Michael T. Mazur

Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study

Eight cases of acute interstitial pneumonia were studied to define the clinical and pathologic features and to determine the relationship to chronic interstitial pneumonia. Clinically, this disease differs from the chronic interstitial pneumonias by a sudden onset and a rapid course. Five patients died of respiratory failure after 23 days to 2 months, and two died of other complications after 3½—6 months. An etiologic agent could not be identified in any case. The histologic hallmark was interstitial fibrosis and edema associated with type II pneumocyte hyperplasia. The fibrosis differed from that seen in the chronic interstitial pneumonias by extensive fibroblast proliferation and relatively little collagen deposition. Autoradiographic studies of tritiated thymidine (3H-TdR) uptake showed high labeling indices in interstitial cells and type II pneumocytes. Evidence of acute lung injury, including both endothelial and epithelial cell damage, was a prominent ultrastructural feature. These findings emphasize that acute interstitial pneumonia is a clinically and pathologically distinct form of interstitial pneumonia that should be separated from the group of chronic interstitial pneumonias.

Atypical polypoid adenomyomas of the endometrium.

Five unusual polypoid lesions of the endometrium which we term atypical polypoid adenomyomas are described; these growths occurred in premenopausal women. Each of the polyps was characterized by irregular atypical glands with squamous metaplasia and a cellular, smooth muscle mesenchyme, having a pattern to be distinguished from infiltrating adenocarcinoma or a malignant mixed müllerian tumor. Electron microscopy in one case confirmed the presence of a well-differentiated smooth muscle component. These lesions were focal and noninvasive. Two of the three patients who had hysterectomies had small residual lesions confined to the endometrium. Follow-up from 4 to 24 months showed no recurrence. One patient had a second D & C reported as normal; she subsequently became pregnant. The benign behavior of these unusual polyps suggests that atypical adenomyomas can be managed conservatively in the premenopausal woman without the necessity of a hysterectomy.

Proliferative serous tumors of the ovary. Histologic features and prognosis.

ABSTRACTIn reviewing all proliferative serous tumors of the ovary seen at Barnes Hospital from 1950 to 1974, we quantitated histologic characteristics and defined criteria for diagnosis in 55 borderline tumors, 13 well-differentiated cystadenocarcinomas, and 15 cystadenomas with unusual proliferative areas. This last type with focal proliferation behaved in a benign fashion and should be considered a variant of a simple cystadcnoma. Stromal invasion was the only histologic feature which consistently distinguished carcinomas from the borderline tumors. The presence in some borderline tumors of severe cellular atypia, marked epithelial disorganization, frequent mitoses, and cribriform glands in the stroma neither signified carcinoma nor indicated poor prognosis. No patient with a Stage I borderline lesion died of tumor. Although the mortality of patients with Stage IIb or Stage III borderline tumors is high, tumor-related deaths rarely occurred before 5 years, and three patients lived more than 10 years. Borderline serous tumors arc low-grade malignant neoplasms which differ from overt carcinomas in the excellent prognosis of Stage 1 lesions and in long survival even with widespread abdominal disease.

Metastatic Melanoma: The Spectrum of Ultrastructural Morphology

The fine structure of 26 metastatic melanomas, including 13 pigmented and 13 amelanotic tumors, as studied to define ultrastructural criteria for diagnosis. Several important features in addition to melanosome granules were identified. Dendritic cytoplasmic processes were seen in 25 of the 26 cases, cell clusters formed by concentric aggregates of several cells and their processes were present in 18, and microvilli were found on cell surfaces in all cases. The cytoplasm was complex, containing numerous mitochondria, Golgi systems, endoplasmic reticulum, nonspecific filaments, and microtubules. Nuclear morphology was variable. Basement membranes and cell junctions including desmosomes were often encountered, and some melanomas shared features with Schwann cells, including complex membrane interdigitations. All tumors contained melanosomes, although the classic forms were frequently difficult to identify and abnormal variant forms often predominated. Knowledge of the variant melanosome morphology and an understanding of the other fine structural features of malignant melanocytes can help identify those cases that lack classic premelanosome granules.

Histogenesis of morphologic variations in tumors of the uterine wall

&NA; We investigated seven uterine wall lesions, selected because of the presence of unexpected patterns or components, to determine their relationship to normal uterine constituents. These lesions included a bizarre leiomyoma, a palisading leiomyoma which resembled a schwannoma, two myxomas, irradiated myometrium, a plexiform tumor, and a leiomyoma with tubular structures. All of these lesions except for the epithelial component of the plexiform tumor showed ultrastructural characteristics of smooth muscle, demonstrating a common origin from the myometrium. Two tumors, the plexiform tumor and the leiomyoma with tubules, had the pattern of epithelial structures suggesting origin from müllerian mesenchyme: the plexiform tumor resembled incompletely differentiated endometrium and the tubular structures in the leiomyoma had features of mesothelium. We conclude that these varied and often confusing morphologic patterns reflect the capacity of uterine smooth muscle and stroma to undergo a wide spectrum of alterations including differentiation toward epithelial structures. Changes of this type occur in benign and malignant uterine stromal neoplasms and do not in themselves have prognostic significance. Am J Surg Pathol 4: 59‐74, 1980.

