Mastocytosis presenting as a skeletal disorder.

Mastocytosis is a rare disease of mast-cell proliferation with involvement of the reticuloendothelial systems including skin, bone, gastrointestinal tract, liver, lungs, spleen, and lymph nodes. Systemic mastocytosis is characterized by a combination of symptoms that relate to the mast cells' release of vasoactive substances, such as histamine. These symptoms include urticaria pigmentosa, flushing, syncope with hypotension, headaches, nausea, vomiting, diarrhea, and occasional bronchospasm. The diagnosis of mastocytosis is typically based on the presence of the characteristic extraosseus manifestations. A well recognized roentgenographic feature seen in 70-75% of patients with mastocytosis is diffuse osteolysis and osteosclerosis, affecting primarily the axial skeleton and the ends of the long bones. Rarely, the bony involvement consists of generalized osteoporosis, which may lead to pathologic fracture, or solitary lesions (mastocytomas) which may cause symptoms of localized pain. Four patients with previously diagnosed systemic mastocytosis had unusual skeletal lesions. Clinical and laboratory evaluation of these patients eventually led to the correct diagnosis of systemic mastocytosis. We report these four cases to emphasize the need for thorough evaluation of unusual musculoskeletal findings in association with extraosseus symptoms that are characteristic of mastocytosis. Knowledge of a wide differential diagnosis of unusual skeletal lesions should include systemic mastosytosis.

Morbidity and recurrence with modifications of radical vulvectomy and groin dissection.

Vulvar carcinoma has been managed in recent years with modifications of radical vulvectomy and groin dissection. Separate groin incisions, superficial inguinal lymphadenectomy, unilateral groin dissection, and wide excision have been utilized to reduce the morbidity of treatment. In this study, the surgical management of 82 patients with vulvar squamous cell carcinoma was reviewed in order to assess morbidity and risk of recurrence. A modification of radical vulvectomy and groin dissection was employed in 67 patients, while 15 patients underwent classical en-bloc vulvar and groin dissection. Wound complications of the vulva occurred in 1 of 12 patients undergoing hemivulvectomy, in 8 of 55 undergoing radical vulvectomy, and in 7 of 15 who had en-bloc vulvar resection and groin dissection (P = 0.01). Among the 46 patients undergoing bilateral groin dissection through separate incisions, groin breakdown, lymphocyst, and lymphedema occurred in 10 (22%), 7 (15%), and 7 (15%), versus 0, 1 (7%), and 2 (13%) of the 15 who had unilateral groin dissection. Modification of vulvar resection did not increase the risk of local recurrence. Groin recurrence developed in 2 of 15 patients who underwent en-bloc groin dissection and in 1 of 46 who underwent bilateral groin dissection through separate incisions. Two of 15 who had a unilateral groin dissection recurred in the contralateral groin. The risk of recurrence as well as morbidity following modifications of radical vulvectomy with groin dissection should be considered when planning treatment.

Early stage I carcinoma of the vulva treated with ipsilateral superficial inguinal lymphadenectomy and modified radical hemivulvectomy: a prospective study of the Gynecologic Oncology Group.

Although cure rates are high, the morbidity of radical operation for carcinoma of the vulva is substantial. Between 1983-1989, member institutions of the Gynecologic Oncology Group entered 155 patients in a prospective evaluation of modified radical hemivulvectomy and ipsilateral inguinal lymphadenecctomy for clinical stage I vulvar cancer. Only patients with neoplastic thickness of 5 mm or less, without vascular space invasion, and negative inguinal lymph nodes were eligible for this study. There have been 19 recurrences and seven deaths from disease among the 121 eligible and evaluable patients. Patients whose disease recurred on the vulva were frequently (eight of ten patients) salvaged by further operation. Five of the seven deaths due to cancer occurred among patients whose first recurrence was in the groin. Acute and long-term morbidity as well as hospital stay were each less than in the Group's previous experience in a comparable patient population treated with radical vulvectomy and bilateral inguinal-femoral lymphadenectomy. There was a significantly increased risk of recurrence but not death when compared with these same historic controls. Modified radical hemivulvectomy and ipsilateral inguinal lymphadenectomy is an alternative to traditional radical operation for these selected patients with stage I carcinoma of the vulva. The number of patients who experienced recurrence in the operated groin is of concern and may be attributable to the decision to leave the femoral nodes intact.

