Just Getting Old?
Pathlet 007
Ryan Good '15
with the pathology team

These pathlets are edutainment. This site collects no information about visitors, and cannot substitute for your own doctor's care. There are many questions without clear right-or-wrong answers.


Louise de Ham
Portrait of an Old Woman
A 69 y/o, Caucasian, female, sought medical care for lower back pain about six months ago. She said that she was moving boxes around in the attic, it was late in the day, and she went to a local quick care clinic because it was after normal office hours. Her insurance would not cover the emergency room. The doc poked, prodded, and wrote a script for metaxalone 800 mg PO tid. The physician told her to use a warm, not hot, water bottle to the area as needed. If the symptoms do not resolve in a week, follow up with her primary care physician.

Harriet, being the tough old “gal” she was, finished off the medication and put up with the more than occasional aches and pains in her back, saying to herself “it’s just old age, and I am a spring chicken, so let’s get on with life”. She did not pay any attention to the occasional fevers she had been having but the fullness in her left side made her wonder. Then four days ago, she was showering to get ready for her date, with Mr. Right and noticed a couple lumps in the area of her right groin. At last she thinks, I must have a low-grade infection, so the next day (after an exhausting night) she makes an appointment to see you, her primary care physician.

You perform a complete history and physical examination. Your findings are positive for the following: A vague history of fever, but no weight loss or night sweats. Never a smoker, no alcohol, no breast masses, no occupational exposures, no pets, no foreign travel, no outdoor adventures, no weird diet, never any needle drugs. Mr. Right is clean-living so far as she knows. Physical exam findings include an enlarged spleen, palpable bi-lateral inguinal and left axillary adenopathy.

At this point, which of the following are you considering?

Berylliosis
Cat scratch fever
Cytomegalovirus
Disseminated carcinoma
Glanders
HIV infection
Hodgkin's disase
Infectious mononucleosis
Lupus
Kikuchi-Fujimoto
Non-Hodgkin's lymphoma
Sarcoidosis
Syphilis
Toxoplasmosis
Tuberculosis
Whipple's

You're probably thinking of non-Hodgkin's lymphoma, with sarcoidosis second and perhaps Hodgkin's third. The others seem a little far-fetched especially with the pertinent negatives.

What would you like to get next?

Angiotensin converting enzyme      
Anti-nuclear antibodies      
C-Reactive protein      
Chemical profile      
Chest x-ray      
CMV titers      
Complete blood count      
CT scan chest & abdomen      
HIV      
Mono-Spot      
Rheumatoid factor      
Serum beryllium      
Serum Whipple PCR      
Syphilis serology      
TB skin test / anergy panel      
Urinalysis      
Weil-Felix      

Immediately you call Harriet, have her come into the office, and discuss the situation with her. You both agree she needs a biopsy. You call the local surgeon Dr. Cutright, and schedule an appointment as soon as possible.

Dr. Cutright takes an inguinal lymph node.

The pathologist receives a specimen labeled inguinal biopsy “suspect lymphoma”; it consists of a 5.0 X 4.3 X 2.5 cm aggregate of yellow fibrofatty tissue with several enlarged lymph nodes ranging in size from 1.5 X 1.3 X 1.0 cm to 0.8 cm in diameter. The lymph nodes are encapsulated, gray-tan and on cut section vary from gray white and fleshy to dark purple in color. They are firm and rubbery.

The pathologist takes a slice of the gray white fish flesh area and submits it in RPMI held for flow cytometry, and sent for cytogenetics. A touch preparation is made for possible FISH (fluorescent in-situ hybridization).

Try your hand at reading these H&E's. All the tumor looked like this.

   

No pathology
Cat-scratch or some other bacterium
Follicular hyperplasia
Follicular lymphoma
Hodgkin's disease
Kikuchi-Fujimoto
Infectious mononucleosis
Sarcoidosis
Tuberculosis
Whipple's

You are so smart. What are you going to do now?

Count centroblasts / hpf      
FISH for t(14:18)      
Flow cytometry      
Stain for ALK      
Stain for BCL2      
Stain for BCL6      
Stain for CD10      
Stain for CD20      
Stain for CD21      
Stain for CD23      
Stain for CD30      
Stain for CD5      
Stain for Cyclin D1      

Once you are done, what is your diagnosis?

Anaplastic T-cell lymphoma
Chronic lymphocytic leukemia
Follicular lymphoma, grade 1
Follicular lymphoma, grade 2
Follicular lymphoma, grade 3A
Follicular lymphoma, grade 3B
MALT-oma
Mantle cell lymphoma

FINAL DIAGNOSIS: FOLLICULAR LYMPHOMA, GRADE 2, FOLLICULAR PATTERN

The grade is established by counting centroblasts, in this case 6-15 per high power field in the tumor areas. The stains confirmed the diagnosis. The t(14:18) translocation is classic. Full cytogenetic workup revealed t(14;18)(q32;q21), +7 and loss of 1p.

To grade a follicular-type lymphoma, countthe centroblasts (big lymphocytes with cleaved nuclei) per high power field. 0-5 is grade 1. 6-15 is grade 2. Grades 1 and 2 are low-grade. >15 is grade 3, high-grade. If centrocytes are still present, it's grade 3A, which tends to be less aggressive. If it's solid sheets of centroblasts without centrocytes, it's grade 3B, more aggressive.

We also report the proportion that has the follocular growth pattern. "Follicular" is >75%. "Follicular and diffuse" is 25-75%. "Focally follicular" is <25%. "Diffuse" has no follicular growth.

Grade 2 follicular lymphomas tend to be indolent. Harriet wisely opted for no treatment, and went on to marry Mr. Right.

Whether the lymphoma caused the low back pain is probably moot, as this problem did not recur.


"Elderly Couple"
Painter Unknown


Ryan Good KCUMB '15

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