Interesting soft tissue case

Got an interesting case, wondering what everybody thinks.

core bxs of a large L medial thigh mass (with destructive involvement of left pubis ramus) in a guy in his late 20s. also has multiple bilateral pulmonary lesions. the small blue cells infiltrating skeletal muscle are lymphocytes and plasma cells.

shows vimentin and CD56 staining but negative for a whole host of markers:

CD99-, desmin-, pankeratin-, AE1/AE3-, EMA-, S100-, GFAP-, CD117-, PLAP-, inhibin-, CD31-, p63-, melanoma markers -, synapto and chromogranin-, MSA/HHF35-, OCT3/4-, SALL4-.

also was negative (in 100 cells) for EWS translocations based on breakapart FISH probes on paraffinized tissue.

Our expert consultation called it an undifferentiated round cell malignant neoplasm.

Any thoughts???
4X

10X



20X

40x

100x

Vimentin

SMA

CD56

CD99

CD45

A 21-year-old Female with Acute Liver Failure and Hemolytic Anemia

Had an interesting case this month that my Blood Bank team was involved with. I've changed some of the information to protect her privacy.

A 21-year-old female presented with a 5 week history of fatigue, anorexia, and mild jaundice. She was previously healthy with no past medical history, no medications, and no drug use. The initial workup showed a normochromic, normocytic anemia (Hgb 11.5) and increased liver function tests and was negative for infectious mononucleosis and viral hepatitis. Just a few days after this basic workup her course worsened and she became more severely jaundiced and developed dark urine and right upper quadrant pain. She was admitted to a referring institution and the workup showed the following:

Afebrile and vital signs stable
Scleral icterus, jaundice, splenomegaly, and RUQ pain on exam

WBC: 13.5 H
Hgb: 6.5 L
Plt: 178
Creatinine: 2.2 H

ALT: 13
AST: 147 H
Alk phos: 17 L
Tbili: 42.9 H
Dbili: 12.6 H

INR: 3.1 H
Albumin: 2.3 L

LDH: 659 H
Haptoglobin: undetectable L
Retic: 11.79 H
Direct antiglobulin: neg.
Blood type: O+, Ab screen neg.

ANA: within normal limits
Serum pregnancy test: neg.

Does anyone have a diagnosis? I'll post it in a week with follow up photos in a new post and/or comment.

A 30-year-old man with an intracranial parafalcine mass

We received an unusual case on our neuropathology service this week. The specimen was a 4 cm frontal, extra-axial mass that was dural-based, abutting the falx cerebri. MRI showed intense enhancement with surrounding vasogenic edema and a small dural tail. There was only mild mass effect and diffusion weighted imaging (DWI) showed no diffusion restriction. Cerebral arteriography showed a hypervascular lesion. Left middle meningeal artery embolization was performed preoperatively. At craniotomy the tumor was liquid and necrotic-appearing and the excised specimen was sent to us for pathological examination. The histological appearance is depicted below (click on photos to get higher resolution):

Glassy, eosinophilic cytoplasm with inclusions

Atypical cytology with some prominent nucleoli (occasional mitoses were also identified [~1-2 per 10 high-powered fields])

Focal areas of necrosis and hemorrhage

MIB-1 (Ki-67) immunostain showing a 15-20% proliferation rate.

Additionally, a vimentin immunostain showed strong diffuse cytoplasmic positivity and an EMA immunostain showed positive membrane staining. Cytokeratin immunostain was negative. How would you diagnose this case?

What to read?

Pathology is one of the study-heavy specialties, along with others like Radiology and Radiation Oncology. The benefit of a "normal", "predictable" workday is offset by all the reading you must do on the side, over the weekend and holidays, and when family thinks that you've finished the crazy studying routine set forth in the formative years. My choice for tonight is one of the main Pathology journals, as shown above: Archives of Pathology and Laboratory Medicine. It has a resident-friendly format with, in addition to original research articles, teaching cases and a differential diagnosis approach to certain findings after imaging or microscopic examination.

Medical school certainly doesn't prepare a student for any one specialty. Of course it can't. But, surgeons may start residency having only held retractors for 10-hour long surgeries. Family physician residents may not have done simple office procedures. Emergency med residents may never have placed defibrillator pads on a live patient.

