Xantho-what? Pyelo-who?

NEJM 2000;342:1572.

I came across an unusual specimen this weekend while grossing for our pathology lab. A 62 yo woman had a nonfunctioning right kidney that appeared to have a mass by imaging. Of course, in this age group, a renal mass is worrisome for renal cell carcinoma or other primary renal tumor. However, based on her workup and imaging, this was likely xanthogranulomatous pyelonephritis (XGP). Our frozen section when she had her nephrectomy confirmed the diagnosis. This disease can certainly simulate an invasive malignancy, as seen in the CT image for this post. Also seen is perforation of the renal capsule with extruded contents (read: pus) into retroperitoneal and subcutaneous spaces.

What is XGP, you may ask?

Xanthogranulomatous pyelonephritis is a fairly rare entity but serious. It is essentially a chronic infection of the renal parenchyma (pyelonephritis). Interestingly, it is quite destructive, often destroying the medulla and cortex. Histologically, the cardinal finding is lipid-laden macrophages (xanthoma cells). Also are abscesses and granulomas (tada! there's the story behind the name). As is shown by this case, the disorder more frequently affects women than men, usually in the 6th and 7th decades of life. [why is it so hard to think: "6th or 7th decade...that means age 50s and 60s". it doesn't make sense...] Since XGP essentially destroys the kidney it affects, bilateral disease is generally fatal.

So, my job as a pathologist is to ask "why". Why do women in their 60s get this? As is the case in medicine, the answer isn't entirely known but likely the disease process required long-term obstruction and infection. In many cases, immunosuppression is a prerequisite predisposing factor. In our case, the removed kidney had large, "staghorn" calculi in the renal pelvis (it's a pretty exciting day for a pathologist when staghorn calculi are part of the daily grind...). Proteus and E. coli are often cultured. For the budding pathologists out there, the main differential diagnoses may be renal cell carcinoma, leiomyosarcoma and malakoplakia. The spindle cell component of XGP may not display the usual macrophage-rich areas. Demonstrating spindle cell and epithelial components would suggest a renal cell carcinoma with sarcomatoid elements. CD68 positive lipid-laden macrophages suggest XGP. The PAS-positive "Michaelis-Gutmann" bodies in histiocytes (macrophages) are characteristic of malakoplakia. FYI, macrophages and histiocytes: the same thing? Pretty much. Histiocyte is the more general term (i.e. macrophages, dendritic cells, and Langerhans cells are types of histiocytes). Histiocyte literally means "tissue cell". Of course, we all know that tissues have many types of cells besides histiocytes.

So, yes, often the treatment of XGP is nephrectomy or partial nephrectomy. I imagine it would have been quite difficult for antibiotics to penetrate the kidney I was dissecting and kill all that bacteria that was oozing out(yuck).

Complicating Cirrhosis

NEJM 2008;358:2378-87.

A few weeks ago we had an autopsy on a patient with just about every complication of cirrhosis one can have: severe portal hypertension requiring TIPS (transjugular intrahepatic portosystemic shunt) placement in the portal vein, esophageal varices necessitating banding and cautery, hepatic encephalopathy, and coagulopathy related to impairment of hepatic synthetic function. She would be a great case study for medical students learning about cirrhosis. Based on the autopsy findings, we think she developed cirrhosis from chronic hepatitis C infection and chronic alcoholism, two of the most usual suspects in the etiology of cirrhosis. One complication that was not suspected clinically was hepatopulmonary syndrome (HPS). This and hepatorenal syndrome are two entities that have been explored more recently in the medical literature.

The New England Journal has a decent review article on HPS that I stumbled across today in researching complications of cirrhosis. I thought it had a good image of the pathogenesis of hypoxemia in HPS. In any acute or chronic liver disease (usually with portal hypertension), pulmonary capillaries may be dilated with nonuniform flow and potential right-to-left capillary shunts. What results is a ventilation-perfusion mismatch and restricted diffusion of oxygen into the dilated capillaries. The efferent blood flow from the normal alveoli mixes with poorly oxygenated blood from those alveoli with dilated capillaries (potentially mixing with an intrapulmonary shunt) to give blood that lacks the usual oxygen concentration (hypoxemia). This can then result in inadequate supply to tissues and organs, rendering them hypoxic (hypoxia) [an aside: I often get hypoxemia and hypoxia confused...typing out the differences helps unmuddle this issue].

First Post

NEJM 2008;359:2707-18.

Exciting. My first post. Oh, what to write about?

Well, one of things I want to get out of this blog is putting down on "paper" some of the interesting lessons to be learned from the New England Journal of Medicine (NEJM). I feel that this periodical is so valuable for learning, whether it be clinical- (Pathology, Internal Medicine, Surgery, Pediatrics) or research-based. Since my medical school days I've actually felt excited (read: I'm a geek) when the newest issues are published online, each Wednesday. I usually turn first to the Case Record of the week where they present, in a clinicopathological correlation (CPC)-type approach, the latest interesting case from their hospital's experience. It gives the reader a chance to come up with her own differential diagnosis based on the history, presenting lab findings, and imaging studies. Then, experts who managed the case run through it with their personal approach, citing important studies and algorithms to approaching similar complaints. For instance, this week is a case of a 51-year-old woman who had anemia and MASSIVE splenomegaly (2.4 kg) [for those of you not acquainted with the usual size of spleens, this is extra super-sized - much bigger than even the liver should be in this sized patient. The usual spleen weighs somewhere around 100-150 gm]. Anyway, there are only a few conditions that result in spleens this big, including the condition that eventually is found to be afflicting this patient. SPOILER ALERT: in the event you haven't seen this case yet, surf away now.

The workup reveals an obvious hematolymphoid process at work, and a bone marrow biopsy is done. Based on the nodular lymphoid bone marrow aggregates and sinusoidal involvement, the immunophenotype (CD19+, CD5/23/10/103-), and histologic appearance in the spleen, the diagnosis was a splenic marginal zone B-cell lymphoma. A counterpart in younger men that also involves the liver (and is of course quite rare) is hepatosplenic gamma delta T-cell lymphoma. Of course, the cell of origin is different but the massive organomegaly is characteristic of both and neither have pronounced peripheral lymphadenopathy. Additional lessons to take away from the case include the workup of hemolytic anemia (Coombs-negative hemolytic anemias do exist) and that Hepatitis C infection is associated with this type of lymphoma. Also, CD103 is a immunomarker that is usually positive in hairy cell leukemia and is variably positive in splenic marginal zone lymphomas.

So, that's what I usually look at first on Wednesdays...looking forward to next week!