The Reemergence of Measles.

OBJECTIVES: Present-day pathologists may be unfamiliar with the histopathologic features of measles, which is a reemerging disease. Awareness of these features may enable early diagnosis of measles in unsuspected cases, including those with an atypical presentation. Using archived tissue samples from historic patients, a unique source of histopathologic information about measles and other reemerging infectious diseases, we performed a comprehensive analysis of the histopathologic features of measles seen in commonly infected tissues during prodrome, active, and late phases of the disease. METHODS: Subspecialty pathologists analyzed H&E-stained slides of specimens from 89 patients accessioned from 1919 to 1998 and correlated the histopathologic findings with clinical data. RESULTS: Measles caused acute and chronic histopathologic changes, especially in the respiratory, lymphoid (including appendix and tonsils), and central nervous systems. Bacterial infections in lung and other organs contributed significantly to adverse outcomes, especially in immunocompromised patients. CONCLUSIONS: Certain histopathologic features, especially Warthin-Finkeldey cells and multinucleated giant cells without inclusions, allow pathologists to diagnose or suggest the diagnosis of measles in unsuspected cases.

Cutaneous Actinomycosis of the Perineum in an Immunocompetent Man.

ABSTRACT: We present a case of primary cutaneous actinomycosis of unclear pathogenesis. A 30-year-old-man with no significant medical or surgical history presented to the emergency department with a 2-week history of a tender perineal mass. The patient denied trauma or perforating injury to the area. Examination of the area revealed an indurated, nonfluctuant, erythematous papulonodule located 2 cm from the anus. The lesion was unresponsive to oral and topical antibiotics and was therefore excised. The excision specimen revealed a dense mixed infiltrate partially filling the reticular dermis and extending into the subcutaneous fat. The infiltrate surrounded grains of basophilic material with an outer rim of eosinophilic radiating Splendore-Hoeppli material. Within the grains, filamentous bacteria were highlighted with Periodic acid-Schiff and Grocott's methenamine silver. The organisms were gram-positive and acid-fast negative. Given the clinical and histopathologic findings, actinomycosis was diagnosed. Two weeks later, the patient reported resolution of symptoms. The patient was lost to follow-up. This case highlights an unusual presentation of actinomycosis and the crucial role histopathology plays in diagnosis.

Atraumatic forearm swelling in a patient with poorly controlled asthma.

We present a case of sarcoidosis presenting as unilateral forearm swelling. A 65-year-old male with a long history of asthma presented with unexplained left forearm and hand swelling. Over many years, chest imaging had been devoid of adenopathy or parenchymal findings suspicious for sarcoid, until after the extremity findings emerged. The patient was diagnosed based on subcutaneous, dermal and mediastinal lymph node histopathology. Sarcoid presenting with isolated extremity findings prior to more typical pulmonary manifestations is rare even for cutaneous or soft tissue sarcoid, highlighting the need to maintain a high index of suspicion for sarcoidosis.

Molecular Detection of Filamentous Fungi in Formalin-Fixed Paraffin-Embedded Specimens in Invasive Fungal Wound Infections Is Feasible with High Specificity.

Trauma-related invasive fungal wound infections (IFIs) are associated with significant morbidity and mortality. Early identification and treatment are critical. Traditional identification methods (e.g., fungal cultures and histopathology) can be delayed and insensitive. We assessed a PCR-based sequencing assay for rapid identification of filamentous fungi in formalin-fixed paraffin-embedded (FFPE) specimens obtained from combat casualties injured in Afghanistan. Blinded FFPE specimens from cases (specimens positive on histopathology) and controls (specimens negative on histopathology) were submitted for evaluation with a panfungal PCR. The internal transcribed spacer 2 (ITS2) region of the fungal ribosomal repeat was amplified and sequenced. The PCR results were compared with findings from histopathology and/or culture. If injury sites contributed multiple specimens, findings for the site were collapsed to the site level. We included 64 case subjects (contributing 95 sites) and 102 controls (contributing 118 sites). Compared to histopathology, panfungal PCR was specific (99%), but not as sensitive (63%); however, sensitivity improved to 83% in specimens from sites with angioinvasion. Panfungal PCR identified fungi of the order Mucorales in 33 of 44 sites with angioinvasion (75%), whereas fungal culture was positive in 20 of 44 sites (45%). Saksenaea spp. were the dominant fungi identified by PCR in specimens from angioinvasion sites (57%). Panfungal PCR is specific, albeit with lower sensitivity, and performs better at identifying fungi of the order Mucorales than culture. DNA sequencing offers significant promise for the rapid identification of fungal infection in trauma-related injuries, leading to more timely and accurate diagnoses.