Endometrial carcinoma: the relevance of cervical cytology.

In patients with endometrial carcinoma, preoperative identification of poor prognostic factors is helpful in planning therapy. Extended surgical staging, including pelvic and periaortic node dissection, is indicated in patients with deep myometrial invasion or high-grade tumor, or when other risk factors for extrauterine spread are present. In this study, cervical cytology was reviewed in 86 patients with endometrial carcinoma, all of whom underwent surgical staging, to correlate the cytologic results with surgical and pathologic findings. Cervical cytology was normal in 20 patients (23%), whereas suspicious or malignant endometrial cells were present in 23 and 43 cases (27 and 50%), respectively. Suspicious or malignant cervical cytology was associated with deeper myometrial invasion (P = .011), higher postoperative tumor grade (P = .006), positive peritoneal washings (P = .012), and more advanced stage by International Federation of Gynecology and Obstetrics criteria (P = .024). When compared with patients with normal cervical cytology, those who had malignant endometrial cells had over twice the risk of deep myometrial invasion (67 versus 30%), twice the risk of grade 2 or 3 tumor (60 versus 30%), and three times the risk of positive peritoneal washings (33 versus 10%). Seventy-four percent of patients with malignant cervical cytology were stage IC or more. In contrast, 70% of patients with normal cervical cytology were stage IA or IB. Patients with endometrial carcinoma who have malignant endometrial cells detected by cervical cytology are at increased risk of having a deeply invasive, high-grade, advanced-stage tumor, and therefore are more likely to require extended surgical staging.

The risk of breast cancer after irradiation of the thymus in infancy.

It is well established that exposure to ionizing radiation during or after puberty increases a woman's risk for breast cancer, but it is less clear whether exposure to ionizing radiation very early in life is also carcinogenic. We studied the incidence of breast cancer prospectively in a cohort of 1201 women who received x-ray treatment in infancy for an enlarged thymus gland and in their 2469 nonirradiated sisters. After an average of 36 years of follow-up, there were 22 breast cancers in the irradiated group and 12 among their sisters, yielding an adjusted rate ratio of 3.6 (95 percent confidence interval, 1.8 to 7.3). The estimated mean absorbed dose of radiation to the breast was 0.69 Gy. The first breast cancer was diagnosed 28 years after irradiation. The dose-response relation was linear (P less than 0.0001), with a relative risk of 3.48 for 1 Gy of radiation (95 percent confidence interval, 2.1 to 6.2) and an additive excess risk of 5.7 per 10(4) person-years per gray (95 percent confidence interval, 2.9 to 9.5). We conclude that exposure of the female breast to ionizing radiation in infancy increases the risk of breast cancer later in life.

Treatment of breast cancer with segmental mastectomy alone or segmental mastectomy plus radiation.

A retrospective review of the outcome of treatment for primary, Stage I and II breast cancer with segmental mastectomy (SGM) alone or segmental mastectomy plus postoperative irradiation (SGM + RT) at four Rochester, New York, city hospitals is reported. Between January 1971 and March 1984, 99 women were treated with SGM and 146 with SGM + RT. Groups were similar regarding significant clinical and histologic prognostic factors; they differed, however, in that the SGM group was considerably older (means = 72) than the SGM + RT group (means = 56). Among SGM patients, local and total locoregional failure was 26.44 and 35.2%, respectively. Local and total locoregional failure (7.6 and 12.4%, respectively) was significantly reduced among patients treated with SGM + RT (p less than 0.0001). Among SGM patients, there was scant advantage in enlarging the extent of resection from local excision (29.5% local failure) to wide local excision (27.3%) to quadrantectomy (22.2%). Among women receiving SGM + RT, similar rates of local failure occurred among patients receiving local excision (15.5%) and wide local excision (12.5%). By contrast, only 2.8% of those receiving quadrantectomy failed. Results are viewed as supportive of findings of NSABP-B06. Findings suggest that SGM constitutes inadequate treatment of Stage I and II breast cancer. Locoregional failure rates of 30-40% may be reduced to around 10% with postoperative irradiation.

