METASTATIC ADENOCARCINOMAS OF UNKNOWN PRIMARY ORIGIN (MAUP)
Samuel P. Hammar
Diagnostic Specialties Laboratory, Bremerton, Washington

Introduction

A. Adenocarcinomas account for up to 60% of all metastatic tumors of unknown primary origin (MTUP)
B. As a general rule. adenocarcinomas are the most difficult MTUP to diagnose.

II. Histologic and histochemical features of MAUP

A. Some adenocarcinomas have fairly distinctive histologic features: e.g.. colonic adenocarcinoma. bronchioloalveolar cell carcinoma
B. Histologic stains such as mucin stains (PAS-d. mucicarmine) are occasionally helpful in diagnosing adenocarcinomas but are usually not specific enough to result in a definite diagnosis.

III. Relatively specific immunohistochemical tests to diagnose MAUP

A. Prostate-specific antigen (prostatic adenocarcinoma)
B. Thyroglobulin (thyroid carcinoma)
C. Surfactant proteins (pulmonary adenocarcinomas)
D. Estrogen and progesterone receptor proteins (breast carcinomas. mullerian carcinomas)
E. Thyroid transcription factor I (pulmonary adenocarcinoma)

IV. Relatively specific ultrastructural features to diagnose MAUP

A. Tubular myelin (surfactant-producing pulmonary adenocarcinoma)
B. Intranuclear surfactant apoprotein tubular inclusions (surfactant-producing pulmonary adenocarcinomas)
C. Clara cell granules (Clara cell adenocarcinomas)
D. Uniform short microvilli with filamentous cores and core rootlets (colonic adenocarcinomas and some pulmonary adenocarcinomas)
E. Langerhans cells (most frequently associated with non-mucinous bronchioloalveolar cell carcinomas)
F. Lipid droplets glycogen and cytoplasmic crystals (renal cell carcinoma)
G. Intracytoplasmic hyaline globules [?giant lysosomes] (pulmonary adenocarcinoma)

Tubular myelin in pulmonary adenocarcinoma	Intranuclear surfactant apoprotein tubular inclusions
Intranuclar tubular inclusions (higher magnification)	Birbeck granules in Langerhans cell

V. Immunohistochemical tests of uncertain specificity for diagnosing MAUP

A. Keratins 7, 20 and 19
B. Villin
C CEA
D. 5100 protein
E. CA 19-9, CA 125, BCA 225

VI. Ultrastructural features of uncertain specificity for diagnosing MAUP

A. Myelin figures
B. Microvilli
C. Glycogen and lipid
D. Endoplasmic reticulum

VII. Special situations

A. Well- to moderately-well differentiated epithelial mesothelioma versus well- to moderately-well differentiated pulmonary adenocarcinomas

1. TEM best single test to make absolute diagnosis
2. IHC helpful in most cases

B. Pseudomesotheliomatous adenocarcinoma versus pseudomesotheliomatous epithelial hemangioendothelioma versus well- to moderately-well differentiated epithelial mesothelioma

1. IHC profile very helpful if correct panel of tests is done
2. EM is usually diagnostic if examination performed by an experienced ultrastructural pathologist

C. Neuroendocrine neoplasms can show glandular and amphicrine differentiation

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