A new worm infiltrating the human cornea: A report of three cases.

PURPOSE: To characterize a new species of parasitic nematode that triggers uveitis. OBSERVATIONS: Three previously healthy, relatively young people each contracted a corneal stromal nematode that, upon surgical removal and examination, did not match any known nematodes. Clinical ocular findings included corneal opacification, visible corneal worms, conjunctival injection, and uveitis. CONCLUSIONS AND IMPORTANCE: The three cases presented here represent a previously undescribed parasitic infection of the cornea by an unidentified nematode. These findings may represent a previously unrecognized zoonotic infection from wildlife sources and potentially a newly documented nematode requiring description. Future clinical findings regarding this newly described nematode are needed to further develop our understanding of the disease.

Surgical Pathologic Diagnosis.

Surgical pathology results can play a crucial role in the management of immunocompromised patients. Here we highlight factors that differ between immunocompromised and immunocompetent hosts, such as variation in inflammatory response. Conditions that are covered include drug reactions, disease within solid organ allografts, immune reconstitution inflammatory syndrome, specific immunodeficiency syndromes, neoplasms related to viral infections, and viral, bacterial, fungal, and parasitic infections. Special techniques including immunohistochemistry, in situ hybridization and molecular detection of pathogen nucleic acid from formalin-fixed, paraffin-embedded tissue are discussed.

Epitrochlear cat scratch disease: unique imaging features allowing differentiation from other soft tissue masses of the medial arm.

OBJECTIVE: Evaluate anatomic and imaging features of epitrochlear regional adenopathy secondary to cat scratch disease (CSD) to assist differentiation of CSD from other soft tissue masses at the elbow. MATERIALS AND METHODS: Retrospective review of 24 confirmed cases of CSD. Patient demographics, clinical presentation and radiographic (R; n = 10), CT (n = 3), ultrasound (US; n = 5), and MR (n = 21) images were reviewed. Lesion location, size, number of masses, and intrinsic characteristics on R/CT/US/MR and presence of soft tissue inflammatory changes or adjacent bone or joint involvement were established through the consensus interpretation by four musculoskeletal radiologists. RESULTS: The average patient age was 18.6 years. Mass location was anterior and superficial to the medial intermuscular septum (100 %) with the masses posterior or posteromedial to the basilic vein (92 %). Three or fewer lymph nodes were involved in 92 %. Masses were noncalcified with adjacent inflammatory change (R = 90 %, CT = 100 %). US showed hypoechoic soft tissue echogenicity masses with defined to minimally irregular margins (80 %) and preserved central hilar hypervascularity on Doppler (100 % of cases). On MR, masses were T1 isointense (62 %), T2 isointense (54 %), intermediate signal on T2 images with fat suppression (55 %), and had perilesional inflammatory changes (95 %), perilesional fluid collections (38 %), adjacent muscle edema (81 %), hyperintense cental hilar vascular enhancement (65 %) and occasional preserved central hilar fat (14 %). CONCLUSION: Cat scratch disease is suggested by the characteristic location of a medial epitrochlear mass superficial to the brachial fascia and posterior to the basilic vein with surrounding inflammatory changes and preservation of hilar vascular architecture, hilar enhancement and occasional hilar fat.

Donor-derived transmission events in 2013: a report of the Organ Procurement Transplant Network Ad Hoc Disease Transmission Advisory Committee.

BACKGROUND: The Organ Procurement Transplant Network Disease Transmission Advisory Committee (DTAC), a multidisciplinary committee, evaluates potential donor-derived transmission events (PDDTE), including infections and malignancies, to assess for donor transmitted events. METHODS: Reports of unexpected PDDTE to Organ Procurement Transplant Network in 2013 were fully reviewed by DTAC. A standardized algorithm was used to assess each PDDTE from a given donor and to classify each individual recipient from that donor. RESULTS: Of 443 total PDDTE submitted, 159 were triaged and not sent out to the full DTAC. Of 284 fully evaluated reports, 32 (11.3%) resulted in a proven/probable (P/P) transmission of infection, malignancy or other conditions to 42 recipients. Of 204 infection events, 24 were classified as P/P affecting 30 recipients, with four deaths. Bacteria were the most frequently reported type of infection, accounting for 99 reports but only 12 recipients from 11 donors experienced P/P transmission. There were 65 donors reported with potential malignancy events and 5 were classified as P/P transmissions with 8 affected recipients and 2 deaths. Additionally, there were 16 noninfection, nonmalignancy reports resulting in 3 P/P transmissions to 4 recipients and 1 death. CONCLUSIONS: There was a 43% increase in the number of PDDTE reported and reviewed in 2013 over 2012. However, the percent with P/P transmission remains low, affecting recipients from 32 donors especially when compared with the more than 14,000 donors recovered annually in the United States. The continued use of the new standard algorithm and triaging process will enhance the reproducibility of DTAC assessments and allow more robust analysis of our aggregate DTAC experience.