The pathology and biologic behavior of ovarian cancer. An autopsy review.

1. Widespread visceral and intestinal wall metastases are present in women dying with ovarian cancer. Intestinal wall invasion is commonly found at autopsy and is associated with bowel obstruction. Liver parenchymal replacement by metastases in more extensive than that in the lung, where most metastases have a subpleural location. Multifocality characterizes metastases in both of these organs. 2. Neoplastic lymphatic invasion is common. Lymphatic and blood vascular invasion are associated with an increased incidence of metastases in lymph nodes, small bowel wall, pancreas, lungs, ureter, and liver. 3. The mean survival time from diagnosis to death is less than 2 years. Both increasing neoplastic histological grade and clinical stage at diagnosis are associated with decreased survival time. 4. The most common causes of death are carcinomatosis, infection, or a combination of these processes. Sepsis, pneumonia, or both of these account for most of the fatal infections. 5. Bowel and ureteral obstruction constitute the most common forms of tumor-induced morbidity. The former process tends to be multifocal, involving the small and large intestines, and it is found during the disease course as well as at autopsy. Ureteral involvement is usually associated with hydronephrosis and is bilateral in approximately one fourth of the cases.

Primary adenocarcinoma of seminal vesicle presenting as bladder tumor.

A case of primary seminal vesicle carcinoma is described and is discussed in the context of current knowledge regarding the clinicopathologic features of this rare neoplasm.

Survival time, causes of death, and tumor/treatment-related morbidity in 100 women with ovarian cancer.

One hundred cases of ovarian cancer were studied at autopsy to determine the effect of morphologic and clinical factors on survival time, the primary cause of death, and tumor/treatment-related morbidity. The mean survival time was 19 months (0 to 174 months). Increasing neoplastic histologic grade and increasing clinical stage at diagnosis were each associated with decreased survival time. In grade I tumors, the mean survival time was 84 months; in grade II tumors, it was 18 months; and in grade III tumors, it was 12 months (P = .0008). Patients who presented in stage I or II had a better survival time (28 months) than those who presented in stage III or IV (15 months) (P = .02). The most common causes of death were disseminated carcinomatosis (48%), infection (17%), pulmonary embolus (8%), and combinations of infection and carcinomatosis (11%). In patients dying of infection, 43% had sepsis, 21% had pneumonia, and 25% had a combination of sepsis and pneumonia. Escherichia coli and Klebsiella were the most common pathogens identified postmortem. Intestinal obstruction (51%) and ureteral obstruction (28%) were the most common forms of tumor-induced morbidity. Bone marrow depression and resultant pancytopenia was the most common form of treatment-induced morbidity.

Distribution of disease at autopsy in 100 women with ovarian cancer.

