential for correct vessel identification.

Gastroduodenal Cryptococcus in an AIDS Patient Presenting With Melena.

Gastrointestinal cryptococcosis is extremely rare with only a few case reports found in the literature and involvement primarily identified post-mortem. This is a case of 54-year-old man with a 20-year history of poorly controlled human immunodeficiency virus presented with constitutional symptoms along with melena. Diagnostic work up with esophagogastroduodenoscopy showed 4 irregular ulcers in the stomach notable for red-pigmented lesions within the ulcers, erythematous mucosa in the antrum and patchy friable mucosa in the duodenum. H&E staining and Mucicarmine staining showed findings consistent with C. neoformans. Blood culture and cerebrospinal fluid studies also revealed C. neoformans. Cryptococcus neoformans is an AIDS defining illness that most commonly presents as meningoencephalitis and pneumonitis. Key management principles includes: induction of antifungal therapy followed by consolidation and maintenance; management of elevated intracranial pressure and immune reconstitution inflammatory syndrome. Although the organism can infect nearly all organs, gastrointestinal involvement is rarely described. Our case highlights the fact that gastrointestinal C. neoformans infection can be associated with upper gastrointestinal symptoms and may be the initial presentation of disseminated cryptococcosis.

Smooth muscle pattern is more reliable than the presence or absence of an internal elastic lamina in distinguishing an artery from a vein.

BACKGROUND: Major pathology textbooks suggest that the shape of the vessel and the presence or absence of an internal elastic lamina are the best means to distinguish an artery from a vein. Because the shape of the vessel is highly dependent upon the plane of section, the internal elastic lamina is often cited as a more reliable criterion. After evaluating a patient with superficial thrombophlebitis, in whom these conventional criteria had led to a misdiagnosis of polyarteritis nodosa, we sought to determine whether the pattern of smooth muscle in the media is a more sensitive discriminator between an artery and a vein. METHODS: Anatomically identified arteries and veins were harvested from extremity amputation specimens and stored autopsy organ specimens and reviewed by two dermatopathologists who were blinded to the gross pathologist's impression. The biopsies were assessed for the smooth muscle pattern and the presence or absence of an internal elastic lamina. RESULTS: Forty-seven of the 50 cases (94%) were concordant with the pathologist's gross impression using only the smooth muscle pattern to differentiate an artery from a vein. On the basis of the presence or absence of an internal elastic lamina, 41 of 50 cases (82%) were concordant with the prosector's designation of the vessel. LIMITATIONS: Vessels were harvested from a variety of sites, with lower extremity vessels predominating. There may be some regional variability not addressed in this study. CONCLUSION: In this study, the pattern of muscle fibers within the vascular media discriminated between arteries and veins better than assessment of the presence or absence of an internal elastic lamina. Although no single criterion is 100% reliable, assessment of both these criteria may minimize the risk of misinterpreting vessels in the deep dermis and subcutis.

Safety of band ligator use in the small bowel and the colon.

BACKGROUND: Endoscopic band ligation for bleeding small-bowel vascular lesions has been reported as safe and efficacious based on small case series. There have been several other published case reports of band ligators used for bleeding lesions, usually Dieulafoy's lesions, in the stomach, the proximal small bowel, and the colon. In addition, this method has been used for postpolypectomy bleeding stalks. There has never been a critical look at the anatomic consequences of banding in the thinner sections of bowel. METHOD: The purpose of this study is to define the anatomic and histologic consequences of applying band ligator devices to the small and the large bowel. Fresh surgical specimens, both large and small bowel, that were excised because of neoplastic lesions were transported to our endoscopy unit where one end of the intact bowel was sutured shut. A standard upper endoscope was passed via the open end, and the bowel was closed tightly with rubber band ties. The bowel then was insufflated, and band ligators were applied to unaffected mucosa by using a standard technique. Photodocumentation from inside and outside the bowel was obtained. Some of the band polyps were cut above the band, and some were cut below the band in the fresh state. Some were fixed in formalin and examined microscopically. Histologic sectioning occurred at the level of the bands. RESULTS: The results were striking in that there were large holes (1 cm) in the fresh ileum specimen. There was gross serosal entrapment manifested by visible puckers on the outer surfaces of the specimens, especially in the small bowel and the right colon. The left colon, anatomically thicker, was less affected. The histologic evaluation revealed inclusion by the band ligator of the muscularis propria and serosa on the small bowel, the muscularis propria in the right colon, and the submucosa in the left colon. CONCLUSIONS: Based on these findings, we conclude that band ligator devices are not safe in the small bowel and the right colon but probably are safe in the thicker left colon.

A comparison of vertical versus transverse sections in the evaluation of alopecia biopsy specimens.

