Pathology Image Of the Month: Rapidly Progressive Hemorrhagic Cellulitis of Bilateral Lower Extremities with Subsequent Septic Shock and Death.

A 51-year-old man presented to a community based emergency department with bilateral lower extremity swelling that began four days prior and that had evolved into recent blister formation on the left lower extremity. Medical history was significant only for hypertension and a recent self-described episode of "food poisoning" five days earlier characterized by diarrhea, nausea, and vomiting that quickly resolved. Physical exam revealed marked bilateral lower extremity edema and an ecchymotic rash below the knee. In addition to the rash, there were large flaccid bullae on the left leg, mostly intact but some notable for draining of scanty serosanguinous fluid. The patient was tachycardic with a rate of 114 bpm and initial labs showed thrombocytopenia (platelets 56 x 103/uL [140-440 x 103/uL]), hypoglycemia (15mg/dl [70-105mg/dl]), an elevated creatinine (2.7mg/dL [0.7- 1.25mg/dL]), and aspartate aminotransferase (AST 156U/L [5- 34U/L]). Two sets of blood cultures were drawn, broad spectrum antibiotics including doxycycline were empirically initiated and then he was subsequently transported to a tertiary care hospital for escalation of care. Within hours of presentation to the tertiary care facility, the rash appeared progressively hemorrhagic and bullous, lactic acidosis and coagulopathy developed and hemodynamic instability and septic shock necessitated endotracheal intubation and vasopressors. He was taken to the operating room for skin debridement but was emergently converted to bilateral above the knee lower extremity amputations due to the extent of the soft tissue necrosis. The patient remained intubated and in critical condition following surgery and the ecchymotic rash reappeared at the amputation sites. A newly developed ecchymotic rash with bullae formation was noted on the right upper extremity forearm. At that time, the clinicians were notified that four out of four blood culture bottles from admission were rapidly growing a microorganism. The family elected for withdrawal of care, and the patient died approximately 72 hours following presentation. A full and unrestricted autopsy was authorized by the Coroner's Office.

Pathology Image Of The Month: Recurrent Urinary Tract Infections In a 48-year-Old Female Hyperintensities in the Globus Pallidi.

A 48-year-old female presented to her physician complaining of intermittent lower abdominal pain radiating to the right lower back. At the time of presentation, she was afebrile and denied any urinary symptoms such as dysuria, frequency or urgency. Physical exam was unremarkable, other than obesity, and her abdominal exam was noncontributory. Medical history, however, was notable for recurrent, Proteus mirabilis culture-proven urinary tract infections requiring antibiotic treatment for the prior three years along with hypertension, uterine fibroids post hysterectomy, diabetes and asthma. Complete blood count was within normal limits, and urine dipstick showed 1+ blood, 1+ protein and 2+ leukocytes. Full renal function labs, urine cytology, radioisotope renography and abdominopelvic CT scanning with contrast were all ordered and a laparoscopic right nephrectomy was recommended based on the results. The bisected right kidney is shown below in Figure 1. She was discharged home on post-operative day one and her follow up urology appointments indicate resolution of both her urinary tract infections and her abdominal pain.

PATHOLOGY IMAGE OF THE MONTH: Sudden Cardiac Death Caused by an Uncommon Disease.

A 57-year-old female, found dead lying supine in bed, was transferred to the autopsy service for an unrestricted autopsy to be performed under the authorization by the coroner. Medical history was unknown. At the time of autopsy, an implantable cardioverter-defibrillator (ICD) was identified in the subcutaneous tissues of the left subclavicular chest, with distal leads terminating in a small amount of fibrous tissue within the right auricular appendage and along the medial wall of the right ventricle. The heart was enlarged at 430gm (312 ±78) and cross sections were notable for left ventricular hypertrophy at 1.9cm (1.0-1.5cm) and for dilatation of the right ventricular chamber on initial apical cross section. All cross sections, from cardiac apex to subvalvular base, showed broad patches of white-yellow myocardial discoloration, without obvious hemorrhage, along the free wall of the left ventricle, the free wall of the right ventricle, and within the anterior interventricular septum (Figure 1). Additional notable findings at autopsy included a vena caval filter devoid of thromboembolic material, a patent foramen ovale (0.7cm) and microscopic plexogenic arteriopathy, low grade, consistent with pulmonary hypertension within the intrapulmonary vasculature. Histology from the discolored patches of myocardium is seen in Figure 2. Special stains for microorgansims (periodic acid-Schiff, Gomori methanamine silver, and Fite) were all negative.