Clinical and morphologic factors that affected the distribution of disease are described in 100 cases of ovarian cancer at autopsy. In addition to the expected pattern of pelvic and abdominal peritoneal spread, extensive visceral parenchymal metastases were seen: liver parenchyma (45%), lung parenchyma (39%), small and large intestinal wall (52% and 55%), lymph nodes (70%), pancreas (21%), ureter (24%), bone (11%), and brain (6%). Liver parenchymal metastases replaced more than one third of the liver in 25% of cases, whereas lung metastases always involved less than one third of the lungs. When intestinal wall invasion was seen, bowel obstruction was present more often (71%) than when only intestinal serosa was involved (30%). Lymphatic invasion was predictive of lymph node, small intestinal wall, pancreatic, and liver as well as lung parenchymal metastases. Blood vessel invasion was predictive of pancreatic and ureteral metastases. Clinical stage I at diagnosis was associated with high incidences of liver parenchymal (56%), lymph node (56%), lung parenchymal (44%), large intestinal wall (33%), and bone (33%) metastases. Thus, ovarian cancer has parenchymal metastases similar to other carcinomas in addition to its peritoneal spread. Lymphatic and blood vessel invasion is predictive of such involvement. Intestinal wall invasion predicts bowel obstruction.

Testicular abscess: diagnosis by ultrasonography.

We reviewed 8 cases of surgically proved testicular abscess with emphasis upon the ultrasonographic findings. The images were correlated with testicular anatomy and the pathological findings of abscess formation. In 3 of 8 patients undergoing serial high resolution ultrasound examinations a consistent pattern of testicular abscess was present 1 to 7 weeks preoperatively. In the remaining 5 patients preoperative ultrasound documented the presence of abscess. Recognition of the ultrasonographic appearance of testicular abscess should permit expedient surgical intervention.

The pathology of vulvar squamous cell carcinoma and verrucous carcinoma.

Squamous cell carcinoma is far more common than verrucous carcinoma in the vulva. The clinical and morphologic distinctions between these neoplasms are important to understand because of their contrasting biologic behavior and treatment. Both cancers present with symptoms of pruritus and a noticeable mass. On examination, both tumors commonly occur on the labia and are exophytic. If infection occurs in association with verrucous carcinoma, the resulting induration of the surrounding tissue as well as reactive regional lymph node enlargement may fool the clinician into making an erroneous diagnosis of advanced squamous cell carcinoma. In the 33 percent of cases in which a squamous cell carcinoma is flat and ulcerated, the gross distinction from verrucous carcinoma is easy to perceive. The microscopic analysis of squamous cell carcinomas should specify the neoplastic thickness, depth of stromal invasion, and presence or absence of lymphatic invasion since these parameters are important in predicting the probability of lymph node metastases in superficially invasive cancers. Verrucous carcinomas are thick neoplasms which may invade and compress the underlying stroma with "pushing" margins. It is therefore crucial to recognize the microscopic features of this well-differentiated squamous neoplasm in order not to mistake it for a squamous cell carcinoma which has the capacity to metastasize to inguinal lymph nodes. Human papilloma virus has been implicated in the development of both of these tumors. The treatment for verrucous carcinoma is wide local excision. Because recurrence may occur if the surgical resection margins are involved by the neoplasm, the pathologist must carefully evaluate these margins. It is important to note that recurrence of verrucous carcinoma connotes a poor prognosis. The treatment of a squamous cell carcinoma which is thicker than 2 mm or has a stromal invasion depth of more than 1 mm is vulvectomy and bilateral lymph node dissection. If the neoplasm is less than 2 mm in thickness, regional lymph node metastases have not been reported and lymph node dissection may not be necessary. The best treatment option is wide local excision and close follow-up. As our understanding of superficially invasive vulvar squamous cell carcinoma continues to evolve, however, these recommendations may change.

Fine needle aspiration biopsy in the evaluation of lymphoreticular tumors of the thorax.

The role of fine needle aspiration (FNA) biopsy in the evaluation of lymphoreticular disorders involving the lung and mediastinum was evaluated in a study of 16 cases from the authors' institutions. The cytologic material from these cases was reviewed, and the original cytologic interpretations were compared to the tissue diagnoses, with the overall accuracy of the cytologic interpretation evaluated. There were no false-positive diagnoses of malignancy in this series. A definite diagnosis of malignant lymphoma was most readily made in those cases in which the lymphoma was of the large-cell type. Small-cell and mixed large-cell and small-cell lymphoid proliferations were less able to be definitively interpreted, with pseudolymphoma presenting particular difficulty. The results support the conclusion that FNA biopsy can be useful in evaluating these lesions but also emphasize the fact that accurate diagnosis requires correlation of cytologic, clinical and laboratory data.