From the radiologic pathology archives imaging of osteonecrosis: radiologic-pathologic correlation.

Osteonecrosis is common and represents loss of blood supply to a region of bone. Common sites affected include the femoral head, humeral head, knee, femoral/tibial metadiaphysis, scaphoid, lunate, and talus. Symptomatic femoral head osteonecrosis accounts for 10,000-20,000 new cases annually in the United States. In contradistinction, metadiaphyseal osteonecrosis is often occult and asymptomatic. There are numerous causes of osteonecrosis most commonly related to trauma, corticosteroids, and idiopathic. Imaging of osteonecrosis is frequently diagnostic with a serpentine rim of sclerosis on radiographs, photopenia in early disease at bone scintigraphy, and maintained yellow marrow at MR imaging with a serpentine rim of high signal intensity (double-line sign) on images obtained with long repetition time sequences. These radiologic features correspond to the underlying pathology of osseous response to wall off the osteonecrotic process and attempts at repair with vascularized granulation tissue at the reactive interface. The long-term clinical importance of epiphyseal osteonecrosis is almost exclusively based on the likelihood of overlying articular collapse. MR imaging is generally considered the most sensitive and specific imaging modality both for early diagnosis and identifying features that increase the possibility of this complication. Treatment subsequent to articular collapse and development of secondary osteoarthritis typically requires reconstructive surgery. Malignant transformation of osteonecrosis is rare and almost exclusively associated with metadiaphyseal lesions. Imaging features of this dire sequela include aggressive bone destruction about the lesion margin, cortical involvement, and an associated soft-tissue mass. Recognizing the appearance of osteonecrosis, which reflects the underlying pathology, improves radiologic assessment and is important to guide optimal patient management.

From the radiologic pathology archives: ewing sarcoma family of tumors: radiologic-pathologic correlation.

The Ewing sarcoma family of tumors includes osseous Ewing sarcoma, extraskeletal Ewing sarcoma, primitive neuroectodermal tumor, and Askin tumor. They share a karyotype abnormality with translocation involving chromosomes 11 and 22. Histologically, these lesions demonstrate crowded sheets of small round blue cells. Imaging features of osseous Ewing sarcoma often suggest the diagnosis, with aggressive long-bone destruction in the metadiaphysis of an adolescent or young adult and an associated soft-tissue mass. Focal areas of cortical destruction are frequent, allowing continuity between the intraosseous and extraosseous components. This continuity is also commonly seen as subtle channels extending through the cortex at computed tomography or magnetic resonance (MR) imaging, a finding that reflects the underlying pathologic appearance. Extraskeletal Ewing sarcoma commonly demonstrates a nonspecific radiologic appearance of a large soft-tissue mass affecting the paraspinal region or lower extremity. Askin tumor represents extraskeletal Ewing sarcoma involving the chest wall. Imaging typically reveals a large pleural-based mass and associated pleural effusion. Treatment of these tumors is usually a combination of neoadjuvant chemotherapy followed by surgical resection, which may be supplemented with radiation therapy. Imaging, particularly MR, is also vital to evaluate response to neoadjuvant therapy, direct surgical resection, and detect local recurrence or metastatic disease.

Conidiobolomycosis in a young Malaysian woman showing chronic localized fibrosing leukocytoclastic vasculitis: a case report and meta-analysis focusing on clinicopathologic and therapeutic correlations with outcome.