Pathology Image of the Month:Cough and Shortness of Breath in a Noncompliant Patient with HIV/AIDS.

A 37- year-old man with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) was admitted to the intensive care unit following a four month history of progressive shortness of breath, productive cough, and flu-like symptoms. His HIV/AIDS was diagnosed at the age of 19 (CD4 count =15; viral load = 294,436 copies/ mL) and was complicated by hemodialysis-dependent, HIV-associated nephropathy, prior Pneumocystis pneumonia and known noncompliance with prescribed antiretroviral therapy. Chest film at admission was interpreted as diffuse bilateral interstitial and airspace opacities with a right sided layering density representative of laminar pleural effusion. Bacterial blood cultures were subsequently negative. A bronchoalveolar lavage was performed and an image from the cytologic cell block is seen above in Figure 1. The patient's respiratory status continued to deteriorate and he was converted to comfort care. Following death, an unlimited autopsy examination was requested by the family and authorized by the coroner. At autopsy, additional gross pathologic findings included 350ml of chylous appearing pleural fluid and serous ascites (700ml). Histopathology revealed intra-alveolar acute fibrinopurulent exudate, chronic pericarditis and end-stage nephropathy. Similar cells to those shown above in Figure 1 were identified in lung epithelium and in pancreatic acinar cells. Special stain for Pneumocystis was negative.

Pathology Image of the Month: Prolonged Fever in a Traveler.

A 23 year old Russian male cargo ship crew member arrived in the port of New Orleans after a one month voyage originating in central Africa. During the month at sea, he developed fever up to 103 degrees Fahrenheit which was unsuccessfully managed with the antipyretic, dipyrone. He subsequently developed back and stomach pain, along with diarrhea. Upon the ship's arrival to New Orleans, he was transported to a local hospital where his axillary temperature was 104 degrees Fahrenheit. He was unresponsive, tachycardic and tachypneic with a plasma bicarbonate of 16mmol/L (24-32mmol/L).

Pathology image of the month: death in a young adult with sickle cell disease.

A 27-year-old African-American female with known sickle cell disease was admitted for sickle cell crisis and presumed sepsis. The patient's past medical history was complicated by multiple sickle cell-related complications, including seizures and multiple prior blood transfusions. Her hospital course included Staphylococcus epidermidis bacteremia, for which broad spectrum antibiotics were prescribed. On hospital day nine, the patient was found unresponsive and declared dead after unsuccessful efforts at resuscitation. An unlimited autopsy examination was conducted under authorization of the coroner. Findings included numerous pathologic features ascribed to sickle cell disease, including systemic siderosis and splenic atrophy [weight 10 gm (140±78)], fibrosis, and Gamna Gandy nodules. Additional autopsy findings included cardiomegaly with a heart weight of 450 gm (312±78), right atrial and right ventricular chamber dilatation, and hepatomegaly with a liver weight of 2650 gm (1475±362). The image below demonstrates microscopic examination of the lung parenchyma.

Pathology case of the month. Altered mental status, alcohol abuse, and hyperammonemia. DIAGNOSIS: Mallory-Denk bodies (a.k.a. Mallory's hyaline)­seen most commonly in alcoholic liver disease.

A 74-year-old woman with a past medical history of diabetes, hypertension, and alcohol abuse was brought to the emergency department and subsequently admitted to the intensive care unit with an altered mental status and weakness. Laboratories revealed acute renal failure (BUN 15 mg/dL, creatinine 2.5 mg/dL), elevated serum transaminase (AST of 83 IU/L), hyperammonemia (187 ug/dL), and marked normocytic anemia requiring transfusion of three units of packed red cells (hemoglobin 4.3 g/dL; hematocrit 13.1%). Blood ethanol level at the time of admission was less than 5 mg/dL, and full urine toxicology was negative. Alcohol abuse was reported to consist of, on average, "one pint of gin per day." Her hospital course was nine days and included complete inotropic blood pressure support and intubation. On the ninth day, she was declared dead, and authorization for an unrestricted autopsy was granted by the coroner. At autopsy, two liters of serous ascitic fluid was drained from the peritoneal cavity, and non-ruptured, distended varices were identified at the gastroesophageal junction. Additional findings included changes compatible with hypertensive cardiovascular disease, including hypertrophy of the interventricular cardiac septum and glomerulosclerosis along with renal atrophy. The liver weighed 1,300 grams (normal 1,475 gm±362) and was markedly discolored yellow-tan. Its parenchyma was more firm than usual. Representative microscopic sections from the decedent's liver are shown in the image below.

