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2011 — December Case of the Month

Posted December 8, 2011

CLINICAL SUMMARY: Placenta  

CAP Foundation December 2011 Online Case of the Month

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After reading the summary, try answering the three related multiple-choice questions below.

A 35-year-old G3P1T1 presented at 18 weeks gestation with intrauterine fetal demise. Fragmented placental and fetal tissue measuring 12.0 cm in aggregate without gross abnormalities was received.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2008, Case 37, and is chronic villitis secondary to cytomegalovirus infection.

Criteria for Diagnosis and Comments:
The placental tissue is remarkable for multifocal chronic villitis composed of a lymphoplasmacytic and histiocytic infiltrate, villous stromal necrosis with associated acute inflammation, fibrosis, and calcifications. The presence of plasma cells and villous necrosis in the setting of fetal death is strongly suggestive of CMV infection and the characteristic inclusions are abundantly present in this case.

Chronic villitis is defined as the presence of chronic inflammatory cells, most commonly lymphocytes and plasma cells, present within terminal villi. Its presence may be associated with either viral infection (‘specific’ or infectious chronic villitis) or it may be idiopathic (‘non-specific’ or ‘of unknown etiology’). Infectious chronic villitis may be caused by a variety of different organisms, often grouped together under the acronym ‘TORCH’ standing for toxoplasmosis, other, rubella, cytomegalovirus and herpes simplex. The category of ‘other’ infectious agents associated with chronic villitis is large and includes HIV, varicella zoster and syphilis among others.

Cytomegalovirus (CMV) associated chronic villitis results in a histologically variable appearance ranging from minimal chronic inflammation to a severe chronic inflammatory infiltrate composed of lymphocytes, plasma cells and histiocytes. In severe cases, villous stromal necrosis with acute inflammation, villous fibrosis and calcifications are present. The characteristic intranuclear and cytoplasmic inclusions of CMV are more likely to be evident on histologic examination when chronic villitis is present in association with plasma cells in the villi, villous necrosis with acute inflammation and fetal death as in this case.

Herpes simplex infection (HSV) associated chronic villitis does not have a specific appearance and the typical ground glass viral inclusions are only rarely identified. The presence of giant cells is not specific and may be seen in both infectious and non-infectious chronic villitis.

Syphilis should be suspected whenever the triad of hypercellular villi, proliferative fetal vascular changes with vascular obliteration and ‘onion-skinning’ of vessels and acute or chronic villitis is present. In the absence of clinical findings, the presence of chronic villitis and hypercellular villi without the characteristic vascular changes is non-specific.

Toxoplasmosis results in the greatest fetal morbidity if infection occurs during the first trimester. Although there may be no associated inflammation, chronic villitis, which may sometimes be granulomatous, can be present. The characteristic cysts containing numerous organisms are only rarely found in the villi; the membranes and Wharton’s jelly are more common locations.

Chronic villitis of unknown etiology (non-infectious chronic villitis) represents the vast majority of chronic villitis, even in cases associated with fetal demise. Importantly, these cases are associated with a 20% recurrence risk for the patient. Although these cases may be associated with an as of yet undiscovered infectious agent, the finding that the intravillous and perivillous chronic inflammatory infiltrate is derived from maternal cells with a helper T cell predominance has led to the hypothesis that this process may be immune-mediated.

Supplementary Questions: For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question Diagnostic Set
1. Which entity represents the most common type of chronic villitis and is associated with a recurrence risk of up to 20%? A. Chronic villitis of unknown etiology
B. Chronic villitis secondary to cytomegalovirus infection
C. Chronic villitis secondary to herpes simplex infection
D. Chronic villitis secondary to syphilis
E. Chronic villitis secondary to Toxoplasma gondii infection
2. Which entity is characterized by the triad of hypercellular villi, proliferative fetal vascular changes with vascular obliteration and 'onion-skinning' of vessels and chronic villitis? A. Chronic villitis of unknown etiology
B. Chronic villitis secondary to cytomegalovirus infection
C. Chronic villitis secondary to herpes simplex infection
D. Chronic villitis secondary to syphilis
E. Chronic villitis secondary to Toxoplasma gondii infection
3. The presence of chronic villitis associated with plasma cells, villous necrosis and calcifications is most commonly associated with which entity? A. Chronic villitis of unknown etiology
B. Chronic villitis secondary to cytomegalovirus infection
C. Chronic villitis secondary to herpes simplex infection
D. Chronic villitis secondary to syphilis
E. Chronic villitis secondary to Toxoplasma gondii infection

References

  1. Labarrere CA, McIntyre JA, Faulk WP. Immunohistologic evidence that villitis in human normal term placentas is an immunologic lesion. Am J Obstet Gyn. 1990; 162:515-522.
  2. Redline RW, Abramowsky CR. Clinical and pathological aspects of recurrent villitis. Hum Pathol 1985; 16:727-731.
  3. Redline RW, Patterson P. Villitis of unknown etiology is associated with major infiltration of fetal tissue by maternal inflammatory cells. Am J Pathol. 1993; 143:473-479.
  4. Saunders E. Operative or induced delivery for maternal or fetal disorders: Diagnostic Gynecologic and Obstetric Pathology. In: Crum CP, Lee KR eds. Philadelphia, PA. 2006; 1097-1103.

Author:
2008
Marisa R. Nucci, MD, FCAP
Surgical Pathology Committee
Brigham and Women’s Hospital
Boston, MA