In Pathology, most of my fellow residents and I feel particularly unprepared to begin residency in this specialty. Yes, we get histology and some basic pathology during the first and second years of medical school. Perhaps we saw an autopsy or two. But we certainly didn't learn how to formulate a report for cases that we now see. Or do an autopsy mostly by ourselves and know how to pay particular attention to certain areas of the body in order to pick up key findings. For example, there are special, non-routine ways to check for pneumothorax or air embolism, if those are suspected as a cause of death. If not suspected clinically it may not be tested for and thus, not uncovered.

For Surgery, Family Practice, Internal Medicine...you are expected to be a somewhat-functioning resident as you step into the physician shoes on day 1. Hence all the training in learning to interview patients, write History and Physicals, check and interpret lab test results, and present cases to fellow colleagues on rounds or over the phone.

As for us, the Pathology, Radiology, Radiation Oncology residents out there, we generally found our field of choice by doing a rotation during medical school in our respective fields. But these were usually "litmus test" rotations so that we assured ourselves of choosing something in which we have genuine interest so we can happily practice for the rest of our career. Maybe we pick up a few useful skills, but nothing on the order of super-practical.

I am not bitter about the lack of preparation for Pathology. However, I think important improvements could be made in the way basic pathophysiology can be taught and integrated with clinical learning. One solution is the clinicopathological case (CPC) based conferences. They are of particular interest and relevance, I believe. They are the same format as those published weekly by the New England Journal of Medicine. Our teaching institution has similar conferences, but just once per month. At the Dartmouth-Hitchcock Medical Center in New Hampshire, there were weekly CPC conferences (M&M conferences). I love these types of presentations - integrations of research, pathology, clinical cases, and quality improvement. My vote: more, please!

Reaching Back and Moving On

It's markedly difficult to engender a relationship with 1400+ pieces of paper - bound and covered, mind you - but I've spent more time with this treatise than I have with much of my family over the last several years. And I am close with them.

Just about every medical student trained in this country (and countless students in the rest of the world) is familiar with this textbook, "Big Robbins". I made it through the entire text during my second year of school, covering everything from the general principles of Pathology to specific disorders of every organ in the body. As a "basic", "introductory" text, it is quite complete - something I've appreciated this year as a new Pathology resident. As I build the foundations of expertise in Pathology, I find myself turning back to Robbins more often than not. I hoped that covering every word in medical school would prepare me for moving on to something more complex this year as I build upon basic knowledge. I can point to a few reasons why I'm going back to the building blocks I obtained over four years ago.

One is the speed at which medicine progresses with the volumes of literature published every month. The understanding of old diseases and discovery of new ones divide at alarming rates. If there were enough pathologists working on Robbins, it would be (or should be!) updated yearly to reflect the massive number of changes. The edition I read is soon to be two editions old. A dinosaur in modern medicine, it lacks discussion of the human genome project, for instance.

The other reason to go back is simply the sheer amount of knowledge I've...left behind...over the years. Reading, studying, and being examined on Robbins reading wasn't enough to let my mind retain nearly enough. Just like a full-length feature film, it takes more than one time through to memorize ALL the lines.

And of course, I actually enjoy reading Robbins. I did the first time I picked it up and hope to for many years to come. Potentially I'll be comfortable with most of the content in a few years so it will remain in my library as only a consultant. Don't worry, Robbins, it's safe to say you'll always have a place in my heart. No matter how much weight you gain with future editions.

I have a 3-month block of Surgical Pathology coming up, in which I'll be rotating through several different specialty areas of Surg Path, the biggest field of a typical Anatomic/Clinical Pathology training program. January is Genitourinary/Renal/Neuro, February is Gastrointestinal, and March is Endocrine/Pulmonary/Head&Neck. Many programs are moving to specialty rotations rather than doing General Pathology (all cases bunched together). I like it because I can assume a focused method of studying and examining cases, similar to the approach of traditional medical school curricula. There's really nothing like spending a full, cold Milwaukee winter night curled up by the fire, reading about all the types of infections the prepuce can develop. Thanks, Robbins!

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].