Pathology case of the month: sudden unexplained death in a young adult with known alcohol abuse.

A 35-year-old, recently deceased woman with a medical history known only to include Hepatitis C and alcohol abuse was transferred to the autopsy service for an unrestricted autopsy under coroner authorization following a sudden unexplained death. External examination revealed marked scleral icterus and cutaneous jaundice. Internal examination was remarkable for 3 liters of ascitic fluid and established cirrhosis with a micronodular pattern (nodules all <0.3 cm in diameter). Numerous, small, firm vegetations were identified along the edges of the tricuspid, mitral, and aortic valves. There was no obvious necrosis or tissue destruction seen grossly. Zones of prominent myocardial discoloration and hemorrhage were seen in all regions (anterior, lateral, and posterior) of the left ventricular myocardium, as well as within the interventricular septal myocardium. Multiple punctate lesions, up to 2 cm in diameter with a greenish hue and associated with tissue necrosis were seen overlying the cerebral cortex, as well as within the intracerebral parenchyma. Tissues were fixed in formalin for subsequent microscopic examination, and representative images from the aortic valve, and from the cerebral cortex, are seen below.

Pathology Image of the Month: Black Thyroid.

A 54-year-old Caucasian male had a witnessed collapse on the street. He was transported to the emergency department and subsequently pronounced dead. An unlimited autopsy examination was conducted under authorization of the coroner. Medical record review later revealed that the decedent had a history of alcohol abuse, chronic obstructive pulmonary disease, congestive heart failure, and chronic osteomyelitis treated by minocycline 100 mg twice daily. Autopsy revealed the cause of death to be ruptured gastroesophageal varices with nearly one liter of recent hemorrhage in the stomach and gastrointestinal tract. Other findings compatible with a history of alcoholism included hepatosplenomegaly, hepatic steatosis, and early bridging fibrosis. The decedent's thyroid was multinodular and enlarged at 50 gm. The thyroid gland, in its entirety, is shown below with serial sections made longitudinally through the gland capsule to reveal the underlying parenchyma.

Pathology image of the month. Black esophagus detected at autopsy in a patient with abdominal pain and bloody diarrhea. DIAGNOSIS: Acute esophageal necrosis, ischemic and pseudomembranous colitis.

A 73-year-old African-American male was transported to the emergency department due to what emergency personnel described as "coffee ground emesis." He was pronounced dead shortly after arrival. An unlimited autopsy examination was conducted under authorization of the coroner's office. Medical record review revealed that the decedent had been discharged from the hospital just one day prior to his death following a three-day admission for abdominal pain, bloody diarrhea, and a 22-lb unintentional weight loss. Medical history documented hypertension, chronic obstructive lung disease, and a 57-pack-year smoking history. Alcohol abuse was also endorsed, but cessation of use was reported six months prior. During that admit, he was treated for volume-depletion, a urinary tract infection, and suspected infective colitis with antibiotics. Symptoms had resolved on hospital day three, and the patient was discharged home with a two-week course of ciprofloxacin and metronidazole and a follow-up colonoscopy appointment in one month. At the time of autopsy, the decedent was described as cachectic. Figure 1a shows the decedent's esophagus, opened longitudinally. Figure 1b shows the corresponding histology from the esophagus. Other findings documented at autopsy included ischemic bowel disease in the descending colon with patchy superimposed pseudomembranous colitis, emphysematous change, papillary renal cell carcinoma of the right kidney, microscopic prostatic adenocarcinoma, hepatic fibrosis, and intact hepatic hemangiomata.

PATHOLOGY IMAGE OF THE MONTH. Autopsy Findings in an Adult with Down Syndrome.

Emergency medical responders were activated to the home of a 59-year-old African-American male in distress and with known Down syndrome complicated by Alzheimer's disease. He was found to be unresponsive and subsequently became pulseless. Advanced cardiac life support protocols were initiated and continued for two hours in the emergency department. Due to family request, efforts were eventually ceased and the patient was declared dead. Full, unrestricted autopsy examination was conducted under the coroner's authorization. The cause of death was determined to be a pulmonary thromboembolus in the main pulmonary artery with extension into the bilateral pulmonary arteries. Additional external findings included alopecia universalis, penoscrotal hypospadias, ostium secundum type of atrial septal defect, right ventricular cardiac dilatation, diffuse cerebral atrophy, facial features compatible with Down syndrome, and generalized patches of skin depigmentation over the hands as seen in Figure 1 but also over the feet, lips, areola, and trunk. Microscopic findings included features of pulmonary hypertension. A microscopic image from a section of the thyroid is seen in Figure 2.

