Baylor University Medical Center Proceedings

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Pathology Quiz

Daniel A. Savino (Pathology Editor)

To cite this article: Daniel A. Savino (Pathology Editor) (1993) Pathology Quiz, Baylor University
Medical Center Proceedings, 6:4, 23-25, DOI: 10.1080/08998280.1993.11929834

To link to this article: https://doi.org/10.1080/08998280.1993.11929834

Published online: 28 Jan 2018.

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 Pathology Quiz
Daniel avino. D. Pathology Editor
~1II~~iii~~l • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • •

Test your diagnostic skills by responding to the ques- ture-pain/pressure-vibration perception with preserva-
tions and comparing your answers to those provided. tion of deep tendon reflexes led to the diagnosis of
-Ed. leprosy in this patient.

CLINICAL SUMMARY
The patient was a 31-year-old woman from Pakistan
being evaluated at a Dallas-Fort Worth area hospital for
weakness of the hands and numbness of the upper and
lower extremities (worse distally) . There was no family
history of neurologic diseases . On physical examina-
tion, the significant findings included reduced strength
and muscle volume in all extremities and reduced per-
ception of temperature and pain distally. The deep ten-
don reflexes, vibration perception, and gait were normal.
Light and electron photomicrographs were taken of
transverse sections of a sural nerve biopsy specimen
sent to Baylor University Medical Center for pathologic
examination. Figure 1. Light photomicrograph showing a cross section of a
pe rip hera l ner ve with focal evi de nce of an infl amm ato ry
QUESTIONS mononuclear -ce ll infilt rate and a decreased number of thick.
o What is your diagnosis based on the clinicopathologic myelinated fibers (x 1200).
clues available?
@ What is the general classification of this disease?
e What are the main causes of peripheral neuropathy?
o What are the pathologic findings in these peripheral
neuropathies?

ANSWERS
o The light photomicrograph (Figure J) shows a cross
section of a peripheral nerve with focal evidence of an
inflammatory mononuclear-cell infiltrate and a decreased
number of thick, myelinated fibers . The electron pho-
tomicrograph (Figure 2) shows scattered cells with cy-
toplasmic vacuoles and occasional clusters of
electron-dense, rod-shaped structures suggestive of in- Figure 2. Electron photomicrograph showing scattered cells with
tracellular microorganisms. These findings and the cytoplasmic vacuoles and occasional clusters of electron-dense.
important clinical clues of "dissociation" of tempera- rod-shaped structures (x4560).
23
 24 BAYLOR UNIVERSITY MEDICAL CENTER PROCEEDINGS VOL. 6, NO.4

• Distributed worldwide, leprosy is the most common d. Amyloidosis; and

treatable neuropathy. Although Koch's postulates have e. Neuropathies caused by tumor invasion.
not been fulfilled completely (the etiologic organism 2. Chiefly axonal neuropathies-diseases that affect
has never been cultured in artificial media), there is mainly the neurons, their extensions, or both, in-
little doubt that leprosy is an infectious disease, albeit cluding
not readily contagious, caused by Mycobacterium leprae, a. Metabolic, toxic, and deficiency disorders (e.g.,
a 1-8 J.1 x 0.2-0.5 J.1 acid-fast bacillus first linked to the diabetes, uremia, chronic liver disease, porphyria,
disease in 1874. alcoholism, chemotherapy, heavy metal intoxica-
From a clinicopathologic standpoint, leprosy is clas- tion);
sified in four forms. Indeterminate leprosy is an infre- b. Neoplastic states (e.g., carcinomas or hemato-
quently diagnosed, indolent form that may resolve logic malignancies);
spontaneously or evolve into one of two polarized forms c. Dysglobulinemias (e.g., multiple myeloma or
(tuberculoid leprosy in patients with high immune re- cryoglobulinemia); and
sistance and lepromatous leprosy in patients with low d. Various other disorders (including tropical spas-
immune resistance) or an intermediate form between tic paraparesis due to HTLV-1 infections, chronic
those two (dimorphous or borderline leprosy). hypoxia, and polyneuropathy after prolonged re-
Patients with indeterminate leprosy present with a suscitation).
solitary, slightly hypopigmented skin lesion with slight 3. Chiefly demyelinating neuropathies-diseases result-
sensory reduction. Pathologically, the lesion shows in- ing in loss of myelin sheaths, including
conspicuous foci of chronic inflammation around skin a. Acquired demyelinating neuropathies (acute and
adnexa and nerves (the latter may contain few bacilli). subacute demyelination), either
Patients with tuberculoid leprosy present with a • Inflammatory (Guillain-Barre and variants: im-
limited number of well-localized, asymmetric skin le- mune-mediated neuropathy presenting as a se-
sions (usually located in those areas of the body with quel to or in the course of infections, vaccination,
the lowest temperature) as well as thickening of some surgery, pregnancy, immunosuppression, and can-
subcutaneous nerves (which are palpable). Biopsy speci- cer),
mens show well-formed granulomas involving the skin, • Dysglobulinemic (mainly IgM demyelinative
skin appendages, and cutaneous and subcutaneous polyneuropathy and polyneuropathy associated
nerves. Bacilli are scant and difficult to find in tissue with the POEMS [polyneuropathy, organomegaly,
sections. endocrinopathy, M protein, skin changes] syn-
In patients with lepromatous leprosy, there is he- drome), or
matogenous dissemination of bacilli which proliferate • Drug-induced (mainly the neuropathies caused
unchecked throughout the body. Biopsy specimens of by amiodarone and chloroquine); and
the skin lesions show accumulations of histiocytes with b. Hereditary demyelinating neuropathies, either
"foamy" cytoplasm (Virchow cells) containing innu- • Familial hypertrophic neuritides (Charcot-Marie-
merable bacilli; these encapsulated masses are termed Tooth disease is most common; Dejerine-Sottas
globi. The appearance of the globi is similar to that seen disease is exceptional; Refsum disease is very rare),
in some AIDS patients in which intracellular, atypical • Tomaculous neuropathy (from the Latin
mycobacteria accumulate within aggregates of histio- tomaculum sausage, because of the local thicken-
cytes. ing of myelin sheath; it usually is a familial recur-
In patients with dimorphous leprosy, a spectrum of rent compressive trunk neuropathy), or
findings is possible between the polar tuberculoid and • Neuropathy in leukodystrophy (mainly seen in
lepromatous varieties, depending on the patient's de- sulfatidosis, Krabbe's disease, and adreno-
gree of immune response. myeloneuropathy).

