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2013 — January Case of the Month

Posted January 9, 2013

CLINICAL SUMMARY: Retroperitoneum  

CAP Foundation Online Case of the Month

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

A 44-year-old woman presented with abdominal pain and was discovered to have a retroperitoneal/pelvic mass which was resected, along with several lymph nodes. The retroperitoneal mass measured 8.0 x 3.5 x 3.0 cm and had a hemorrhagic cut surface. The lymph nodes were enlarged and the cut surface had a similar appearance to the pelvic mass. A hysterectomy and bilateral salpingo-oophorectomy was performed at the same time which was essentially unremarkable except for adenomyosis. Immunohistochemical stains performed on the retroperitoneal mass demonstrated actin (+), HMB-45 (+) and ER (+).

Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2010, case 1, and is a lymphangioleiomyomatosis.

Criteria for Diagnosis and Comments:
Lymphangioleiomyomatosis (or lymphangiomyomatosis) (LAM) occurs almost exclusively in reproductive age women and consists of a proliferation of immature myoid cells which are currently thought to derive from perivascular epitheliod cells (PEC). LAM may involve the lungs and axial thoraco-abdominal lymphatic system including both lymph nodes and the thoracic duct. Supraclavicular and inguinal nodes may rarely be involved. In most cases, the pulmonary manifestations dominate but LAM may occasionally present exclusively in the abdomen. Abdominal LAM may mimic ovarian carcinoma radiographically and patients may present with pain, often due to hemorrhage. LAM may occur in association with tuberous sclerosis (TS) or in isolation (sporadic LAM), although in either form the LAM cells may be associated with mutations of the TS genes, TSC-1 or TSC-2. Whether LAM is sporadic or associated with TS, the histologic appearance is the same but lymph node involvement is more frequent in patients without TS. In all locations, the cellular proliferation of LAM is characterized by short spindled cells with a slightly epithelioid appearance. The cells are usually arranged in short fascicles. In the retroperitoneum and lymph nodes, the fascicles are often adjacent to endothelial lined spaces, while in the lung cystic spaces are often present. Mitotic activity is absent. The cells are positive for actin and other smooth muscle markers such as myosin. Reflecting their probable derivation from PEC’s, the cells also express HMB-45. Most cases will also express ER and PR. There is debate regarding whether LAM represents a neoplastic or hamartomatous process, although analysis of recurrent LAM in patients who received lung transplantation suggests the former. While some patients respond to hormonal manipulation, an optimal treatment remains elusive. Improved understanding of the molecular pathogenesis of the disease has identified several promising markers for potential targeted therapy. While beyond the scope of the critique, the interested reader is referred to expert reviews on the molecular pathogenesis of this disease.

In the abdomen, the differential diagnosis of LAM includes primarily smooth muscle tumors as well as vascular tumors and vascular transformation of lymph nodes. Leiomyoma and peritoneal leiomyomatosis are generally characterized by bland proliferations of smooth muscle of variable cellularity. The smooth muscle cells in these lesions are typically much more elongate than the short spindle/epithelioid cells of LAM and have more abundant eosinophilic cytoplasm. While positive for smooth muscle markers, these lesions lack expression of HMB-45 which should easily separate them from LAM. Leiomyosarcoma is similarly negative for HMB-45, and the mitotic activity seen in these tumors should not be present in LAM.

Vascular lesions may have overlapping morphologic features with LAM, particularly those with a cellular component such as spindle cell hemangioma or Kaposi sarcoma (KS). The former should not be confused with LAM as it occurs almost exclusively in the distal extremities, but KS may involve lymph nodes or viscera and may be entertained in the differential. KS is associated with human herpes virus 8 (HHV-8) and is characterized by spindle cells associated with slit like spaces rather than the larger, endothelial-lined spaces encountered in abdominal/lymph node involvement by LAM. Hyaline globules and extravasated red cells may also be observed in KS. LAM cells are negative for the endothelial markers which are positive in KS, and KS is negative for HMB-45.

Vascular transformation of lymph nodes occurs secondarily to lymphatic or venous obstruction. It is characterized by capillary sized blood vessels involving the sinuses. Usually the vascular nature of the process is apparent but in extreme examples closely packed vessels may impart a cellular appearance. Typically the lymph node architecture is preserved, in contrast to LAM, and the vascular nature of the process may be appreciated toward the periphery of the node. In difficult cases, positive endothelial markers and absent staining for HMB-45 in vascular transformation of lymph nodes should distinguish these two processes.

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 lesion is characterized by positive staining with smooth muscle markers and HMB-45? A. Kaposi sarcoma
B. Leiomyosarcoma
C. Lymphangioleiomyomatosis
D. Peritoneal leiomyomatosis
E. Vascular transformation of sinuses (lymph node)
2. Which lesion is characterized by mutations of the tuberous sclerosis genes, TSC-1 or TSC-2? A. Kaposi sarcoma
B. Leiomyosarcoma
C. Lymphangioleiomyomatosis
D. Peritoneal leiomyomatosis
E. Vascular transformation of sinuses (lymph node)
3. Which lesion may involve the lymph nodes or viscera, is associated with HHV-8, is positive for endothelial markers and is negative for HMB-45? A. Kaposi sarcoma
B. Leiomyosarcoma
C. Lymphangioleiomyomatosis
D. Peritoneal leiomyomatosis
E. Vascular transformation of sinuses (lymph node)

References

  1. Juvet SC, McCormack FX, Kwiatkowski DJ, Downey GP. Molecular pathogenesis of lymphangioleiomyomatosis: lessons learned from orphans. Am J Respir Cell Mol Biol. 2007 Apr;36(4):398-408.
  2. Krymskaya VP. Smooth muscle-like cells in pulmonary lymphangioleiomyomatosis. Proc Am Thorac Soc. 2008 Jan 1;5(1):119-126.
  3. Krymskaya VP. Tumour suppressors hamartin and tuberin: intracellular signalling. Cell Signal. 2003 Aug;15(8):729-739.
  4. McCormack FX. Lymphangioleiomyomatosis: a clinical update. Chest. 2008Feb;133(2):507-516.
  5. Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors, 4th Ed. Mosby Press. St. Louis. 2001.

Author:
2010
Mary Beth Beasley, MD
Surgical Pathology Committee
Mount Sinai Medical Center
New York, NY