BACKGROUND: Conidiobolomycosis (also known as rhinoentomophthoramycosis) is a rare cutaneous/mucosal fungal infection seen mainly in the tropical rain forest regions of the world that can be associated with disfiguring facial elephantiasis, and rarely, death. OBJECTIVE: To present an exemplary case report and perform a systematic review of the world's literature to more accurately describe the natural history and the effect of therapy on outcome in conidiobolomycosis. METHODS: Case report and meta-analysis of published case reports and series of conidiobolomycosis to determine which clinical, pathologic, mycologic, and treatment factors impact on prognosis. RESULTS: We document delay in diagnosis of conidiobolomycosis in a young Malaysian woman, whose biopsy showed pathognomonic features-massive tissue eosinophilia and Splendore-Hoeppli phenomenon surrounding broad hyphae. These findings coexisted with granuloma faciale-like changes (fibrosing leukocytoclastic vasculitis) and lymphedema. Treatment with multiple antifungals was followed by complete resolution. For the meta-analysis, pooled data from 199 cases (162 with full outcome data) from 120 reports revealed a similar course for most cases: a disease affecting healthy young adults who present with progressive nasal symptoms (eg, nasal obstruction) and central facial swelling and show improvement or cure after surgical excision and/or treatment with one or more antifungal agents in 83%. Persistent-progressive facial disease occurred in 11%, and 6% died rapidly of fungal infection. Presentation with facial elephantiasis correlated with persistent-progressive rhinoentomophthoramycosis and a longer duration of disease before diagnosis (P = 0.02). Lethal infections were significantly associated with nonstereotypical presentation (eg, orbital cellulitis), visceral infection, absence of the Splendore-Hoeppli phenomenon, presence of comorbidities (eg, immunosuppression, hematolymphoid malignancy), infection with Conidiobolus incongruus or Conidiobolus lamprauges (not Conidiobolus coronatus), lack of response to amphotericin B, and female sex (all P ≤ 0.002). The few sensitivity studies performed demonstrated in vitro multidrug resistance of Conidiobolus species to most available antifungal agents. LIMITATIONS: Publication bias, reporting heterogeneity, and data deficits may affect results. CONCLUSIONS: Conidiobolomycosis should be included in the differential diagnosis of patients who present with nasal symptoms and painless centrofacial swelling. Massive tissue eosinophilia and Splendore-Hoeppli material coating thin-walled hyphae confirms the clinical diagnosis. The granuloma faciale-like histology found in this case can explain the onset of facial lymphedema by fibroinflammatory destruction of lymphatic vessels; the duration of disease and severity of inflammation likely predicts whether the lymphedema is reversible or not. Although rhinoentomophthoramycosis ostensibly responds in vivo to most available antifungal agents, routine culture and susceptibility testing is recommended to better define the efficacy of these therapeutic agents.

Soft tissue Rosai-Dorfman disease: 29 new lesions in 18 patients, with detection of polyomavirus antigen in 3 abdominal cases.

Soft tissue Rosai-Dorfman disease (STRDD) is rare, previously reported only as single cases and few series. Simian virus 40 (SV40), a polyomavirus, has been identified in lymphoid processes and has a controversial role in neoplasia etiology. Occasional cytoplasmic pink granular inclusions and nuclear changes led us to explore a viral etiology. Only unpublished STRDD from our files with adequate material, soft tissue location, and diagnostic confirmation were included. Immunohistochemistry and follow-up were obtained. Eighteen STRDD patients, 4 male and 14 female, had 29 lesions; 5 with 2 or more lesions. Ages ranged from 8 to 81 years (mean 42.6 years and median 42.5 years). Soft tissue Rosai-Dorfman disease locations include trunk or proximal extremity (n = 19), distal extremity (n = 5), "abdominal" (n = 3), face (n = 1), and unknown subcutaneous site (n = 1). Sizes ranged from 0.5 to 13.7 cm (median, 2.4 cm). Previous disease included lymphoma, buttocks injection site, diabetes and hypothyroidism, and radiation for chronic dermopathy. No patients had a preceding or concurrent known viral infection; none had lymphadenopathy at present. None were known to be immunocompromised. Soft tissue Rosai-Dorfman disease was rapidly progressing. Initial pathologic diagnosis ranged from Rosai-Dorfman disease or inflammatory pseudotumor to inflammatory malignant fibrous histiocytoma. Grossly STRDDs were multilobulated, tan-yellow, and firm; morphologically, circumscribed, and subcutaneous-based. All had sheets of polygonal histiocytes with abundant pale eosinophilic cytoplasm, emperipolesis, plasma cells, and lymphocytes scattered and within clusters. Focal spindle cell change and mild pleomorphism were each observed in 3 patients; 2 had focal necrosis, none with mitoses. Small granular pink cytoplasmic inclusions and nuclear viral-like changes were observed. By immunohistochemistry, all STRDDs were positive for S100 protein, negative for CD1a, Epstein-Barr virus, and latent membrane protein, yet 3 (all abdominal, 1 multicentric) of the 9 studied were focally positive for cytoplasmic and nuclear SV40 polyomavirus. All were treated by local excision. Follow-up on 14 patients older than 8 to 16 years revealed recurrence in 3 patients with persistent multiple lesions, one with abdominal location. There were no metastases or death from disease. Soft tissue Rosai-Dorfman disease is a rapidly evolving, mostly solitary and nonrecurrent trunk and proximal extremity subcutaneous lesion in middle-aged females. More than one third can have persistent multicentric disease. It is important to recognize STRDD, to separate it from malignancy. Epstein-Barr virus/latent membrane protein was negative but polyomavirus was positive in 3 patients with abdominal STRDD, one with multicentric persistent disease. The relationship of polyomavirus to the evolution of abdominal STRDD should be further explored.

