This composite image consists of two panels illustrating clinical and pathological findings associated with scrub typhus and secondary hemophagocytic lymphohistiocytosis (HLH). Panel A is a clinical photograph of a child's shoulder region showing a pathognomonic eschar: a small, oval-shaped, necrotic cutaneous lesion with a dark, crusty center and minimal surrounding erythema. Panel B is a high-power light microscopy image of a bone marrow aspirate stained with Wright-Giemsa. It demonstrates hemophagocytosis, characterized by a large activated macrophage (histiocyte) containing engulfed hematopoietic elements, including nucleated red blood cells or leukocytes, within its cytoplasm. The image serves as an educational tool for identifying the primary diagnostic cutaneous sign of rickettsial infection (Orientia tsutsugamushi) alongside its potential systemic complication, hemophagocytic syndrome.

This composite medical image consists of three panels demonstrating clinical findings in a case of severe infection and systemic complications. (A) Anterior-posterior chest X-ray showing extensive, ill-defined heterogeneous opacification and consolidation in the middle and lower zones of the right lung field, consistent with severe pneumonia. (B) High-magnification bone marrow aspirate (Wright-Giemsa stain) revealing active hemophagocytosis, characterized by a large macrophage engulfing multiple hematopoietic cells, including erythrocytes and precursors, indicative of hemophagocytic lymphohistiocytosis (HLH). (C) Peripheral blood smear (Wright-Giemsa stain) showing numerous schistocytes (fragmented red blood cells) including helmet cells and triangular forms, alongside a loss of central pallor in some cells. These findings are diagnostic of microangiopathic hemolytic anemia (MAHA) secondary to thrombotic microangiopathy (TMA). Together, these panels illustrate the progression from a primary pulmonary infection to secondary multisystem hematologic pathologies including septic shock-induced HLH and ADAMTS-13 associated TMA.

A multi-panel medical figure displaying diagnostic findings for Hemophagocytic Lymphohistiocytosis (HLH). Panel A presents T1-weighted brain MRI scans with gadolinium enhancement in axial (left) and coronal (right) views, showing increased vessel enhancement in the cerebral sulci and bilateral dural thickening, indicative of an inflammatory process. Panel B contains high-power magnification (×1000) Wright-Giemsa stained bone marrow smears; arrows highlight activated macrophages exhibiting hemophagocytosis, specifically engulfing a nucleated cell (left) and platelets (right). Panel C shows sequential coronal abdominal CT scans demonstrating the progression from normal spleen size (left, day 12) to splenomegaly (right, day 18, 12.7 cm). Panel D is a clinical photograph of the torso showing diffuse petechiae. The composite illustrates the neurological, hematological, and systemic manifestations of secondary HLH, including aseptic encephalitis, cytopenias, and organomegaly.

Imaging modality and technique: Transmission Electron Microscopy (TEM); ultrastructural visualization of Birbeck granules within Langerhans cells. Specimen: routine biopsy tissue containing dendritic histiocytes from a suspected Langerhans cell histiocytosis lesion. Location: cutaneous/epidermal/dermal tissue; observed in situ cytoplasmic inclusions. Features: Birbeck granules are zipper-like, pentalaminar rods with a dilated terminal end producing a tennis racket shaped appearance. These cytoplasmic organelles measure approximately 200-400 nm in length and about 33 nm in width. The dilated distal end contains langerin (CD207) and is a hallmark ultrastructural feature of Langerhans cells. Comparative context: Birbeck granules distinguish Langerhans cells from other mononuclear phagocytes on TEM; however, modern diagnostics rely on immunohistochemical markers such as CD1a and CD207 (langerin), making TEM less routinely used today. Pathological significance: the presence of Birbeck granules supports a diagnosis of Langerhans cell histiocytosis when correlated with histology and IHC. Clinical correlation: LCH may present with bone lesions, skin rash, or organ involvement; TEM was historically the gold standard but is now largely supplanted by CD1a and langerin IHC, with ultrastructural confirmation reserved for academic or unresolved cases. Educational utility: illustrates classic ultrastructure of dendritic histiocytes and their diagnostic utility in pathology. This image emphasizes ultrastructural differentiation and context for learners.

Immunohistochemistry image of pulmonary tissue stained for CD1a demonstrating Langerhans cell histiocytosis. Modality: Immunohistochemistry (IHC) using CD1a primary antibody with DAB chromogen and hematoxylin counterstain. The specimen is lung parenchyma showing a dense cluster of mononuclear dendritic cells with characteristic irregular, reniform (coffee-bean) nuclei surrounded by a background of inflammatory cells. Strong, paranuclear and cytoplasmic CD1a positivity is evident as uniform brown membrane/cytoplasmic labeling of most lesional cells. Langerin (CD207) and S-100 would be co-expressed in the Langerhans cells, though not all panels may be shown in this image. The staining pattern and cellular morphology support the diagnosis of LCH in the pulmonary setting, where Langerhans cells form focal infiltrates and can be associated with smoking-related lung disease. Birbeck granules, while historically demonstrated by electron microscopy, are now replaced by the immunophenotype. This image emphasizes diagnostic specificity of CD1a positivity for identifying Langerhans cells within the alveolar/interstitial compartment. Clinically, pulmonary LCH is frequently linked to adult smokers and may present with nodules or cystic lesions on radiology; histology for CD1a/CD207/S-100 confirms the diagnosis and guides management, including smoking cessation, surveillance, and potential targeted therapies in refractory cases. This panel is essential for diagnostic confirmation in ambiguous clinical-pathological scenarios.

Transmission Electron Microscopy (TEM) image of an epidermal Langerhans cell illustrating Birbeck granules. Birbeck granules are zipper‑like, pentalaminar tubules with a dilated terminus that yields a tennis‑racket appearance; their canonical morphology is highly specific for Langerhans cells. In this specimen, the granules measure approximately 200–400 nanometers in length and about 33 nanometers in width, with a characteristic periodic, curvilinear lattice within the tubule walls. The dilated end often contains structural proteins such as langerin (CD207) and participates in antigen capture and processing. TEM historically served as a gold standard for diagnosing Langerhans cell histiocytosis (LCH) by demonstrating these ultrastructural features; however, modern diagnostic practice relies more on immunohistochemical markers (CD1a and CD207) and molecular tests, making TEM less commonly used. The surrounding cytoplasm shows abundant organelles consistent with active endocytic dendritic cells; cells may exhibit vesicular inclusions and moderate cytoplasmic granularity. This image highlights ultrastructural detail essential for educational purposes and differential diagnosis, particularly in ambiguous cases where immunophenotype is equivocal. Clinically relevant scenarios include suspected LCH in pediatric or adult patients, evaluating skin, bone, or organ involvement, and correlating ultrastructural findings with histology and flow immunophenotyping to confirm diagnosis and guide therapy planning. This image is valuable for teaching.