BACKGROUND: Both vertical and transverse sections are used in the histologic interpretation of alopecia biopsy specimens. Although a combination of the two may be optimal, the pathologist is frequently only provided with a single specimen. Even though the trend in recent years has been toward transverse sections in this setting, we are not aware of any published data directly comparing the two methods. METHODS: One hundred two consecutive archived hair biopsy accessions that demonstrated comparable vertical and transverse sections were examined twice, each time in a random order. The pathologist's interpretation based only on the vertical sections and an interpretation based only on the transverse sections were compared with the original biopsy report, which had been based on the combination of vertical and transverse sections. RESULTS: In 76 cases, all 3 diagnoses were concordant (ie, the diagnosis made with vertical sections alone, the diagnosis made with transverse sections alone, and the original diagnosis were all in agreement). In 2 cases, neither the diagnosis made with vertical sections alone nor the diagnosis made with transverse sections alone were in full agreement with the original diagnosis. In 20 cases, only the diagnosis made with vertical sections was concordant with the original diagnosis. In 4 cases, only the diagnosis made with transverse sections alone was concordant with the original diagnosis. LIMITATIONS: Our practice is heavily weighted toward scarring alopecia, and the results of our study may not be applicable to practices weighted toward other forms of alopecia. Because the cases had been signed out over a period of several years, the nomenclature for some entities changed. For the purposes of our study, we counted the diagnoses of follicular degeneration syndrome and idiopathic pseudopelade to be subtypes of (and concordant with) a diagnosis of central centrifugal cicatricial alopecia. In some cases, a definitive diagnosis was not possible at the time of the original diagnosis, but rather the pathologist had provided a histologic description and a differential diagnosis. For purposes of this study, an interpretation was considered to be concordant with the original descriptive diagnosis if all of the important histologic features were identified that had been described in the original report. Sampling error could have contributed to discordant diagnoses, but would be expected to affect both vertical and transverse samples in a random manner. CONCLUSION: The combination of vertical and transverse sections is superior to either alone. Although transverse sections have revolutionized the evaluation of alopecia, in this study, the diagnosis made with vertical sections alone had a higher concordance rate with the combination than did transverse sections alone. As there are advantages and disadvantages inherent in either method, when only a single biopsy specimen is submitted, it may be sectioned either vertically or transversely, at the discretion of the pathologist. With either method, serial step sections should be obtained to reduce the risk of missing important histologic findings.

The accuracy of the report of hepatic steatosis on ultrasonography in patients infected with hepatitis C in a clinical setting: a retrospective observational study.

BACKGROUND: Steatosis is occasionally reported during screening ultrasonography in patients with hepatitis C virus (HCV). We conducted a retrospective observational study to assess the factors associated with steatosis on ultrasonography and the relationship between steatosis on ultrasound versus biopsy in patients infected with HCV in a clinical setting. Our hypothesis was ultrasonography would perform poorly for the detection of steatosis outside of the context of a controlled study, primarily due to false-positive results caused by hepatic fibrosis and inflammation. METHODS: A retrospective review of ultrasound reports was conducted on patients infected with HCV in a tertiary care gastroenterology clinic. Reports were reviewed for the specific documentation of the presence of steatosis. Baseline clinical and histologic parameters were recorded, and compared for patients with vs. without steatosis. Multiple logistic regression analysis was performed on these baseline variables. Liver biopsies were reviewed by two pathologists, and graded for steatosis. Steatosis on biopsy was compared to steatosis on ultrasound report, and the performance characteristics of ultrasonography were calculated, using biopsy as the gold standard. RESULTS: Ultrasound reports were available on 164 patients. Patients with steatosis on ultrasound had a higher incidence of the following parameters compared to patients without steatosis: diabetes (12/49 [24%] vs. 7/115 [6%], p < 0.001), fibrosis stage > 2 (15/48 [31%] vs. 16/110 [15%], p = 0.02), histologic grade > 2 (19/48 [40%] vs. 17/103 [17%], p = 0.002), and ALT (129.5 +/- 89.0 IU/L vs. 94.3 +/- 87.0 IU/L, p = 0.01). Histologic grade was the only factor independently associated with steatosis with multivariate analysis. When compared to the histologic diagnosis of steatosis (n = 122), ultrasonography had a substantial number of false-positive and false-negative results. In patients with a normal ultrasound, 8/82 (10%) had > 30% steatosis on biopsy. Among patients with steatosis reported on ultrasound, only 12/40 (30%) had > 30% steatosis on biopsy review. CONCLUSION: Steatosis on ultrasound is associated with markers of inflammation and fibrosis in HCV-infected patients, but does not consistently correlate with steatosis on biopsy outside of the context of a controlled study. Clinicians should be skeptical of the definitive diagnosis of steatosis on hepatic ultrasonography.

Atypical junctional melanocytic proliferations in benign lichenoid keratosis.

Melanocytic lesions with lichenoid regression may mimic a benign lichenoid keratosis (BLK) histologically. A total of 336 BLKs were reviewed and deeper sections obtained to determine the frequency of this phenomenon. Two cases (0.6%) showed at least 1 melanocytic nest or junctional multinucleated melanocyte (starburst melanocyte) on deeper sections confirmed by MART-1 immunostaining. Both of these cases demonstrated solar elastosis, and 1 case had an effaced rete ridge pattern. Not included in the histological study are 5 additional cases in which the initial slide showed only lichenoid dermatitis, but deeper sections obtained before to the initial sign-out revealed a melanocytic proliferation. These 5 cases would have been signed out as "consistent with BLK" if deeper sections had not been obtained. Fluorescent in situ hybridization (FISH) was performed on 3 cases; in each case, the melanocytes demonstrated a loss of chromosome 9p21 DNA copy number. The finding of nests of genetically altered melanocytes on severely sun-damaged skin strongly suggests that these cases represent lichenoid regression of melanoma in situ. Pathologists should approach a diagnosis of BLK cautiously in the setting of severely sun-damaged skin.