Splenic nodules at autopsy.

Gamna-Gandy bodies (GGBs), also known as hemosiderotic nodules, were first described in 1921 in association with sickle cell disease. Since then, they have been documented to occur in association with other pathological processes such as hemolytic anemia, congestive splenomegaly, hereditary hemochromatosis; and acquired hemosiderosis. Despite a uniquely characteristic microscopic appearance that is easily recognized by routine histopathologic examination, the precise significance of GGBs remains unknown. As such, documentation of GGBs in patients either by pathology or radiology should herald the presence of a systemic disorder such as sickle cell anemia or hemochromatosis wherein portal hypertension and/or congestive splenomegaly are present. In this article, we briefly present two autopsy cases from two patients with distinctly different clinical presentations wherein classic Gamna-Gandy bodies are illustrated on routine histopathologic examination.

Left ventricular noncompaction cardiomyopathy.

Isolated Left Ventricular Non Compaction Cardiomyopathy (LVNCC) is a rare genetic cardiomyopathy characterized by a thickened left ventricle with two distinct layers - an inner noncompacted (spongy) layer and an outer compact (dense) layer. The spongy layer is composed of deep intertrabecular recesses. Familial and sporadic forms are known to exist and there is significant genetic heterogeneity among the inherited forms. Symptoms vary and range from asymptomatic to severe heart failure and sudden death. The clinical diagnosis of LVNCC can be challenging partly because there is currently no consensus for diagnostic criteria. As such, many affected individuals are, inopportunely, first diagnosed at post-mortem examination.

Positive newborn screen in a normal infant of a mother with asymptomatic very long-chain Acyl-CoA dehydrogenase deficiency.

A neonate with elevated tetradecenoylcarnitine (C14:1) on the newborn screen was evaluated for possible very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and found to be a carrier. However, his symptom-free mother was subsequently diagnosed with VLCADD. This documents maternal VLCADD causing a positive newborn screening result in an offspring.

Histopathological findings in fatal novel H1N1: an autopsy case series from September-November 2009 in New Orleans, Louisiana.

Autopsy findings are presented on six patients in the greater New Orleans area with confirmed novel H1N1 in New Orleans, Louisiana, between the months of September to November 2009. Each case was reviewed for antemortem clinical data as well as pre-existing comorbidities. Results from postmortem gross, histological and bacteriologic analyses are detailed and support the assertion that pathologic findings associated with novel H1N1 are similar to those attributed to previous pandemics, though the rate of bacterial super-infection is variable and may depend on the analytical method of microbiologic testing. The current case series is also remarkable for the associated rate of pulmonary thromboemboli and acute renal failure as potential clinical associations with the current pandemic.

Paternal balanced reciprocal translocation t(9;22)(q34.3;q11.2) resulting in an infant with features of the 9q subtelomere and the 22q11 deletion syndromes due to 3:1 meiotic segregation and tertiary monosomy.

The constitutional chromosomal reciprocal translocation (CRT) involving chromosomes 9 and 22 has been previously published in only five occasions. We report the sixth case of a balanced t(9;22) carrier who came to medical attention following the birth of his child with tertiary monosomy due to 3:1 meiotic segregation. This is only the second occurrence of paternal parent-of-origin to the t(9;22) CRT and is the first report of a t(9;22) undergoing 3:1 disjunction. It is also unique in its constellation of clinical features that overlap with two well-described cytogenetic microdeletion syndromes: the 9q subtelomeric and 22q11.2 deletion syndromes. With its uncommon breakpoint at chromosome 9q34, this case also emphasizes the added importance of array comparative genomic hybridization to analysis of offspring born to CRT carrier parents.

Adams-Oliver syndrome in siblings with central nervous system findings, epilepsy, and developmental delay: refining the features of a severe autosomal recessive variant.

Adams-Oliver syndrome (AOS) is a well-known rare syndrome of cutis aplasia in combination with limb defects. Recent reports have been published discussing the clinical variability and apparent genetic heterogeneity seen in some affected individuals and families with particular attention made to the possible existence of an autosomal recessive variant of AOS. We report on sisters as the ninth report of such an autosomal recessive-variant and review previously published similar sibships for observed comparisons relative to clinical features. Review of these cases is initially suggestive of an increased frequency of both central nervous system involvement as well as epilepsy in the autosomal recessive variant of AOS. Full case reports and a review of neurological involvement in the autosomal recessive AOS cases are presented.