Pemphigus vulgaris and microinvasive squamous-cell carcinoma of the uterine cervix.

Although patients with disseminated pemphigus vulgaris may have involvement of the uterine cervix, such involvement is often detected only after vaginal discharge or bleeding. When a cervical smear is obtained, distinctive cytologic abnormalities may be observed; these may be attributed to the changes of pemphigus or to an associated reparative/inflammatory reaction. This study documents the first two cases of microinvasive squamous-cell carcinoma of the uterine cervix developing in association with uterine cervical pemphigus. The gross pathologic, cytologic and histologic features of these lesions are illustrated. The cytologic criteria that may be helpful in distinguishing between cells derived from microinvasive squamous-cell carcinoma and pemphigus of the uterine cervix are described.

Hypoxemia from right to left shunting through patent foramen ovale.

We report a patient with severe hypoxemia from a large (41%) right to left shunt through a patent foramen ovale after right ventricular myocardial infarction, and review 18 previous descriptions of patients with right to left shunting through patent foramen ovale. These shunts occur when right atrial pressure is elevated above left atrial pressure, or when the anatomic relationship of the interatrial septum to the inferior vena cava is altered. Since 15-35% of the population have a potentially patent foramen ovale, interatrial right to left shunting may occur more frequently than had previously been recognized, and should be considered in a differential diagnosis of hypoxemia.

The pathology of superficially invasive, thin vulvar squamous cell carcinoma.

Thirty-six cases of vulvar squamous cell carcinoma 5 mm or less in thickness were studied, and potential predictors of lymph node metastases were evaluated. Tumor thickness and depth of stromal invasion were measured. Inguinal lymph node metastases were present in six (17%) cases, all of which had primary neoplasms more than 3 mm thick. The most superficial lesion to have lymph node metastasis was 3.2 mm thick and had 1.6 mm of stromal invasion. Nonetheless, depth of stromal invasion of less than 3 mm was associated with statistically fewer lymph node metastases (7%) than that of neoplasms with 3 mm or more of stromal invasion (50%). Although lymphatic or blood capillary invasion was present in four (11%) cases, this feature had no statistically significant association with lymph node metastasis. There was no relationship between clinical stage, surface diameter, or histological grade of the lesion and lymph node metastasis. A significant percentage of cases had either carcinoma in situ (31%) or atypical hypertrophic dystrophy (19%) in the epithelium adjacent to the infiltrating carcinoma. Koilocytotic atypia suggestive of human papilloma virus infection was present in the adjacent epithelium in 47% of the cases. This study suggests that thickness of the neoplasm is a valid predictor for the presence or absence of lymph node metastasis in vulvar squamous cell carcinoma; it may be more useful than neoplastic depth of invasion in this regard.

The pathology of breast cancer in women irradiated for acute postpartum mastitis.

The gross and microscopic pathology of breast cancers in women irradiated for acute postpartum mastitis was compared to the breast cancers found in the sisters of the irradiated women. Fifty-one cancers in 50 irradiated women and 25 cancers in 24 nonirradiated women were examined. In considering the lesions in the two populations, the size, location, histologic type, histologic grade, inflammatory response, lymphatic and blood vascular invasion, nipple involvement, axillary lymph node metastases, and menopausal status at the time of diagnosis were statistically indistinguishable. The only parameter that was different in the two populations was the desmoplastic response to the malignant lesion (P = 0.04). The control population had more marked fibrosis within the cancers compared with the irradiated women. With the exception of stromal response, this study shows that breast cancer in irradiated women is similar in the parameters evaluated to breast cancer in a control population.