Prenatal diagnosis of harlequin ichthyosis

We report the successful prenatal diagnosis of ichthyosis in the fetus of a woman whose previous liveborn child was affected with “harlequin ichthyosis”. The fetal diagnosis was established through analysis of ultrasonographically guided fetoscopic skin biopsies. These biopsies showed premature hyperkeratosis, most marked around hair follicles and sweat ducts, and forming plugs of hyperkeratotic debris. These observations were in distinct contrast to those in control fetuses, whose epidermis consists of squamous epithelium only a few cells in depth with minimal keratinization.

Fatal gestational choriocarcinoma. Clinicopathologic study of patients treated at a trophoblastic disease center

We studied 31 autopsied cases of gestational choriocarcinoma encountered at the Northwestern University Trophoblastic Disease Center in the past two decades to learn if the clinical and morphologic aspects of these cases have been altered by therapy. These cases were analyzed for cause of death, distribution of tumor and histologic patterns in relation to the amount of chemotherapy. Tumor hemorrhage and/or pulmonary insufficiency were the most common causes of death, irrespective of the amount of therapy although other factors including drug toxicity, sepsis, and uremia led to death in six cases. The amount of chemotherapy generally did not affect the number or distribution of metastases. Histologically, nine cases showed extensive or complete necrosis. Eighteen of the remaining tumors had typical biphasic patterns, but four patients who received multiple courses of chemotherapy had atypical patterns with a marked predominance of cytotrophoblast and infiltrative growth. These atypical patterns do not appear to be a direct result of chemotherapy but may represent a more aggressive form of this tumor. This study shows that fatal gestational choriocarcinoma can have a variety of clinicopathologic features which reflect not only the biologic capabilities of the neoplasm but also the effects of chemotherapy and prolonged disease. Cancer 50:1833‐1846, 1982.

Gestational choriocarcinoma. Its origin in the placenta during seemingly normal pregnancy.

: Four new cases of primary choriocarcinoma arising in the placenta during a seemingly normal gestation were studied at the Trophoblastic Disease Center of Northwestern University. In each case the patient presented with disseminated metastases while carrying an intrauterine gestation with a normally developing fetus. All four placental primaries were small; three of the tumors were microscopic and found only after extensive sectioning. Histologically, these tumors all appeared to arise from the cytotrophoblastic cells covering the stromal portion of villi, and in some areas the involved villi retained a portion of normal investing trophoblast. This study shows that gestational choriocarcinoma unassociated with hydatidiform mole can have an early stage in which chorionic villi are present. The consistently small size of the lesions studied suggests that primary placental choriocarcinoma may frequently be overlooked or missed, and that choriocarcinoma possibly has its origin in the placenta more often than in retained or persistent trophoblast following pregnancy.

Cystic epithelial-stromal tumor of the seminal vesicle

A cystic tumor composed of atypical glands in a cellular stroma arose in the pelvis of a 49-year-old man. Two years later an identical tumor was again excised from the pelvis. Morphologic, immunohistochemical and ultrastructural studies indicate that this neoplasm arose in the seminal vesicle, possibly from a seminal vesicle cyst. The tumor did not involve the prostate gland, and immunohistochemical stains for prostate-specific antigen and prostatic acid phosphatase were negative. Ultrastructural study showed that both the glandular and mesenchymal components of the tumor recapitulated features of normal seminal vesicle, further establishing origin from this site. This tumor resembles the rare cystadenoma of the seminal vesicle, yet the cytologic atypia suggests low grade malignant potential. Following the second excision, the patient has had a disease-free interval of 18 months. Long term follow-up and recognition of additional cases is necessary to define the biologic potential of this unusual tumor.

Optically clear nuclei: An alteration of endometrial epithelium in the presence of trophoblast

Examples of focal clearing of endometrial epithelial nuclei associated with the presence of trophoblastic tissue have been oberved recently in our surgical pathology laboratories. These nuclear alterations were initially observed in endometria from first and second trimester spontaneous abortions, term pregnancies, and a uterus harboring choriocarcinoma. Subsequantly, an idencical change was seen in small foci of endometriosis removed during postpartum tubal ligation. The prominent vacualated appearance to the nuclei resembled, in some cases, the inclusions seen in herpesvirus infection, but electron-microsopic study showed that the nuclear clearing was due to replacement of normal chromatin by a network of fine filamentous material rather than herpesvirus DNA. A subsequent review of 200 conseutive first-trimested abortions found less-striking degrees of this change in 7% of cases. The endometrial nuclear clearning was focal; often the endometrium also contained cells which demonstrated the Arias-Stella reaction. The etiology of this type of nuclear clearing is not known, but the fibrils may represent a thread-like substructure of normal chromatin which forms as a result of hormal stimulation of edometrial epithelial cells.