• Numerous possible causes of peripheral neuropathy 8 The three main constituents of the peripheral nerves
may be classified as follows: are 1) connective tissue structures, including blood ves-
1. Interstitial neuropathies-diseases affecting most sels, 2) neural cell extensions (axon or true nerve fi-
of the elements that make up the peripheral nerves, bers), and 3) myelin sheaths, which are formed by
including Schwarm cells. Regardless of etiology, all injuries to
a. Vasculitis; the peripheral nerves result in a limited number of
b. Leprosy; pathologic processes that can be grouped into three
c. Sarcoidosis; categories:
OCTOBER 1993 PATHOLOGY QUIZ 25

l. Interstitial (connective tissue) reactions the other. Thus, a great deal of caution is required when
• Nonspecific inflammation-usually presenting as interpreting the findings to decide whether axonal or
lyrnpho-plasmocytic perivascular aggregates; myelin sheath changes predominate.
commonly due to collagen vascular diseases Other than confirming the existence of a peripheral
• Vasculitis-the main forms encountered on biop- neuropathy, the finding of axonal changes contributes
sies of peripheral nerves are I) vasculitis of the little to the differential diagnosis; most toxic or meta-
polyarteritis nodosa group (in larger vessels) and bolic neuropathies result in axonal degeneration. This
2) leukocytoclastic vasculitis (in smaller vessels) also is true of any interstitial lesion that usually results
• Granulomatous inflammation-as in tuberculoid in axonal degeneration distal to the area of injury.
leprosy and sarcoidosis; the latter may cause ei- Alternatively, the finding of predominant myelin
ther multineuritis simplex (frequently involving sheath changes allows some degree of discrimination
facial nerves) or a symmetric distal polyneuropathy. between a number of acquired disorders (which cause
Interestingly, tuberculous neuritis has never been acute or subacute demyelination) and a group of less
reported. common, genetically determined diseases.
• Infiltration by microorganisms-the best example In cases of acute or subacute demyelinating dis-
is the lepromatous form of leprosy; however, the eases, teased-nerve preparations show individual fibers
most common form of leprosy seen as an unsus- that lack the myelin sheath, affecting one or more seg-
pected finding in a nerve biopsy is dimorphous ments between nodes of Ranvier. Remyelination is char-
leprosy (showing only a nonspecific mononuclear acterized by fibers showing one or more segments shorter
infiltrate and few microorganisms that are best than the rest.
seen by electron microscopy) Pathologic changes in the hereditary group of dis-
• Amyloid deposition----peripheral neuropathies sec- eases include:
ondary to amyloidosis usually are seen only in • In hypertrophic neuritides, the recurrent demyelina-
cases of I) hereditary amyloidosis, 2) so-called tion and remyelination result in a concentric prolif-
primary amyloidosis, or 3) amyloidosis associ- eration of Schwarm cells with formation of structures
ated with dysglobulinemia due to a malignant reminiscent of the cut surface of an onion bulb.
process • In tomaculous neuropathy, teased-nerve preparations
2. Axonal reactions show the typical sausage-like focal thickening due to
• Degeneration intussusception of the myelin sheaths beginning in a
• Regeneration paranodal region.
• Atrophy • The neuropathies of leukodystrophy are character-
• Hypertrophy (generally localized or segmental) ized by the presence of cytoplasmic inclusions (seen
3. Myelin sheath reactions with electron microscopy) in Schwann cells.
• Acute: Demyelination and remyelination
• Chronic: Onion-bulb formation Acknowledgment
Interstitial reactions can be diagnosed with light Grateful appreciation is extended to George Bridges for
microscopy. However, axonal and myelin changes (un- his assistance with the electron microscopy and photo-
less very advanced) require three approaches: I) special graphs.
stains on sections of snap-frozen nerve biopsy portions,
2) electron microscopy, and 3) teased-nerve prepara- General References
tions (obtained by meticulous "teasing" under a dissect- 1. Sabin TD, Swift TR: Leprosy, chap 84. In Dyck PJ, Thomas PK,
ing microscope of individual nerve fibers after treatment Lambert EH, et al, eds: Peripheral Neuropathy. 2nd ed, vol II.
of the biopsy specimen with osmium). In practice, purely Philadelphia, W. B. Saunders Co., 1990. p 1955.
2. Gherardi RK: Neuromuscular pathology, chapter 11. In Poirier J.
axonal or demyelinating neuropathies are seldom en-
Gray F, Escourolle R, eds: Manual ofBasic Neuropathology, 3rd
countered because of the close trophic relationship be- ed. Philadelphia. W. B. Saunders Co., 1990. pp 209-250.
tween axons and Schwarm cells; most conditions 3. Weller RO, Cerv6s-Navarro J: The Pathology of Peripheral
affecting one will result in some degree of damage to Nerves. London, Butterworth, 1977.