Granulomatous reaction to pneumocystis jirovecii: clinicopathologic review of 20 cases.

To better characterize the clinical and pathologic features of granulomatous reaction to Pneumocystis jirovecii, we reviewed 20 cases of this uncommon response. Patients included 15 males and 5 females (mean age 52 y). The most common symptom was dyspnea (5 of 14). Primary medical diagnoses included human immunodeficiency virus/acquired immunodeficiency syndrome (7 of 20), hematopoietic (6 of 20), and solid malignancies (4 of 20). Radiology findings included nodular (8 of 16) and diffuse (5 of 16) infiltrates and solitary nodules (3 of 16). Diagnostic procedures with the highest yield were open lung biopsy (13 of 20) and autopsy (5 of 20); false-negative results were most common on bronchial washings/brushings, bronchoalveolar lavage, fine needle aspiration, and transbronchial biopsy. Follow-up showed resolution of disease (6 of 13), death from disease (6 of 13), and death from unknown cause (1 of 13). Histologically, clusters of Gomori methenamine silver-positive (20 of 20) Pneumocystis organisms were identified in all cases. Organisms were identified within well (16 of 20) and poorly (4 of 20) formed necrotizing (16 of 20) and non-necrotizing (4 of 20) granulomas ranging in size from 0.1 to 2.5 cm (mean 0.5 cm); granulomas were multiple (18 of 20) or single (2 of 20). Giant cells (11 of 20), a fibrous rim (8 of 20), and eosinophils (6 of 20) were seen. Foamy eosinophilic exudates were present centrally within some granulomas (5 of 20). Cystic spaces (1 of 20) and calcification (1 of 20) were rare. Only one case demonstrated classic intra-alveolar foamy exudates containing Pneumocystis. Granulomatous P. jirovecii pneumonia occurs most commonly in males with human immunodeficiency virus/acquired immunodeficiency syndrome, hematopoietic, and solid malignancies. The diagnosis may be overlooked as conventional radiologic and pathologic features are absent. When suspected, open lung biopsy is most likely to yield diagnostic material. Attention to organism morphology avoids misdiagnosis as Histoplasma.

Deposition of calcium salts in a case of pulmonary zygomycosis: histopathologic and chemical findings.

We report a case of pulmonary zygomycosis associated with unusual deposition of calcium salt crystals. The patient was a 75-year-old female who had onset of cough and shortness of breath. She was treated for community-acquired pneumonia but died despite intensive therapy. Postmortem examination revealed diffuse alveolar damage and multifocal necrotizing pneumonia associated with herpes simplex infection and invasive zygomycosis. Birefringent particles were seen associated with fungal elements in the lung parenchyma, within bronchial cartilage, and in blood vessel walls. By infrared spectroscopy, the birefringent particles in the pulmonary parenchyma and within bronchial cartilage had spectral characteristics of calcium oxalate dihydrate and calcium oxalate monohydrate, respectively. The birefringent crystals within vascular walls were identified as calcium carbonate. This case documents the chemical composition and location of 3 different calcium salt crystals in pulmonary zygomycosis. It also shows that among pulmonary fungal infections, calcium oxalate deposition is not restricted to aspergillosis.

Borderline tuberculoid leprosy in a woman from the state of Georgia with armadillo exposure.

In the southern and southeastern United States, the 9-banded armadillo is an important reservoir for Mycobacterium leprae, the causative agent of leprosy (Hansen's disease). Here, we describe a woman living in Georgia with borderline tuberculoid leprosy who worked for many years in a garden where armadillos burrowed or were buried. There was no history of foreign travel or known exposure to a person with leprosy. Treatment with 6 once-monthly combined doses of rifampin, ofloxacin, and minocycline was successful.

Fungi as bioweapons.

Fungi cause disease directly by infection or indirectly through mycotoxins. Fungi that are used as weapons might be targeted against humans, livestock, or crops. Humans and animals encounter fungi and mycotoxins through inhalation, ingestion, and contact with skin and mucous membranes. Effective fungal bioweapons would require the ability to cause significant destruction and a means of delivery to target populations or farms. Effective counter measures against fungal bioweapons would be able to prevent or treat this damage. This article describes several potential biological warfare or bioterrorism fungal species and mycotoxins in regard to their biology, epidemiology, potential for weaponization, and the clinical features, prevention, and treatment of the diseases that they cause.